abstracts of the viith world congress

ABSTRACTS OF THE VIIth WORLD CONGRESS 283

1 EFFlCACY OF NAFAMOSTAT MESILATE AS A REGIONAL ANTICOAGULANT ON EXTRACORWREAL CIRCULATION

Nafamostat mesilate(FUT) is a synthetic serine proteases inhibitor with a shod life span in vivo. With its activity against coagulation, contact and complement systems, it has been applied as an ideal regional anticoagulant to extracorporeal circulation. In Vitro studies there were showed that FUT inhibited the C4a production.

*cg/ml of FUT inhibited C4a, and SCmcg/ml of FLIT inhibited both C3a and C4a during experiment direct hemoperfusion(DHP) in human.

FUT as anticoagulant was applied to 200 plasma exchange(PE) in 31 patients, and PE was safely performed in all cases.

m(10-40 mg/hr) was continuously infused during PE. Hemocron activated coagulation time(ACT), Celite-clotting time (CCT), PT, APV, thromboelastogram (TEG) were measured during PE. ACT and FT were not prolonged during PE in systemic blood. CCT and APTT were only prolonged in the extracorporeal circuit but in systemic blood. FUT concentrations in the device were 3-6 mcg/ml. There was no worsening of bleeding or bleeding tendency during and after PE.

with anion exchange fiber(AEF) was carried out on 19 jaundiced dogs given a choledocho-caval shunt. Clotting did not occur with 100 mg/hr of FbT and flow resistance to the column did not increase, though DHP through AEF could rarely be performed with a large amount of heparin.

Hajine Abe, Thorv Tani, Kenji Nurna, Yoshihiro Endo, Toyokazu Yoshjoka, Masashi Kodama 1st kpt. of Surgery, Shiga Univ. of Medical Scimce, Otsu, Shiga, Japan

DHP

3 SEPARATE CIRCULATION WITH AN ARTIFICIAL HEART (AFij FOR THE STUDY OF AH CONTROL.

hear t w a s made i n a goat. iliethod between l e f t atrium and descending ao r t a . Then the ao r t a w a s clamped completely a t the a o r t i c a-ch to separate the systemic c i r cu la t ion between upper a d lower ha l f body. i n t h i s condition, upper half body was perfused by the natural hea r t (W) and lower half body w a s perfused by AH. un je r t h i s c i r cu la t ion , AH flow w a s changed automatically by giving several dr iving condition u t i l i z i n g the computer. The hernodynamic parameters ( a r t e r i a l pressure (AP) of upper and lower half body, blood flow (BF) of upper and lower ha l f body, C W , etc . ) were measured also automatically with computer.

1)iiyper-output condition f o r the lower ha l f body was obtained i n t h i s experimental model,

2)no co r re l a t ion between t o t a l BF and CVP, 3)no co r re l a t ion between BF of lower ha l f body and

4)”Z of upper ha l f body w a s not so influenced by

5)-the co r re l a t ion between peripheral res is tance

The separate c i r cu la t ion with an artif icial AH w a s placed l i k e LVAD

After several weeks of survival

‘The following r e s u l t s were obtained;

:ieart rate,

the change of AH flow.

:PR) and BF w a s not so changed rernarkablly i n NH hut was c l a s s i f i e d i n t o several groups i n Ail by h e change of AH dr iving condition. [t was considered t h a t the PR did not indicate

onl:i the cha rac t e r i s t i c s of peripheral condition, but w a s influenced by cardiac function or AH drki ing condition. Y .%e, K . Imachi, T . Chinzei , K.Mabuchi , K.Maeda, K . tinaiishi, T.Yonezawa, 1.Fujim-a and K.Atsimi i n s t . of Med. Electro. , Faculty of Med., Univ. of Tok~o

2 RAPID IMPROVEMENT DF NERVE CONDUCTION BLOCK AFTER INTENSIVE PLASMA THERAPY IN GUILLAIN-BARRE SYNDROME( GBS)

On-line plasma f i l t r a t i o n has been used in the pa t i en t s w i t h dysimmune neurological d i seases . Under a standardized pro tocol , 7 GBS pa t i en t s were t r ea t ed 5 times in aweek, by using the Plas- auto 2500 system with ce l l ulose di ace t a t e f i 1 t e r s . T h e treatment plasma volume was about one patient’., plasma volume per s e s s ion . Se r i a l nerve conduction s tud ie s including compound muscle ac t ion poten t ia l ( C M A P ) and motor nerve conduction time(MCT) were car r ied out before and a f t e r plasma treatment.

The nerve conduction blocks i n 4 GBS pa t i en t s previously observed without plasma treatment were pe r s i s t en t over the period of 4 weeks from GBS onset. However, CMAPs in 3 o f 7 pa t i en t s with plasma treatment rap id ly increased t o 183, 275 and 155 % of nadi r value a f t e r the i n i t i a l t r e a t - ment within 14 days of onse t . Rapid improvement in c l in i ca l symptoms a l s o noted. Pe r s i s t en t nerve conduction blocks were demonstrated in the pa t i en t without any increase of CMAP a f t e r plasma t r e a t - ment. No s i g n i f i c a n t changes were observed i n MCT over the treatment period.

We suggested t h a t in tens ive plasma therapy can be t r i e d within 14 days of GBS onset and the increases of CMAPs a f t e r plasma treatment might be important t o make t h e appl ica t ion of f u r t h e r i n - tens ive plasma treatment. The r eve r s ib l e conduc- t i on blocks a f t e r plasma therapy might occurred a t the l imi ted demyelination of nerve f i b e r s .

Y.Abe, I.Ozaki, T.Sato, M.Baba, M.Matsunaga, K. Takebe, 5 . Nari t a . Natl Nishi-Sapporo Hosp, Aomori Prefec tura l Central Hosp, Hirosaki Univ School o f Medicine, Japan.

4 EXPERIMENTAL APPLICATION OF PERFLUOROCHEMICALS E?RTLSION BLOOD SUBSTITUTE FOR CARDIOPULMONARY BYPASS -MORTALITY RATE AND T O X I C I T Y I N LONG TERM OBSERVATION - Cardiopulmonary bypass(CPB) was performed in beagles in two ways of use of Perfluorochemicals (PFC) emulsion. Group A ( n = 6 ) : About 732 of the blood was removed before CPB. CPB was carr ied o u t under hi:h concentration of PFC emulsion. Removed blood was returned t o the beagle a f t e r CPB. Group B(n=5): A l l the b l o o d was mixed with PFC emulsion in CPB c i r c u i t without removing. CPB was carr ied out under r e l a t i v e l y low concentration of PFC emulsion. A l l the blood i n C P B c i r c u i t was returned t o the beagle. PFC emulsion in the c i r cu la t in? blood was retr ieved w i t h c en t r i fuga l blood sepa- r a t i o n . A l l beagle was t r ea t ed with 4mg/Kg B . N . of betamethasone before or a f t e r CPB.

The amount of PFC re ta ined i n beagles a f t e r autotransfusion was 2 0 ? 1 . 9 g / K g B.W. i n Group A and 23.4?3.3g/Kg B.W. i n Group B . Blood PFC concentration of Group R however was 2 2 % of t ha t of Group A a f t e r centr i fugat ion. Survival r a t e was 100% i n Group B while t h a t w a s 59% i n Group A . Yistopathological abnormality was noted in l i v e r i n Group A which was not i n Group R .

S e i j i Adachi, Hisateru Takano, Siroo Iwata, Hiroyuki Noda, Tetsuzo A’xutsu. National Cardiovascular Center, Osaka, Japan.

Artificial Organs, Vol. 13, N o . 4 , 1989

284 ABSTRACTS OF THE VIIth WORLD CONGRESS

5 THE DIAGNOSIS VALUE OF ELECTROMIOCRAPHY IN THE UREMIC NEUROPATHY

Carpal tunnel syndrome (CTS)and urp_mic neuropz thy (UN) are frequently observed in patients regular dialysis treatment (RDT). This study aims to evaluate the usefulness of the indexes used in an electromyography (EMG) laboratory.

Twentysix patients on RDT were studied : seven with sure diagnosis of CTS and nineteen random selected among our whole dialysis population.Nerve conduction studies were performed measuring:median motor nerve conduction velocity(MNCV) and latency (MML) ,ulnar motor nerve conduction velocity(UNCV) and latency(LML) ,perone21 motor nerve conduction velocity (PNVC),median and ulnar sensory nervous conductivity (MSNC,USNC).

Using Relative Operating Characteristic Analy sis the most accurate index of CTS was the MML : a cut-off at 4 msec gived 1004 sensitivity and89% specificity.In patients on RDT without CTS all the motor and sensory indexes were under normal range and correlated with age of patients but not with duration or kind of dialysis procedure.

the diagnosis of CTS was the MML. The UN gives a widespread nerve slowing that worsens with age of the patients, apparently not affected by dialysis treatment.

Agazia B..Nordio M.,Guarda L.,Lorenzi S.,LombiniC. Angoletta F.,Marchini P.,Saporiti E. Dept. of Nephrology - Civili Riuniti Hospital- Venice-City Center ITALY

on

In patients on RDT the most useful EMG index in

6 DEVKU)€”T AND PERFORMANCE EVALUATION OF A CONPACT DIRECT DRIVE PIMP

The major problems with the existing centrifugal pumps are: 1) leakage through the seal, thus requiring a magnetic coupling, 2) mechanical trauma to the red blood cells, and 3) thrombus formation. In consideration of these problems, a new compact centrifugal pump was developed by eliminating the magnetic coupling. The impeller was directly mounted to the motor shaft and a V-Ring was employed behind the impeller to face-seal between the pumping and the mechanical chambers.

In vitro study demonstrated no-leakage through the seal over a duration of 200 hours against total head of 120 d g with the flow rate of 8 L/min. As for hemolysis, various types of

straight-bladed, bended-bladed and solid types of 26 and 36 mm diameters were tested with bovine blood. The result showed that at low flow rate of 1 to 2 L/min, revolution number contributes more to hemolysis than the impeller shape. Among various impeller shapes, the semi-open, straight-bladed type of 36 mm diameter showed the most faborable result with hemolysis index of 0.05 over the flow rate of 1.5 to 8.0 L/min.

The in vitro results were also confirmed in the left ventricular assist expriments using animals. Long term in vivo evaluation continues to test the durability and anti-thrombogenicity. Takeshi Aizawa, Junichi Ninomiya*. Tasuku Shoji* Setsuo Takatani**, Yukihiko Nos&** R&D Center, Nikkiso Co.,Ltd.. Shizuoka, Japan. * The Department of Thoracic Surgery, Japan Medical School, Tokyo, Japan. ** The Department of Artificial Organs, Cleveland Clinic Fdn, USA.

impellers including semi-open, open,

7 THE EXPERIMENTAL STUDY OF ARTERIAL RECONST- 8 BILIRUBIN REMOVAL BY PLASMA PERFUSION IN RUCTlON WITH A PROSTHESIS MADE OF SHAPE MEMORY FULMINANT HEPATITIS PLASTIC. The characteristics of shape memory plastic (SMP) are as follows: the foundametal shape is fixed at first. when it is heated in a warm liquid, it becomes rubbery and the shape can be changed. When the new shape is then cooled, it Ilardens and is fixed in that shape. When the SMP is heated again, it returns its original shape. W e attempted to use SMP(polyurethane) f o r the procedure of reconstruction of vascular lesion. Two types of SMP devices were made. One had a fixed spiral shape, which was straightened, and the other w a s a mesh cylinder originally, which folded up to become slender. In an experiment in vitro. both devices were put into test tubes containing tap water and water of 50°C was added. Then the devices returned to their original shapes as expected. Next, an in vitro study was conducted using a canine. B o t h devices were bonded to the tips of catheters and inserted to the aorta from the distal artery. A 45-50°C physiological saline solution was injected from the catheter. Both devices obtained their original shapes in arterial lumem and so maintained blood flow, but the results varied due t o factors as the curvature of the vessel and the injection speed and volume of the hot water. These SMP devices will, if proved succesful in further reseach. be a favorable procedure for the treatment of arterial stenosis or aneurysm without using a large invasive method. Noritake Akaba, llisashi U jiie. Michio Kohno, PouichirouYasuda, Ken ji Sakurai The First Dep. of Surg. The Jikei University School of Medicine.

Conventional plasma exchange (PEX) has been performed for treatment of fulminant hepatitis (FH), however, the use of fresh frozen plasma leads some inevitable complications, such as serum hepatitis. Although hemoperfusion with charcoal column has also been inducted for treatment of FH, other complications have been reported such as a reduction of platelet, hemorrhagic tendency due to a large amount of heparin. Thus we examined the effect of plasma perfusion (PP) on FH.

In 17 patients with FH or hyperbilirubinemia, PP were performed with plasma flo AP08 (Asahi Med. Co.) as a plasma separator, and Bespore UPC 111 (n=28, J.M.S. Co.) or BR 350 (n=9, Asahi Med. Co.) as an adsorber. The mean treated plasma was 5.0 L. In 10 patients, 43 PEX were performed, in which 1.87 L plasma was replaced as a mean.

The removal rate of bilirubin was 28.5i2.2% by PEX (n=43, 20.7k1.2 mg/dl to 14.921.0), 36.623.1% by PP with Bespore UPC I11 (n=28, 26.323.4 to 15.851.71, and 41.5% with BR 350 (n=9, 31.3i2.5 to 18.7k2.51, respectively. The removal rate of amino acids was expressed as Fischer score which is considered to be an index of severity of FH, UPC 111 improved Fischer score moderately (1.820.2 to 2 . 4 ? 0 . 4 ) , in contrast neither BR 350 nor conventional plasma exchange improved it.

Bespore UPC 111 might be a powerful equipment for the therapy of fulminant hepatitis comparing with the conventional plasma exchange. Youichi Akai, Kaoru Tabei, Shigeyuki Takeda, >umiko Homma, Eiji Kusano, Yasushi Asano. Dept. of Medicine, Div. of Nephrology, Jichi Medical School, Tochigi, Japan

We concluded that plasma perfusion with

Artificial Organs, Vol. 13, No. 4. 1989

ABSTRACTS OF THE Vll th WORLD CONGRESS 285

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PERFORMANCE OF A COMPACT NUTATING CENTRIFUGAL BJLIOD PUMP (TEASPOON PUMP) Cc,nventional c e n t r i f u g a l blood pumps have drawbacks: i n f e c t i o n through s h a f t s e a l and blood desenera t ion on t h e s e a l and j o u r n a l bear ing . A c e n t r i f u g a l pump with a n u t a t i n g ( n o t r o t a t i n g ) i m p e l l e r , s o c a l l e d Teaspoon pump, can overcome t t , ese drawbacks. T h i s pump is al lowed t o have o r . 1 ~ one i m p e l l e r f o r i t s own mechanism. There- fctre, its pump e f f i c i e n c y and s p e c i f i c pumping p r e s s u r e were not s o h i g h . B u t i t is much i m - proved b y ou r f o l l o w i n g i n v e n t i o n s : (1) annular passage made b y s e t t i n g t h e c o r e p o r t i o n i n t h e pump room, ( 2 ) a cudgel i m p e l l e r , ( 3 ) s p i r a l wel l -contoured i n l e t passage, ( 4 ) well-contoured o u t l e t passage and d i f f u s e r . I n t h e pump room, r e c t i f i e d flow i s obta ined a s i f a p i s t o n (im- p e l l e r ) pushes blood i n an e n d l e s s c y l i n d e r (annular pump room), and t h e p r e s s u r e d i f f e r e n c e between o u t l e t and i n l e t is s u s t a i n e d by c e n t r i f u - g a l f o r c e of r o t a t i n g blood f low. A t p r e s e n t , hemolysis i n th i s pump is a l n o s t t h e same a s t h a t i n a r o l l e r pump. I n o r d e r t o f i n d t h e way t o much reduce hernolysis , s p a t i a l and cemporal f low measurement a r e being c a r r i e d o u t i n t h e pump: p r e s s u r e , f l o w v e l o c i t y , t u r b u l e n t i n t e n s i t y and f low v i s u a l i z a t i o n . For our hemolysis t e s t , w e use micro-dye-capsules ,as s u b s t i t u t e s of red blood c e l l , which a r e s e n s i n g e lements of i n - d u s t r i a l use . The r e l e a s e d d y e c o n c e n t r a t i o n i s wel l r e l a t e d t o shear s t r e s s i n t h e f low. For compactness, o u r n u t a t i n g mechanism being i n - s t a l l e d i n n e r s i d e o f t h e r o t o r of b r u s h l e s s DC motor, whole s i z e of t h e pump is about 6 cm i n diaineter and 6 cm i n l e n g t h . I t i s implantab le . Teruaki Akamatsu Dept. of Mechanical Engineer ing , Kyoto Univers i ty KyJto, Japan

CLINICAL BENEFIT OF NAFAMOSTAT MESILATE(NM) AS AN ANTICOAGULANT €OR EXTRACORPOREAL CIRCULATION(ECC)

NM, p r o t e a s e i n h i b i t o r , p roduces a n t i c o a g u l a t - i n g a c t i o n almost e n t i r e l y l i m i t e d t o e x t r a c o r p o r - e a l c i r c u i t by d i n t of i t s s h o r t h a l f l i f e (about 8 min) . To c l a r i f y t h e e f f e c t s of NM as a r e g i o n a l a n t i c o a g u l a n t f o r ECC, 184 r e g u l a r hemodialysis(HD ) acd 20 p lasmapheres i s (PP) p a t i e n t s w i t h hemor- r h a g i c compl ica t ions w e r e examined. Adequate dose (3Smg/hr) of NM i n f u s i o n d i d n o t e l o n g a t e t h e a c t i v a t e d c o a g u l a t i o n tirne(ACT) a t all i n t h e s y s - temic c i r c u l a t i n g b lood dur ing and a f t e r H D , how- e v e r , it prolonged ACT i n blood p a s s i n g through d i a l y z e r a s w e l l as h e p a r i n . Using NM, 98% of HD i n p a t i e n t s w i t h a c t i v e hemorrhagic foci could be completed w i t h o u t t h e e x a c e r v a t i o n of b l e e d i n g , wh.ile us ing h e p a r i n ( l o w dose o r r e g i o n a l hepar in- i z a t i o n ) , hemorrhage w a s d e t e r i o r a t e d i n 15% of H D . Hemostat ic time a f t e r t h e removal o f needle was shor tened i n NM compared t o t h a t i n hepar in . A ! j j .gnif icant ly l e s s e r amount o f r e s i d u a l blood i n d i a l y z e r w a s observed us ing NM. I n PP, similar effects of NM on t h e p a t i e n t s w i t h h i g h b l e e d i n g r i s k w e r e observed. Furthermore, NM made it p o s s i - b l e t o use t h e c a t i o n i c a d s o r b e n t s for plasma p e r - f u s i o n , which adsorbed a n i o n i c h e p a r i n and could n o t b e a p p l i e d under t h e a n t i c o a g u l a t i o n w i t h h e p a r i n .

recponal a n t i c o a g u l a n t for p a t i e n t s w i t h hemor- r h q i c compl ica t ion , and many t h e r a p e u t i c mater i - a l s become a p p l i c a b l e by t h e use of NM.

Taclao Akizawa, Fumiyoshi Nakayama, T a t e k i Ki taoka , Shcii.o Koshikawa Fu:li.gaoka H o s p i t a l , Showa U n i v e r s i t y Yo>:cihama, Japan

These r e s u l t s i n d i c a t e t h a t NM is very u s e f u l

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10 CALCIFICATION OF SYNTFETIC POLYMERS I N SERUM

C a l c i f i c a t i o n h a s been i d e n t i f i e d a s one o f t h e c a u s e s o f diaphragm f a i l u r e a s s o c i a t e d wi th long-term use of a r t i f i c i a l h e a r t . This s t u d y was concerned wi th t h e i n v i t r o c a l c i f i c a t i o n of s y n t h e t i c polymers i n c e l l - f r e e serum.

Porous samples prepared from polyure thane , s i l a s t i c r u b b e r , po lymethylmethacry la te , poly- a c r y l o n i t r i l e by s a l t - c a s t i n g method were immersed i n f r e s h bovine s e r a whose Ca and P l e v e l s were a d j u s t e d t o 10mg/dl and 7mgldl. changed every week, and t h e [Ca] and [PI changes were measured by a c o l o r i m e t r y method. A f t e r 6 weeks, t h e samples were s u b j e c t e d t o h i s t o l o g y , SEM,EDAX and atomic a d s o r p t i o n s t u d i e s .

A l l samples except s i l a s t i c showed c l e a r ev idences of calcium phosphate d e p o s i t s . The amount of t h e d e p o s i t was wel l agreed w i t h t h e amount of t o t a l r e d u c t i o n of Ca and P from t h e s o l u t i o n . which a r e v e r y c l o s e t o t h e v a l u e of hydroxy- a p a t i t e of 2.16. p r o t e i n s on t h e c a l c i f i c a t i o n , immobilized serum p r o t e i n s on polya l ly lamine coa ted g l a s s beads were immersed i n t h e serum. The p r o t e i n s were h e a t t r e a t e d a t 60 or80°C b e f o r e t h e immersion. Compared t o t h e non-heat t r e a t e d p r o t e i n s , t h e hea ted samples showed enhance3 minera l d e p o s i t s .

T h i s s t u d y sugges ted t h a t c a l c i f i c a t i o n could t a k e p l a c e through t h e mechanism b e s i d e s d y s t r o - p h i c type . i n f l u e n c e on t h e c a l c i f i c a t i o n p r o c e s s . Michhide Aki ta , Shun Murabayashi, Toshiyuki Shimooka, and Toshio Yuhta Department o f Biomedical Engineer ing The U n i v e r s i t y of Hokkaido, Sapporo, Japan

The s e r a were

The Ca/P r a t i o s ranged from 2 . 0 t o 2 . 4 ,

To s t u d y t h e e f f e c t of adsorbed

The adsorbed p r o t e i n s may have some

12 UNSTEADY FLUID DYNAMICS OF THREE CONTEMPORARY HEART VALVES USING A TWO COMPONENT LDA SYSTEM

The paper p r e s e n t s r e s u l t s of an ex tens ive tes t program aimed a t s teady and t r a n s i e n t measurement of p r e s s u r e drop, v e l o c i t y p r o f i l e s , turbulence i n t e n s i t y , viscous and turbulen t shear stresses and t h e i r decay i n the wake of t h r e e mechanical t i l t i n g d i s c type h e a r t va lves of c u r r e n t i n t e r e s t (Bjork-Shi ley convexo-concave, Bjork-Shiley Monostrut. and B i c e r - V a l ) . The s tudy was c a r r i e d out us ing a s o p h i s t i c a t e d and versati le c a r d i a c s imula tor i n conjunct ion w i t h a h ighly s e n s i t i v e , noninvasive, two-component three-beam l a s e r doppler anemometer system. The i n v e s t i g a t i o n covers both t h e s teady (valve f u l l y open) and p u l s a t i l e flow c o n d i t i o n s over a range of frequency represent ing rest and e x e r c i s e condi t ions . The cont inuous monitor ing of parametr ic t i m e h i s t o r i e s revea led u s e f u l d e t a i l s of t h e complex f low as w e l l as helped e s t a b l i s h l o c a t i o n and t iming of t h e peak parameter va lues . Although each of t h e va lves t e s t e d showed some s i m i l a r i t y with t h a t of an o r i f i c e j e t f low, t h e i r d e t a i l e d c h a r a c t e r d i f f e r e d markedly as r e f l e c t e d i n t h e pressure , v e l o c i t y , tu rbulence i n t e n s i t y and shear stress r e s u l t s . Based on t h e nondimensional p r e s e n t a t i o n of the d a t a , t h e fol lowing genera l conclusions can be made : ( i ) The d ischarge c o e f f i c i e n t is dependent upon t h e Reynolds number. ( i i ) The va lves t e s t e d showed r i s e i n turbulence i n t e n s i t y by as much as a n order of magnitude p r e s e n t i n g a p o s s i b i l i t y of thromboembolism and, perhaps, hemolysis. ( i i i ) Back f low c h a r a c t e r dur ing the c los ing phase is s i g n i f i c a n t l y a f f e c t e d by t h e maximum open a n g l e , which is d i f f e r e n t f o r t h e valves t e s t e d .

T. Akutsu and V.J. Modi F a c u l t y of Applied s c i e n c e U n i v e r s i t y of B r i t i s h Columbia, Vancouver, B. C. , Canada



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THERAPEUTIC ON-LINE LEUKOCYTE REMOVAL FOR RHEUMATOID ARTHRITIS(RA)

A new technique , on-l ine f i b e r f i l t r a t i o n , was appl ied f o r R A with t h e Imguird (Terumo, J a p a n ) , made of gossypium barbadense c o t t o n . This procedure can be done s imply , s a f e l y a t a low blood flow r a t e ( 2 0 ml/min) and needs a smal l ex t racorporea l volume. F ive p a t i e n t s with RA were designed t o be t r e a t e d weekly f o r 4 t imes and monthly t h e r e a f t e r . A 1200 m l of blood was processed for each t rea tmen5 us ing two I u g u i r d s , an gverage of 5.3+0.7X10 , l.gi 0.7X10 , +O. 3x10 , 3.7+O.4X1O9, 1.4+1.4X10 , 4.6+2 .0X18io-of leukocytes , lymphocytes, bands, n e u t r o p h i l s , monocytes and p l a t e l e t s were re - moved. Removal r a t e s of p l a t e l e t s and a l l leuko- c y t e s except lymphocytes (80%) were high (85- loo%), among them monocytes h i g h e s t .

P o s t leukocytes counts obtained from t h e pa- t i e n t s were not reduced compared with t h e pre t rea tment v a l u e s , while p l a t e l e t s count was reduced (14%). S t a t i s t i c a l l y s i g n i f i c a n t i n c r e a s e s a f t e r t rea tment were seen i n ConA lymphocyte mitogen s t i m u l a t i o n (LMS) and decreases i n t h e % of Leu7. No s i g n i f i c a n t changes were noted i n t h e % of OKT3, OKT4, OKTB, OKIal, OKM1, O K T 1 1 , O K B 7 and i n PHA LMS. Plasma l e v e l s of immuno- g l o b u l i n s and rheumatoid f a c t o r were a l s o reduced. Over t h e course , however, no c o n s i s t e n t changes were observed i n a l l chemical and immuno- l o g i c a l parameters t e s t e d . The change of d i s e a s e a c t i v i t y began dur ing t h e f i r s t 4 s e s s i o n s , without causing leukopenia or lymphopenia. Kuniki Amano, Michinori Imazu*, Haruo Ezaki Department of Surgery , Department of I n t e r n a l Medicine*,Kitakyushu General H o s p i t a l , Fukuoka, Japan

4

NEW TREATMENT FOR ENWTOXXMU WITH POLYMYXIN B IlrPlOBILIZED FIBER

In sp i te of the intensive therapy, t h e mortality r a t e of endotoxic(ET) shock is still high. W e thought t h a t removal of ET from the blood would be one of the most effect ive treatment. Recently W e have developed the material i n w h i c h polymyxin B is imnobilized t o polystyrene f iber (PMX-F) for detoxifying endotoxin. In v i t r o study, we examined whether chemical mediators (TNF and cytokines, TxB2, PGF52, PMN-elastase, et a l . ) w e r e adsorbed by PMX-F. Fndotoxin adsorbed w e l l in batchwise system, however chemical mediators were not adsorbed. W e atenrpted t o evaluate t h e efficacy of PMX-F using direct herno-perfusion (DHF') for endotoxic animals. W e a l so compared with t h e efficacy of activated charcoal and a f iber of pre-attachment of Polymyxin B a s a control (Carrier f i b e r ) i n detoxyfying ET. There w e r e differences of BP response between PMX-F group and other adsorbent groups, A l l groups showed imnediate severe drops i n WBC and Pl ts . Charcoal group survival r a t e was 20 7, Carrier groups survival r a t e was 0 % whereas PMX-F groups survival r a t e was 73 $. In c l i n i c a l me, DHF'with PMX-F was performed safely f o r 2 h. Pla te le t s counts w e r e decreased during DHF', but they recovered by 24 h i n numbers. The another blood compatibility of PMX-F in c l in ica l use showed f a i r y good. W e a l so report t h e action m e c h a n i s m of PMX-F t o m e the endotoxin shock animals. W e thought t h a t endotoxic animals cured by adsorption of endotoxin.

Hirohiko Aoki, Thoru Tani, Toyokazu yosioka, Kenji Numa, Masashi Kodama 1st Department of Surgery, Siga University of Medical Science, Seta, Ohtu, Japan

14

16

EFFECT OF BLOOD LEUKOCYTE CONTAMINATION ON COMPLEMENT CICTIVATION STUDIES

Two mixtures composed of 10 red c e l l s and 10 f resh frozen plasma u n i t s were perfused with a RAPID INFUSION SYSTEM (HAEMONETICS). The f i r s t one i s made of standard red c e l l s and has a leukocyte contamination of 5.3 109/l . The second i s made of red c e l l s u n i t s buffy-coat depleted and f i l t e r e d with a SEPACELLR(ASAHI) (2 10' leukocytes per l i t e r 1 .

Complement f rac t ions were tested by immuno-nephelemetry before and a f t e r infusion a t 1500 ml/min.

g/l leukocyte-rich leukocyte-poor b e f o r e after before after

C3c 0.592 0.363 0.374 0.371 C 4 0.18 0.12 0.12 0.12 C l q 0.073 0.053 0.049 0,054 FB 0.195 0.098 0.104 0.104

Leukocyte contaminated mixture has higher i n i t i a l l eve ls for a l l f rac t ions and a marked consumption during infusion . It may have implications f o r bio-compatibi l i ty studies and adverse reactions t o massive blood tr ansf us i ons.

M . A ~ ~ ~ ~ 1 , M.Guiguet , M.Freisz M. T. Noi r ot3, B. Let ourneaus , P. Chat e l a i n Blood center*departement of biochimics2 and anesthesiology , D i j o n , FRCINCE

A STUDY OF BONE GLA PROTEIN AND HYDROXYPROLINE I N THE BLOOD OF CHRONIC HEMODIALYSIS PATIENTS

Purpose and method; Bone G l a P r o t e i n (BGP) and hydroxyprol ine were measured i n t h e blood of 114 chronic hemodialysis p a t i e n t s by t h e R I A and HF'LC methods. The v a l u e s obta ined i n t h e s e s t u d i e s were t h e n compared w i t h bone metabolism parameters t o determine i f e i t h e r o r b o t h of t h e s e methods could be used a s bone metabolism markers.

Results; The b lood BGP and h y d r o m r o l i n e both demonstrated h igh v a l u e s ; 36.6+25.0ng/ml and 5.05 +2.561-lg/ml, r e s p e c t i v e l y .

A s i g n i f i c a n t c o r r e l a t i o n was demonstrated between BGP and hydroxyprol ine.

BGP and hydroxyprol ine both demonstrated a p o s i t i v e c o r r e l a t i o n t o PTH-C and ALP.

A n e g a t i v e c o r r e l a t i o n w a s shown between BGP and b o t h t h e M C I and cGS/D of t h e bone of t h e 2nd f i n g e r . A n e g a t i v e c o r r e l a t i o n was a l s o shown between hydroxyprol ine and zGS/D.

b o t h BGP and hydroxyprol ine and t h e R I uptake r a t i o , i . e . , t h e count r a t i o between bone s c i n t i - graphy counts ob ta ined i n R O I p l a c e d i n b o t h t h e lumbar s o f t t i s s u e and t h e t h i r d lumbar bone of t h e s p i n e .

Conclusion; BGP and hydroxyprol ine were both shown t o b e important bone metabolism markers which demonstrate t u r n over i n hemodialysis p a t i e n t s .

A p o s i t i v e c o r r e l a t i o n w a s demonstrated between

Tadashi Aoki , Hisao Mabuchi , Hisamitsu Nakahashi Hemodialysis U n i t , N i s h i j i n H o s p i t a l , Kyoto, Japan

Artificial Organs, Vol. 13, No. 4, 1989

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19


UIMPARISGN OF THE COAGULATION TESTS TO ADJUST DOSAGE OF LOMMOLECULAR WEIGHT H E P A R I N ( L M F ) OR UNFRACTIONATED H E P A R I N ( U F H ) DURING HEMODIALYSIS.

Coagulation t e s t s were ca r r i ed out t o examine the minimal requirment of heparin dosage during hemodialysis ( H D ) . The sub jec t s were 2 2 pa t i en t s with chronic renal f a i l u r e . Coagulation time (CT), ac t iva ted coagulation time ( A C T ) , ac t iva ted p a r t - i a l thromboplastin time ( A P T T ) , f ac to r X a c t i v i t y ( X a ) , thrombelastography (TEG) and plasma heparin concentration were examined. Samples were obtained from th ree points of the extracorporeal blood c i r c u i t (A l , A 2 , V; pre- and post-heparin infusion l i n e and post d i a l y z e r , respec t ive ly) during HD. Dialyzer c l o t t i n g was minimal when the reaction time on TEG (TEG-r) w i t h samples from V but n o t from A1 o r A2 kept longer than 20 min in the case redusing dosage of e i t h e r LMH o r UFH. CT, ACT, APTT and Xa w i t h samples from Al, A 2 and V were n o t s e n s i t i v e encugh t o a d j u s t dosage o f L M H . Peasurement of plasma heparin concentration required too much time f o r heparin monitoring.

Ide conclude t h a t TEG-r usino samples from V i s the most s u i t a b l e and convenient t e s t t o minimize dosage o f b o t h LMH and U F H .

Hideo ARAKURA, Toshio lim , Masafumi KATAKURA, Nsomi KATO, Toshihide SHIROTA, *Seinosuke NAKAGAWA Shinshu University Hospital , Katsumoto, Japan and *Tokyo Metropolitan Tama Ger i a t r i c Hospital , Tokyo, Japan

A NEN lQTHO3 FOR ASSESSING CARDIAC E " I 0 N DURING ASSISW CIRCULATION To evaluate the recovery of an ischemically

injured heart and determine the optimal timing for weaning from ventricular assist device(VAD) without harniful interventions to the failed heart, we developed a new method for assessing cardiac pump function which is sensitive to changes of either inotropic state or ventricular compliance. ?'i-re index, which is derived from the time-varing ventricular elastancs model reported by Suga and Sagawa, is the ratio of -+ale left ventricular (LV) pressure (pmax) of an isovolumic contraction beat t.o end-diastolic pressure(Ped) - It can be obtained from a single beat without changing any loading conditions of failed hearts during assisted circulation. In 14 open chest dogs, a micromanometer was inserted into LV to measure intracavitary pressure. hnax/Ped was obtained from an isovolumic contraction beat created by clamping the ascending aorta. Dopamine was infused to alter the inotropic state and pericardiurn was opened to improve ventricular compliance. Pmax/Ped was changed as follows:

Control intervention p Dopamine(n=6) 19.00 .0 28.6+12.6 (0.02 Pericardium(n=8) 33.5k6.2 43.8i9.8 (0.01 These results suggested that Pmax/Ped was the

,ndex which was sensitive to changes of both vmtricular contractility and compliance. 'herefore, WB conclude that this index, which .requires only ventricular pressure measurements, !weins to be useful in monitoring cardiac pmj, E-mction of failed hearts assisted with VAD. ._ T.Asou, M.Oe, K-Fukamachi, K.Kishizaki, F.Fukumura I<.Tokunaga. Dspt. Cardiovasc. Surg. Kyushu Univ. ? k u o k a , JAFFAN.

18

20

EXPERIMENTAL AND CLINICAL STUDIES ON THE SI(;NIFICANCE OF PLASMA EXCHANGE FOR INTRACTABLE JAWICE The significance of plasma exchange for

intractable jaundice was assessed with special reference to the mitochondria1 respiratory function of the liver. Obstructive iaundiced mdel was created usins

E x p r imental studies

rats by the ligation of bile duct. 3 weeks later, the respiratory function and morpholqy of the heptic mitochondria (Mt) were comparatively evaluated between Mt directly fractionated from liver tissue (namely, Mt-A) and Mt fractionated from hepatccytes obtained by Seglen's methd (Mt-B) for elimination of respiratory inhibitory factors around M t Of Mt-A, ATP synthesis decreased to 75% of the

control at 1 and 2 weeks, and 58% at 3 weeks after ligation. On the contrary, it was 97%, 33% and 07% of the Control at 1,2 and 3 weeks in Mt-€3. By electron microscope, the size of Mt-A is inconsistent and smaller than that of Mt-&

One, 2 &d

_ _ ~..

Clinical stuay 50 y/o male suffered from Dostowrative benicm stricture of the hepatic duct after right hemihepatectomy for hepatic trauma. Although 100 - 200 ml of bile per day was obtained by PTBD, the jaundice deteriorated and plasma exchange was introduced 6 months after operation when total bilirubin concentration became 20mg/dl. A total of 116 times of chronic plasma exchangehas been performed for 4 years. Plasma exchange that removes respiratory

inhibitory factors can maintain mitochondria1 function in intractable jauradice. Y. Asanuma, K. Koyama, K. Suzuki, S. Omokawa, H. Andoh, S. Miyagata*, T. Harada* Department of Surgery, Urology*, Akita University, Akita, Japan

THERAPEUTIC PLASMA EXCHANGE IN PEDIATRIC DISEASES

Therapeutic plasma exchange (TPE i s known t o be benef ic ia l i n d i f f e r e n t severe d i s e a s e ' j n adu l t s and i n ch i ldren , too. By using an adequatc TPE system w i t h a very small extracorporeal volume and small blood flow, it i s poss ib le t o t r e a t even premature in fan t s and newborns with TPE.The complications depend from TPE a r e the same l i k e in adu l t s .

We repor t our experiences with TPE in 46 i n - f a n t s and 22 newborns. In t o t a l 556 TPE-treatments were performed i n 68 ch i ldren with an age between 1 day and 16 years . As an addi t iona l therapy, TPE was used i n 17 d i f f e r e n t d i seases : Hemolytic uremic syndrome (n=13) , acu te myolysis ( n = l ) , r ap id progressive glonierulonephritis (n=3) Typ I d iabe tes (n=4) , acu te +epa t i c f a i l u r e (n=5) hemolysis, immune hemolytic Anemia (n=3) , apla- s t i c anemia ( n = 2 ) , acute/chr:mic id iopa th ic thrombocytopenia ( n = 5 / 1 ) , Rh-incompatibil i ty (n=7) , Endotoxin-shock, s eps i s (n=9) , systemic lupus erythematosus (n=5) , nwrosarkoma ( n = 2 ) , drug in toxica t ions ( n = 4 ) , Re,fe-syndrome ( n = 2 ) , Burns ( n = 2 ) . With average of 8.1 TPE-treatments per pa t i en t , 39 ch i ldren (57.4 %) improved, 12 ch i ldren (17.8 % ) showed only a temporary irnpro- vement and 1 7 pa t i en t s (25 %) died desp i t e inten- s i v e TPE.

Besides the c l i n i c a l courses, r e s u l t s and the management of TPE i n ch i ldren and newborns with technical aspec ts and complications a r e reported.

R . Bambauer, R . ET-Saadi ,N. Graf ,H. J . Jesberger , H.G.Limbach,F.C.Sitzmann,U.Keuth,Facul- typ of Med., Univ.of Saarland. Homburg/Saar, FRG

Artificial Organs, Vol. 13, No. 4 , 1989


21 THERAPEUTIC PLAStlA EXCHANGE AND HEMODIALYSIS IN SEVERE BURNS

1988, our University hospital received 47 burned pa t i en t s . In 41 pa t i en t s t he mean t o t a l body sur face area (TBSA) burn was 18 % they were t r e a - ted conservatively and su rg ica l ly . S ix pa t i en t s were t r ea t ed with therapeut ic plasma exchange ( T P E ) and hemodialysis ( H D ) da i ly . The mean TBSA of these 6 pa t i en t was 66 % (range 45-92 2,). All 6 pa t i en t s developed a hypernatriemia of 153+3.6 mmol/l, an acute renal f a i l u r e (Crea t . 3.5+1:4 mg/dl, Urea 137.6223.4 mg/dl ) , a severe disseminated in t ravascular coagulation and an acute resp i ra tory d i s t r e s s syndrome.

ween 1 and 2 1 times. One pa t i en t w i t h a TBSA o f 92 % died two days l a t e r . Three pa t i en t s died one, 2 and 4 weeks a f t e r the a i r d i s a s t e r and two pa t i en t s improved. Before each treatment blood samples f o r endotoxin and endotoxin binding capac i ty were taken. The endotoxin concentration varied extremely but decreased s i g n i f i c a n t l y under TPE. The management and the course o f t he six burned pa t i en t s a r e reported.

After the Ramstein a i r d i s a s t e r i n Aug. 28,

The 6 pa t ien ts were t r ea t ed with TPE and H D bet-

R.Bambauer, U.Weber, J.Wi t t l ing, O.Trentz, Faculty o f Medicine, University of Saarland Hornburg/Saar, FRG

23 EYES AS BRAIN MIRROR DURING EXTRA-CORPOREAL CIRCULATION.

It is well known that ocular modifications give a hint about cerebral modifications. Ocular modifications were studied before, during and after extracorporeal circulation (ECC) in 2 3 patients (using or bubbles or membranes oxygenators with or without arterial filters). The study concerned the mesure of visual acuity (I.0ng and short distance), ocular fundus, skiascopy, visual field, fluoresceine angiography.

The results showed an anemia of the ocular fundus at the start of ECC (complete dilution). The intensity of the anemia observed was dependent of the rapidity of the start of the ECC.

Other results did not show any significant modifications before and after ECC. We can conclude that progress in technics mate-

rials used, solutions and drugs perfused and anesthesia allows actualy a surgical ECC without any ocular, and we thing, brain problems for the patient.

R. BARTHELEMY, CH. POMES, P. BEC. Service de CHIRURGIE CARDIO-VASCULAIRE CHU RANGUEIL, 1 avenue J. Poulhhs. 31054 TOULOUSE Cedex . nr &

22 THE IMPACT OF ECOLOGY ON AFRICAN NEPHROLOGY

The practice of modem nephrology in Africa is modified by ecological factors that frequently have different impacts in other parts of the world. In this report. the data obtained from several studies are analysed to give a conceptual overview of the topic. The aetiological profile of renal disease is largely modified by endemic diseases including parasitic (schistowmiasis, malaria), bacterial (streptococci. M. tuberculosis) and V i r a l (HBV, HIV, EBV) infections. The clinical pictures are vitiated by the effects of associated nutritional deficiencies and environmental pollution. Socioeconomic factors have a considerable impact on renal replacement therapy. Certain methods are either impossible or extremely limited (CAPD, home Dx, cadaver Tx). Others are inappropriately used (un- related donor Tx). Rehabilitation of dialysis patients is limited by inadequate therapy (lack of funds, shortage of equipment. poor compliance) and associated infections. Immunosuppression for renal Tx is associated with a high risk of infection. largely dominated by bacterial (tuberculosis. salmonellosis) rather than viral and fungal diseases. Although HBV is common, its contribution to morbidity and mortality is modest. The impact of CMV is not clearly defined. The potential of oppor- tunistic parasites (Pneumocystis and Toxoplasna) is limited.

The interaction of vqious abiotic and bio-ecological factors has considerably chaqged priorities, strategies and applications of modem Nephmlogy in Africa. Aware- ness of such factors in local communities is essential for planning and optimal practice. RASHAD S. BARSOUM RENAL UNIT. CAIRO UNIVERSITY CAIRO, EGYPT.

24 A NEW KIND OF FUhP BASED ON FEHJiOFLUID FOK T.A.H. A.ND ASSISTED CIRCULATION: F I R S T EXPEHIhXNTAL DATA

The Author presents a new kind of

electromagnetic pmp based on Ferro-

fluid (U.S.A. Patent no 4,650,485 and

other patent application pending). Ihe

p m p has a very simple design, a rigid

external she l l and no rotating part.

The membrane’s resistence to fatigue

is improved and red blood cell’s damage

is reduced owing to the soft ejection

mechanism.

In 198& a first prototype has been set

to work in a mock circulation. Experimental data will be presented.

DELLA SALA BERARDINO

Ospedale S a n Carlo Borromeo Divisione Chirurgia 7 O Piano Via Pi0 11, no 3-BBilano- ITALP

Artificial Organs, VoI. 13, No . 4, 1989


25 OESERVATIONS Ch' THE CARDIAC ACTIONS OF SFHS AND PERFLUOROCARBOF PPFIFARATIONS.

Strnma-free hemoglobin (S.F.H.S.) i n s o l u t i o n was prepared by t h e " c r y s t a l l i z a t i o n " (SFHSL) and i!J t r a f i l t r a t i o n (SFRS21 methods. The phosphol ip id c n n t e n t of t h e s e p r e p a r a t i o n s i s 4.6421.C2 and 0.741'0.20 pMole/ml, r e s p e c t i v e l y . The p r o t e i n composj t ion a l s o d i f f e r s somewhat. The c a r d i a c a c t i o n s of t h e s e p r e p a r a t i o n s were a s s e s s e d by pulse- infus i0r . s i n i s o l a t e d Langendnrff-perfused r a t h e a r t s a t c o n s t a n t f low. SFHSI induced c o n s i s t e n t l y g r e a t e r coronarv v a s n c o n s t r i c t i o n than SFIISZ; t h e former a l s o w a s found t o c o n t a i n a p r o t e i n p a r t i c d a t e m a t t e r which, when removed, reduced v a s o c o n s t r i c t i o n s u h n t a n t i a l l y . F r a c t i o n a t i o n procedures i s o l a t e d most o f t h e v a s o c o n s t r i c t o r a c t i v i t y t o f r a c t i o n s c o n t a i n i n g most of t h e hemoglobin. I n a d d i t i o n , v a r i o u s b a t c h e s were found t o d e p r e s s t h e c t m t r a c t i l j t y of t h e s e h e a r t s , t o v a r i a b l e e x t e n t s . The contractiljty-depressant ac t iv ' tv w a s a l s o found t o b e a s s o c i a t e d w i t h t h e same f r a c t i o n , b u t l e s s cons!s ten t ly .

Per f?uoro-oc ty lhromide w a s a l s o t e s t e d i n h e a r t s ; i t reduced coronary blood f low, i n roughlv i n v e r s e p r o p o r t i o n t o t h e e x c e s s oxygen p r e s e n t i n t h e PFC-phase. A t e q u i v a l e n t myocard ia l oxvxen d e l i v e r y - r a t e s (coronarv f low x oxygen c o n t e n t ) , c o n t r a r t i l i t v was s u b s t a n t i a l l y g r e a t e r i n t h e p r e s e n c e of PFOB t h a n i n i t s absence . l suppor ted bv t h e D . C . I . E . M . of Canada apd A l l i a n c e Pharm. Corp. , La Mesa, CA 92041, U.S.A.] C . P . R i r o , M. Lang, P . J . Anderson, Dept . of Phys io logy , U n i v e r s i t y of Ottawa, O t t a w a , Canada KLY 8M5.

27 USt,: HFPATOCYTES CULTURED ON MiCROCARRIERS FOFf -,,,,. i n c 2 A T M E N l OF C C i --INDUCED HEPATIC FAILUHE I N RATS

Fulminant h e p a t i c f a i l u r e ( F i i F ) i s a s e - r i o u s c l i n i c a l syndrom wi th a high l e v e l of m o r t a l i t y . Here w e r e p o r t t h e a r t j f i c i a l l i v e r siipporr system (ALSS) based on h e p a t o c y t e s c i i i t i i red 011 aiosi ion m i c r o c a r r i e r s . Under t h e s e c o n d i r i o n s - t h e den i t y of c u l t u r e d c e l l s was i.0-i . 5 x 1 0 5 cel ls /cm' and hepatocytes were a b l e to s y n t h e s i z e 20-30 ug albiimin, 4-6 u g f i b r o n e - c t i n and 2-4 ue f i b r i n o g e n per i06 c e l l s a t 24 hours f o r a t l e a s t 5 d a y s .

Experimetns were performed i n Wistar r a t s w i t h FHF induced by i . p . a d m i n i s t r a t i o n of 7% CCL in a dosage of 2 . 5 ml/kg body weignt . The devt iopment of FHF was accompanied by an i n c r e - a s e j n serum i e v e l s of LDR ( 8 0 - f o l d ) , GOT (130- f o i d ) , GPT ( 2 0 0 - f o i d ) . GLDH ( 4 0 - f o l d ) , b i i i r u - b in ( 3 . 6 - f o l d ) and a d e c r e a s e i n c h o l i n e e s t e - r a s e by 35%. 48 tiours a f r e r C C i 4 i n j e c t i o n a l l an imais d i e d . T h i s model of FHF has been iised f o r t h e e v a l u a t i o n of o u r ALSS. Rats were sub- j e c t e d t o e x t r a c o r p o r e a l hemosorbtion v i a m i n i - columns c o n t a i n i 2 ml of R i o s i l o n microcar- r i e r s wich 40x10Egcul tured h e p a t o c y t e s . The procedure was performed 20-24 h a f t e r CC14 i n j e c t i o n and l a s t e d f o r 3 h a t a f low r a t e cf 60 ml /h . T h i s reduced m o r t a l i t y from 100% t o 20% a f t e r 48 h and t o 40% a f t e r 96 h of t h e cievelopment of FHF.

O u r r e s u l t s s u g g e s t t h a t hepa tocytes c u l t u - red on m i c r o c a r r i e r s may be e f f i c i e n t l y app- j j e d t o c o r r e c t i o n of C C 1 -induced fu iminant h e p a t i c f a i l u r e . Eiocharov A . . Sp i rov V.. Rochkova H . . Shnyra A . 1 ,aboratory of Molecular and Celluiar Card io logy Piational Cardiology Research Center Academy of Medical S c i e n c e s , Moscow, USSR

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26 MONOCYTE INTERLEUKIN 1 (IL1) AND TUMOR NECROSIS FACTOR (TNF) PRODUCTION INDUCED BY AQUEOUS EXTRACTS FROM HEMODIALYZERS

Mononuclear cells (PBMC) from patients treated by hemodialysis can show functional signs of activation. To elucidate the mechanism of this phenomenon aqueous extracts (AE) of cellulosic dialyzers (HD) were tested for their ability to induce in vitro generation of monokines in PBMC. HDs containing Cuprophan (CU) and Hemo- phan (HE) were studied. AE were prepared following an extreme modality of extraction by filtration of 0.5 liters of water from the dialysate to the blood compartment. AE were then dried by lyophiliza- tion and incubated with PBMC. IL1 and TNF were assayed by biologic or radioimmuno- logic methods. AE from steam-sterilized, dry-stored, or gamma-radiated CU and HE HDs resulted in cytokine activity not different from negative controls. By contrast, AE from ETO-sterilized, dry- stored, CU HDs caused significant IL1 and TNF production. This monokine inducing activity could not be neutralized by the addition of polymxin B and was heat unstable indicating that the cell activating stimulus was not endotoxin. Our results demonstrate that the AE induced activity found with some HDs can be el$- minated by the choice of the appropriate sterilization mode (steam-dry, or gamma- wet) or by a prerinse with saline. M.Blumenstein, H.W.L.Ziegler-Heitbrock*, H.Ackstaller, B.Schiller, H.J.Gurland, Nephrology Department and Institute for Immunology*, University of Munich, FRG.

28 KREPiSE N P N n - m PNWmY TITERS m m- N-T26 PERITCNPS i" n\FusIcN.

Tne mti-irdin antrbody titer was awssed in 47 ilrdir d e p - dent diabetic patients who hd undergone ccntinucCS peritoneal insulin infusicn for 58.9 2 3.2 mtk (rxge 6-84 mh). Two types of & were achhistered : aCjdic porcine inwk 40 U/ml and mtrd p c k insulin 100 U / d . CarparjsOn of the results of variolls p r m t e r s analyzed kfcre p q and after prrp trcabnmt showed rhe foUowlng : man b l d g l m , 194 5 8 q / d l WFLE 128 2 5 q / d l (p < 0.Cx)I) ; WAI 10.4 0.1 % (p < 0.001). HprglyCemic epjsods e w y month s @ m t l y decreased (48.8 2 6.5 % vefm 20.7 5 2.3 96 (p < 0.001) ; hrposlycenic episos were not & d y reduced (14.2 _t. 1.7 % versus 9.3 2 1.2 Yd. M y ilrdir requirerrnts were S@ufkantly rech.Ked (51.25 8 U/24 h verslls 42.2 4 U/24 h., p < 0.001). The mtiirwlin antifdy titers significantly increased : 2.79 2 0.6 % &jng the prepmp-perid - 6.9 2 1.5 % ( P < 0.001) m patients receive acidic i r d h and 10.6 2.1 % h patients eeated with rmtral i m h (p < 0.001). We d u d e that hgh levels of antiindin antibodies were axxiated with reckd jnsllin requirerrnts ard hTproved mtat~hc cmuol, 9ig@mg that, e m when kuk is ccrrplexed with it a n W y it is sti l l mtabolic reactive. chother pcssibility is that VKUlin antrbody rorplexes sthdate tk irdin rezeptm.

0.3 % - 8.3

Arrificial Organs, Vol. 13. No. 4, 1989

290 ABSTRACTS OF THE Vllth WORLD CONGRESS

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31

CONTRIBUTIONS OF ANIMAL MODELS TO THE INVESnGATION OF INFECTION AND THKOMBOSIS IN THE TOTAL ARTIFICIAL HEART The incidence of infection and thrombosis are the two most significant deterrents to the widespread clinical use of the total artificial heart (TAH). Investigation of these two pathological processes in a population of experimental animals receiving UTAH-100 hearts has been carried out and a comparison between this &la and clinical results wiU be presented. This comparison shows a similar incidence of infection in boch short and long term recipients, a similar specuum of organisms involved and similar periods of onset of infection. Evaluations of immunological function in our experimental animals has shown initial functional activation of neuuophils following cardiopulmonary bypass and device implantation followed by a prolonged period of reduced function as measured by random migration, chemotactic response and respiratory burst activity. Similar findings have also recently been reported from a group of human patients and may represent a significant factor in the onset of infection. The sites of thrombogenesis within devices have also proven to be similar in the experiment animals and the clinical recipients. The incidence of identifiable embolic sequelae varies between the two species due to differences in vascular anatomy and blood flow distribution. This review has indicated that calves are an appropriate model not only for TAH implantation but also for the investigation of pathological processes and possible treatment modalities.

@ePorv L. Burns and Don B. Olsen Artificial Heart Research Laboratory, University of Utah Salt Lake City, Utah, USA

ECHCCARDIOGRAPHY DURING LEFT W R I C U L A R ASSIST To investigate causes of reduced pump f l ow

rates during mechanical \ e f t ventr icu\ar assist we performed intra-operative epicardial echo- Doppler w i t h colour f low mapping (CFM) in 5 calves a t elective removal of an implantable mechanical device (LV apex/descending aorta). Counterpulsation during sinus rhythm caused m i l d LV shutdown. 3/51 devices had good f lows; CFM demonstrated blood f l ow into the apical conduit and out from the return conduit a t the aorto- conduit junction. Ventricular f ibr i l la t ion was induced t o test the effectiveness of circulatory support. Pump f low rates f e l l and r i gh t heart pressures rose i n a l l cases. I n 2 calves echo showed LV cavity shut-down; adjusting pump parameters resolved th is and improved f l ow rates. In 1 calf the r ight heart dilated rapidly wh i l s t the LV cavity remained normal. 2/5 devices had longstanding low f l ow rates due t o pannus formation. CFM showed l i t t l e f l ow into the apical conduit in both. We conclude that echo/Doppler during l e f t ventricular assist provides essential information about native heart function and causes of reduced pump f low rates.

Catherine Carey , T.R.Graham, D.Wrington, P.S.Withington, P.G.Mills, C.T.Lewis me London Hospital, London, U.K.

30

32

PLASMA EXCHANGE(PE) ANTIC0 AGULAT I ON PERFORMED BY PROSTAGLAND1 N I,( PG I,)PLUS HEPARIN(Hp) AND ACD SOLUTION Discontinous PE with PGI~(Sng/kg/rnin)toge ther with low dose Hp(5-6 IU/kg/min),trea tment A,and ACD solution alone,treatment B,is studied.PE is performed on a blood cell separator discontinous flow centri fuge.In vitro platelet aggregation(PA)by ADP 2.5 p M / n i l and activated partial thro mboplastin time (aPTT)are measured at start and 180' aafter in 8 patients.

Treatment A Treatment €3 1 Start 180' Start 180' PA 30+3 23+3 53210 5 0 2 1 2 aPTT 27?1 2 9 2 2 30+2 3224 Hp and ACD are anticoagulants commonly used in PE.The potential harmful effect of systemic HP with removal of large anlo unts of circulating coagulant factors,es pecially in blood patho1ogy.i~ known:in this situation low HP dose decreases ad verse Potential systemic affects and r i sk of concomitant thrombosis in extracor poreal circulation is avoided by simoul taneous PGI, infusion-Citrate metabolism is impaired in hepatic o r renal disease: the risk of citrate toxicity may be avoide d by treatment A.Decreased in vitro PA at end-treatment A suggests thrombocyte deact ivation by PGIZduring PE extracorporeal circu1ation.Thi.s preliminary study shows that treatment A may be a safe alterna tion anticoagulation. Marcellc! Camici,Lorenzo Evangelisti, Piervittorio Fosella.

University Hospitals,Pisa.rtaiy.

THE EFFECTS OF Ca++ AND 1,25(OH)2D3 ON PERIPHERAL BLOOD MONOCYTE (PBM) ACTIVATION IN HEMODIALYSIS (HD) PATIENTS.

It is known that PBM hyperactivation, leading to the release of abnormal quantities of cytokines, may play a primary role in the bioincompati- bility reactions (BIR). Moreover, it has been shown that cytoplasmic (Cy) Ca++ is important in the activation of immunocompetent cells and that 1,25(OH)2D3 has immunomodulating effects in viiro

We have therefore evaluated in 12 HD patients the effects in vitro of incubating PBM with 1,25 (OH)2D3 and/or Ca++ on the Cy Ca++ levels and on the production of Interleukin-1 (IL-l), Prosta- glandin E2 (PGE2) and Leukotriene B4 (LTB4).

Results: in the presence of Ca++ there was a dose-dependent increase in the production of I L - 1 and LTBA (cytokines having a helper function in the immune response) associated with an increase of Cy Ca++. At the same time, the production of PGE2 (cytokine with suppressor function) was reduced. The incubation of PBM with increasing doses of 1,25(OH)ZD3 and Ca++ togheter potentiated the aforementioned effects, while in the presence of only 1,25(OH)2D3 there was no modification of the various parameters.

These results stress the importance of Ca++ and 1,25(OH)2D3 in the activation mechanisms of PBM in HD and for devising prophylactic measures for BIR. Silvia Carazi *, Albert0 Canlraluppi**, Ihx W i t ** and Silvano Lapri **

logy Unit, St. P G ' s Hosp, Savona, ILdy *, We Rcund Lake, USA

Artijkial Organs, Vol. 13, No. 4, 1989


33 MULTIFACET APPROACH OF ARTIFICIAL LIVER SUPPORT: H E M O P E R F U S I O N , PROSTAGLANDIN E2, AND M I C R O E N - CAPSULATED HEPATOCYTES.

Coa ted c h a r c o a l hemoper fus ion improved the s u r v i v a l rates o f f u l m i n a n t h e p a t i c f a i l u r e i f u sed i n t h e e a r l i e r g r a d e s of coma (Chang e t a1 1 9 7 8 , Gimson e t a l , 1 9 8 2 ) . C e r e b r a l edema i s o n e o f t h e p r o b l e m s i n f u l m i n a n t h e p a t i c f a i l u r e . Development of c e r e b r a l edema c a n be p r e v e n t e d b y i n j e c t i o n o f p r o s t a g l a n d i n F2 i n s o l u t i o n ( D i x i t a n d C h a n g , 1 9 8 7 ) o r i n b i o d e - g r a d a h l e p o l y l a c t i c a n d m i c r o c a p s u l e s (Zhou & C h a n g , 1 9 8 8 ) . V i a b l e h e p a t o c y t e s w e r e m i c r o e n c a p s u l a t e d w i t h i n a r t i E i c i a 1 c e l l s t o form a b i o - a r t i f i c i a l l i v e r (Wong & Chang, 1986, 1 9 8 8 ) . T r y p a n b l u e s t a i n e x c l u s i o n t e s t i n g showed t h a t 60% of t h e e n c a p s u l a t e d h e p a t o c y t e s r ema ined v i a b l e i m m e d i a t e l y a f t e r e n c a p s u l a t i o n . E n c a p s u l a t e d r a t h e p a t o c y t e s w e r e x e n o g e n t c l y t r a n s p l a n t e d by i n t r a - p e r i t o n e a l i n j e c t i o n i n t o n o r m a l m i c e a n d g a l a c t o s a m i n e i n d u c e d l i v e r f a i l u r e mice. The p e r c e n t a g e v i a b i l i t y of the h e p a t o c y t e s i n s i d e f r e e f l o a t i n g m i c r o c a p s u l e s i n c r e a s e d f rom 62% t o n e a r l y 100% af te r 29 d a y s o f i m p l a n t a t i o n i n m i c e . I n a g g r e g a t e d m i c r o c a p s u l e s , t h e r e were no v i a b l e h e p a t o c y t e s . I n mice i m p l a n t e d w i t h f r e e ra t h e p a t o c y t e s , no v i a b l e h e p a t o c y t e s w e r e o b s e r v e d 4 a n d 5 d a y s a f t e r i m p l a n t a t i o n .

TYS Chang, O i r e c t o r and P r o f e s s o r A r t i f i c i a l C e l l s and Organs Resea rch C e n t r e M c C i l l U n i v e r s i t y , M o n t r e a l , PQ, Canada, H3G-lY6

___ . _ _ __

35 EVOLUTIONARY AUTOMATION IN EXTRACORPOREAL CIRCULATION

Extracorporeal circulation (ECC) enables replacement of the patient's cardiac and pulmonary functions during open heart surgery, by an artificial heart-lung system. Automation of the control of certain parameters of this system is possible, and several applications have been developed in our laboratory: level regulator, automatic clamp, automatic suction. These independently regulated modules can also be commanded by a PC microcomputer type monitoring system. The level regulator permits to command the pump speed accordingly to the blood level variation in the reservoir of the oxygenator, during surgical ECC. When coupled with the automatic clamp, the regulator permits to obtain soft starting and stopping of ECC over variable periodes of time from 30 secondes to 5 minutes.

A high performance modular system is thus available, providing a decision aid and the possibility of complex interactions between the regulated parameters. Other modules could be added in future as bubble detection, regulation of oxgygen air mixture to optimize tissue oxygenation during ECC.

CHAUVEAU N., VAN MEURS W. L., BARTHELEMY H., MORUCCI J.P. INSERM U305. H6tel DIEU, TOULOUSE FRANCE

34 COMPARISON OF ALBUMIN RECOVERY IN CASCADE FILTRATION FOR HUMAN AND BOVINE PLASMA

For the purpose of optimizing cascade filtration in therapeutic plasmapheresis, the albumin sieving coefficient (SC) and transmembrane pressure (Pun) were measured using cellulose acetate hollow fiber filters (PF 100, AKZO), with fresh bovine or human plasmas, in dead-end mode, at various inlet plasma fluxes (1.2 cm/min<Qi/Sc4.8 cm/min).

It is found that P m rises exponentially with time, the rate of increase being proportional u) the inlet plasma flux Qi/S. Moreover, it appears that albumin SC is independent of Qi/S and is governed mainly by Ptm. Numerical values can be interpolated in this way:

Ptm=Poexp(at) with a=A(Qi/S)" SC=Soexp(-pPtm).

Po=5.6 mmHg A=0.0403 n=1.86 S04.96 p=5.89 (mmHg)-l

Po=24 mmHg A=0.0014 n=1.47 SeO.94 p=1.087 (mmHg)-l

For human plasma, we have found:

and for bovin plasma :

For Qi/S=3.6 cm/min, Ptm rises to 500 mmHg in about 26 min for human plasma, and 36 min for bovine plasma. Simultaneously, SC decreases from 0.8 to 0.45 as h reaches 500 mmHg for human plasma and from 0.75 to 0.4 for bovine one.

Total protein concentration is larger in the case of human plasma, C=57 g/l against C=39 g/l for bovine plasma, diluted by collection on CPD. This fact may explain the faster plugging observed with human plasma. However due u) the smaller value of p, the decrease of SC with time is about the same for bovine and human plasma.

C.Charcosset, L.H.Ding. M.Y.Jaffrin, U.Baurmeister*, UTC, Compikgne, *AKZO, Wuppeml

36 Zffects of pulsatile flow(Pz) and sortic counterpulsation (ACP) on mymudial reperfusion injury(MR1)

'To evaluate the efficacy of P?' an3 Act' in nini- mizing MRI, 23 sheep, divided into 2 uroups were reperfused by conventional nonpulsatile flow(xoup 1) , or by PF and ACP(grouD 2) for 120 tminu-ces after 30 minute global myocardial ischenia. .?en of 13 sheep(77%) in group 1 developed venLricu1c.r fibrillation(VF) and could not wean fro-- C-' , whereas this happened to only 4 of 10 ( ~ W ) in group 2 (P< U.01) . ~WO~,was decrease . ir, . ro ip 1 bu t remained at the preischemic level i3 'roo? 2. The peroxidation products and CX i?. coron3q sinis blood were increased without si:-xifican-i differences between two groups. i;:lectrmicroscocic examination revealed nuclear chrmatin clu-pinu ax? riarqination, mitcchrondril we1 linu and franmen- tation of cristae etc in C~OUD 1, hovi,ever, tiere were less ultrastructural abnornali-cies in .z'rou? 2. SoCiiurn content in Wch subendocardiup, mi^ su:- epicardium in group I was significantly ;!iz.ler than that in group 2, beins 9.98+1.lU a m 7.jZc 0.36 versus 7.1120.60 and 5.77+0.G9~q/z c . q i.rt(?c 0.05) respectively. Water accumulatien occurre:' in kt!j qroups but mcre prominent in prolip 1, 54.30+0.33 versus 82.58fP.47%(P< 0.91). lhis study shows that PF and ACP after qlobal myocardial ischemia causes less injury Over that with nonpulsatile reperfusion in regard to lower incidence of \:, hiqher W02, less ultrastructural damages and less sodium and water accumllaLion in subendocardirim. It is remnahle apply Pr and ACP during open heart Surgery. 3. y. Chianq, c. H. Ye, Y. J. GU, X. D. ';ao, c. R. Wildevuur, a d Y. S. ipept. of Cardiothoracic surcery, -'.enji Yos~ital Shanghai 2nd :led Jniv. Shari:hai, >China



37

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UTILITY OF TRANSVERSE:FRONTAL PLANE QRS VOLTAGE RA- fiO(T/F)IN LONG TERM CARDIOLOGIC EVALUATION OF IRC PA-TIENTS ON EXTRACORPORFAL BLOOD PURIFICATION

QRS voltage in transverse and frontal planes cha qes in a concordant fashion.Factors wich increase voltage in precordial leads,such as concentric left ventricular hypertrophy,usually augment ORS poten- tials in limb 1eads.Dilated cardiomiopathy with ECF ritention and other several factors might exert an increase on QRS in the transvers? plane and a decre ase in the frontal plane.T/F ratio variations along 5 years in 43 IRC pts on extracorporeal blood purification were evaluated.T/F compared with ecocardio- graphy (Left ventricular end diastolic diameter LV- ED) every six months.T/F unchanges in 20 pts,decreases in 9 pts and increases in 14 pts.There are no differences between these groups in age and in dialytic age.No difference might be given to different types of blood purification,since there is a similar distribution in the Rroups (60% HD,20% HDF,20% HF).Pts with a decreased T/F had a diminished LVED with a significant correction of cardiac hypertrophy.When T/F increases there is an increase in LVED with a dilatative component that could be given to underlying desease (mixed cryoglobulinemia,policy- stic kidnev desease.severe hypertension).T/F could correlate with fluctuations in hemodynamic status and could be a sign i n long term longitudinal cardiologic evaluation in IRC pts on blood purification. Cinimienti S.,Perrone F.,Mele G.,Cristofano C. Nephrology Department U.SL. TA/7 - Yanduria (TA) ITALY

PRETRANSPLANT IMMUNOADSORPTION PLASMA TREAT-

REPORT An increasing problem in uremic patients is HLA-immunization which

can make renal transplantation impossible. Successful pretransplant plasmapheresis in highly immunized patients has been reported but in some patients no effects were seen. Plasma treatment with immunoadsorption (IA) can selectively remove circulating antibodies. This therapy modality was used in 5 highly immunized patients waiting for renal transplantation. 3 1 plasma separated from the patients with filter (Asahi Plasmatlo OPT-5L) was run through an irnrnunoadsorpLion column (Asahi lmmusorba IM-TR) three times a week during four weeks (in loml 12 UeatmentS per patient). Immunosuppression was started after the first IA with cyclophosphamide (50-100 mg) and prednisolone (starting dose 60 mg daily tapering to 15 mg after 4 weeks) continuing until transplantation.

Results. Until now 3 pdents completed I A Ueatment. Successful renal uansplantations were performed in 2 patients. One patient only recently completed IA and the remaining 2 patients still are on IA treatment.

Biochemical evaluation of serum (possible from the first ueawi patient R.A.):

MENT OF HLA-IMMUNIZED PATIENTS - PRELIMINARY

38

40

Cytotoxicanlibodia I& IgM IgA Fibrinogen against 24 panel cells (g/l) (dl) (gh) (g4)

Before IA 22/24 10.4 3.91 1.59 4.35 Afier IA no 12 On4 1.4 0.14 0.43 0.59

Conclusion: These preliminary results indicate that IA may be an efficient treatment for elimination of HLA-antibodies.

Bo G Danielson, Bjom Wikstrtim. Ulla Backman. Bengt Fellsutim. Gunnar Tufvesonl, Olof Sjbkrg2 Dept of Internal Medicine, ITransplantation, 2Clinical Immunology, University Hospilal, Uppsala. Sweden

AUTOMATIC CONTROL OF TOTAL ARTIFICIAL HEART TO SIMULATE THE KEMODYNAMlCS UNDER NATURAL HEART CIRCULATION

We developed control system of total artificial heart (TAH) during exercise simulating the circulatory response of natural heart. The following procedures were taken to develop this system. 1) Measurement of hemodynamics and physical

activity rate (PAR) of natural heart goats during treadmill exercise.

2) Estimation of cardiac output from PAR using a non-linear model.

3) Development of a pneumatic artificial heart (AH) driver with high speed controllability and a control unit to deliver CO calculated from PAR beat by beat.

4) Evaluation of the physiological condition of the TAH goat during exercise controlled by this system. Using this control method, CO of TAH goats was

similar to that of natural heart goats during treadmill exercise. Hypertension was observed during exercise. This hypertension was considered to be derived from two causes. One was high inflow and outflow resistance of cannulae between AH pump and living body. The other was the disorder of peripheral circulatory control mechanism in TAH animal, such as increased sympathetic activity, insufficient secretion of atrial natriuretic polypeptide (ANP) and decreased sensitivity of peripheral circulatory system with ANP. T .Chinze i , K.Maeda, K.Imachi, Y.Abe, K.Imanishi, K.Mabuchi. T.Yonezawa. LFujimasa, K.Atsumi Reseach Center for Advanced Science and Technology, The University of Tokyo. Tokyo, Japan

RANDOMIZED DOUBLE-BLIND TRIAL OF L-LACTATE, BICARBONATE, AND ACETATE FOR HIGH-EFFICIENCY DIALYSIS. We performed high-efficiency dialysis (Qb - 5x

body weight, Baxter CA210 dialyzers, for 9 weeks on 8 chronic hemodialysis patients; each patient was randomized to 3 weeks on each of 3 dialysates: 39 mM acetate, 35 mM HC03 + 4 mM acetate, or 42 mM L-lactate + 4 mM acetate. delivered using a 2-container system. and correction of acidosis were monitored. Prior to breaking the blind, each dialysis treatment was assessed to be a success or failure depending on whether or not substantial symptoms (headache, dizziness, nausea) occurred. Dialysis time (mean 3.0 A 0.3 hours) was set to achieve a Kt/V of 1.1 based on urea kinetic modeling. The percentage of failed dialysis treatments

with acetate (45% ? 11 SEM) was significantly higher than with L-lactate (11% f 3.7) or with bicarbonate (13% 4.3) [ A vs L, p - 0.040; A vs B, p - 0.037; B vs L, p NS]. The predialysis HCO3 values at the end of each treatment period, an indication of overall correction of acidosis, were similar after A (20.2 5 0.7 mM), L (21.2 0 . 4 5 ) , B (21.8 5 0 . 5 8 ) , p NS. There were no overall blood pressure differences between A , L, o r B. The results suggest that L-lactate, provided at

a total base concentration of 46 mM, can maintain correction of acidosis in a high efficiency setting, and is comparable to bicarbonate with regard to freedom from adverse symptomatology.

S . Dalal, R. Gupta, D. Gupta, M. Ajam, F.J. Manahan, T.S. Ing, and J.T. Daugirdas. Hines -Loyola Medical Center, Hines, IL, USA 60141.

All dialysates were Symptoms



41

43

COMPARATIVE STUDY OF MICROENCAPSULATED RAT ISLETS IMPLANTED IN DIFFFERENT DIABETIC MODELS IN MICE

Microencapsulation of islets of Langerhans has been proposed to permit non syngeneic islet transplantation for the treatment of human diabetes mellitus. Microencapsulated rat islets of Langerhans (alginate-pdylysine microcapsules) were transplanted into the peritoneal cavity of diabetic mice (400 rat islets per mouse) in order 1) to evaluate the ability of this xenograft correcting hyperglycemia in different models of diabetes and 2) to examine the implanted material recovered from the recipients after several weeks. 1) In the low-dose streptozotocin model in C57BL/6J mice (n = 17): plasma glucose level decreased in 9 mice, from 24.4 L 1.5 to 10 & 1.7 mmol/l, and remained below 13.9 mmol/l up to 60 days. In 8 mice, only a transient effect was observed. Empty capsule transplantation had no effect. 2) In the highdose streptozotocin model in Balb/c mice (n=14), 6 had a sustained (over one month) decrease in plasma glucose concentration from 22.3 2 0.4 to 9.5 & 0.4 mmol/l, with no effect in the other. In these two models, plasma insulin, in successfully transplanted mice, was higher in fed than in fasted state. 3) Microencapsulated rat islets had no effect on plasma glucose in male NOD mice made diabetic by cyclophospharnide treatment (n= 10). Thus, microencapsulated rat islets can improve the diabetic state in some, but not all diabetic mice, are inefficient in the NOD model. However it was impossible to recover from the peritoneal cavity of these three groups of mice microcapsules containing intact islets, and microcapsules were consistently surrounded by an inflammatory reaction, which remains a major concern.

S Darquy, D. Chicheportiche, F. Capron, C. Boitard, J. Rouchette. G. Reach Service de Diabetologie et dAnatomopathologie. H6tel-Dieu, and Service d'lmmunologie Clinique, INSERM U25. H6pital Necker, Paris, France

Heparin Conjugated PHEHA Microspheres for Albumin Separation

In this study, heparin conj l~gated P H E W microspheres were

developed for albumin separation f rom blood p!asrn3. H;drophilic

po1;iHEMh) particles. in diameter 300-500 p., were prepared by

suspension copolvmerization technique carr ied out in an aqueous

medium The presence o f carhoryl groups in the structure and desired

h:.drophobicil'f were supplied b{ adding comnnorners. methzlcrylic

a ' i d (nMk1 arld mrthy ln- Ie t tocry la t~ IIIMA) into the monomer

mixture. respectivelv. The particles were activated bv CMr-method

a t alkaline pH and neutralized by NaHCO: solution. Af ter the

acli.3!ion s k p . the binding o f hepzrin molecule5 to the ac t ive sites on

1I.e SurfaLe of pdrliclrs 'NBW psrforn-led in t iwar in soluliori arid the

amount 01 binded heparin to Lhs carr ier was determined spectro-

phottnmetrirally Albumin adsnrption-ei?ltion studies were performed

in a bioaffinit; column, 1.6 cm in d ime te r , an0 3.5 cm in height

Altdimin cori ier~trat ions in !he liquid phase *rere fallohad by ga rma

srntillation technique o i rzdio-!abelled (Technetium ii9 m ) part icles.

The prel iminary resu!ts of this study showed the applicability o f

these novel bioiorbent: for the separalion of albumin.

A D E i l l i L i M KIREIIITCI. E PISKIN Hxet tepe University. Chemical Engineering Dept , Ankara. Turkey

42 EVALUATION OF A NEW INOTROPIC AGENT IN CHRONICTAH ANIMALS.

Chronic TAH i m p l a n t a t i o n permi ts a s e p a r a t e e v a l u a t i o n of c a r d i a c and p e r i p h e r a l e f f e c t s of drugs . T h i s model w a s used t o e v a l u a t e a new ino- t r o p i c a g e n t , enoximone (E), p r e v i o u s l y shown t o a l l o w e f f i c i e n t pharmacologica l b r i d g e t o u r g e n t c a r d i a c t r a n s p l a n t a t i o n . 5 H o l s t e i n c a l v e s (9Okg BW) were implanted w i t h a J a r v i k 7-70. Cont inuous moni tor ing of AoP, CVP, PAP and LAP was done. C a r d i a c o u t p u t was main ta ined a t a c o n s t a n t l e v e l ( f u l l - f i l l , f u l l - e j e c t mode, fixed r a t e ) th rou- ghout t h e exper iments performed on a q u i e t , s t a b l e , awake c a l f . E . w a s i n f u s e d as a 10 min. I V b o l u s and d a t a recorded o v e r 8 h o u r s . A dose of 1 , 2 and 3 mg/kg BW w a s t e s t e d on each c a l f . Data showed a peak e f f e c t a t 30 min. w i t h a 16 % 2 5 drop i n sys temic v a s c u l a r r e s i s t a n c e s (SVR) and no s i g n i - f i c a n t change (drop of 4 % k 2 ) i n pulmonary vas- c u l a r r e s i s t a n c e s (PVR) f o r a 2 mg/kg E. b o l u s . No dose r e l a t e d p e r i p h e r a l e f f e c t could be poin ted o u t (same d a t a f o r 1 mg and 3 mg/kg). These effects were compared t o t h e v a s o d i l a t a t i o n observed w i t h a 100 nglkgjmin . I V i n f u s i o n of PG 12, which l e d t o a 20 % 2 drop i n SVR and 50 % 2 9 drop i n PVR .

Conclusion : 1. E . has a marked sys temic vasodi - l a t i n g e f f e c t . 2 . C l i n i c a l d a t a on drop i n PVR a r e more r e l a t e d t o i n o t r o p i c p r o p e r t y of E . t h a n t o an h y p o t h e t i c a l pulmonary v a s o d i l a t i n g e f f e c t . 3 . Optimal dose of E. a p p e a r s t o be 1 t o 2 mg/kg BW

FH. Deleuze, J . Okude, F. Wan, M . Binhas, S. Brunet , D.Y. Loisance . Cent re Recherches Chirurgicales ,CHU H . Mondor 8 , r u e du G&n&ral S a r r a i l , 94000 C r e t e i l , France

4 BOVINE ENDOTHELIAL CORNEAL CELLS AS EXTRA- CELLULAR MATRIX FOR HUMAN ENDOTHELIAL CELL SEEDING.

To optimalize patency of small caliber vascular prosthesis endothelialisation of their inner wall has been proposed. Bovine endothelial corneal cells (BEC) are known to express collagen IV and laminin on their membrans. Both of them are not thrombogenic.Class1 and Class11 antigens of the Major Histocompatibility Complex are not detectable at all on these cells.They are easy LO handle and may be used for infected patiena. Our technic to prepare exlm cellular matrix(ECM) from BEC consist to sature cells with bFGF after a confluent layer is obtained.Hypotonic choc destroy immunogenic components but preserve biochemical structure of ECM and its ability LO present bFGF. Human endothelial cells (HEC) were purified from omental tissu obtained during surgery. Then it is minced, washed, and digested in a mixed solution of collagenase-dispase and then passed under rneshs. Cells are selected on a Percoll gradient, plated on Primaria plastic dish for 3/4 days, until confluence. They are tested with factor VIII and W 6 - 3 2 antibodies, using indirect imrnunofluorescence. After these controls cells are seeded.on glass cover slip precoated by poly-L-Lysine, Laminin, Fibronectin and extra cellular matrix of BEC.First results showed a doubling time of 30 hours on BEC versus 54 hours on the other coatings.After confluence HEC present a shape change on BEC ECM closely comparable to in vivo morphology. Quality of this neoendothelialisation is evaluated by Factor VlII and proslacyclin secretion.Cell -cell interactions are evaluated by SEM and TEM.These results indicate 1)heterologous ECM is a suitable substrate for growing human endothelial cells 2)The ability of ECM to lrap bFGF provide an active presentation of this growth factor on biomaterials.

Despranges Po-,Martin-Mondiere C"*,Tardieu M-, Loisance D",Banitault D- O Centre de Recherches Chirurgicales, CHU CRETEIL FRANCE * Service dHtmatologie CHU Piti&Salp&m&re. PARIS FRANCE - Lab. de Biotechnologie .UniversitC Paris XII, FRANCE

Artificial Organs. Vol. 13, No. 4, 1989


45 CLINICAL EVALUATION OF CAPIOX E, A NEY HOLLOY F I B E R OXYGENAIOR, OURIN6 HODERATELY PROLONGED ECC.

V . Di Vlncmzo, 6. Boico, 6. Sclploni, N. kclal, 1. Cappillrtti, 6. Santarrlll, 6. Liberl, A.M. Calaflori Drpt. of h e i t h e s i r and Cardiac Surgrry, Unlvrriitl di Chiiti, Italy.

Capior E i r L nrw hollow fiber oxygenator Into rhlch blood flows outrldo and q a i I n i l d t th, ilcroporoui capillariri. It can b i connictod rlth thm ECC clrcult uplldi tht arttrial pump and rllori the urn of prniuri drprndint dwlcti. Furty-rlght pItItnti, OpCrrtid tor rlictlvi iyocardlal rrvaitul arf zati on, htvr bran studied. Thr hllorlnp cllnlcal and laboratory paratiterr havp boen roipired betrnm two hoioqnnoui q r w p i ditlnrd b y thi UIC of Caplox E ( C E I ITtrumo) and Dptiflor (0 I11 ISorin BloridlcI),

C . E . l n . 24) 0.11 (11.24) p ECC t i t o 9O.If13.0 98.3f17,O (0.05 B a i l E~crir,I5' -1.2f2.2 -0. MI. B ni Bast Excrit,md ECC -1. btl,? -I .2t i t 6 n i Plrtelrt l o l l (21 5s. 3fl1. I 2hhfE.6 (0.0025 Protrln l o i i 1x1 35.117,B 32. 7f b , l n i f r c i plain^ Hb II.Sf8.O 22.5f12.9 n i G ~ i l b l o o d votuii I 10' O.UfO.11 0,39iO. 1 nr Grnlblood volurtI3S~C 0.3fO.12 O.4BfO.06 CO.01 Heat ~ r c h m p r r tfflclonry SO.9f10,1 S E . 6 f l Z . b (0.02s

Chrst tubi dra!nrpa(1l/r/l2 h) 217.616P.O 219.3183.2 nr Thr Capiox E hollow f i b w orypmator, riployod for ioderatily prolonqtd ECC, p l v i i brttrr r i tu l t i than thr Opt l f lo I1 II far ar platelet l o t i and oxy9rnation art concernid. YI conrldrr Caplox E a flrit c h o l i i orygrnator for i t s ronvtnImL prlcelprrfortinrr ratlo.

(Prqi and lhoiai)

47 A RESEARCH PROJECT ON P m m r DATA WITORING WRING CIRCKATORY ASSISTANCE .

Patients' physico-chemical data collection and evaluation is an essential part ot the correct nanageaent ot ventricular assistance application. bany experimental and clinical studies suggest the use at various procedures in order to obtain the most accurate hemodynamic and respiratory monitorization, as well as blood constituents concentration and function control. Nonetheless trom the current literature it is not sutficiently clear what is really necessary to provide the best care for the patient and, in the meantine, to optinize the procedure's budget.

The present research project was developed aiming at the tollowing goals:

- to plan the complete range ot technological, anaesthesiological, intensive care, nursing , laboratory and diagnostic commitment in order to carry out a "state ot the art" clinical application o f VADs - t o reduce the learning tiae and to sake a neu procedure efficiently

operative from the beginning - to actively involve a multidisciplinary consultant corittee - to stimulate instrument designers, producers and dealers to take

advance f r m the knorhow expressed by an extreme clinical challenge. Hardware and software tacilities were prepared in order to make

clinical measurements available and easily processed. Some of these were taken with redundant devices in order to use one result as like as the control ot the other. The multipararetric output was transmitted , via a wire connection, to an adjacent room separated tron the patient's clean unit by a crystal wall and thus real tine data evaluation, recordings and clinical discussion were accomplished away from the unit. The entire system was operative during the successful 31 day long

WADS applitation as a bridge to transplantation pcrtormed at Niguarda Hospital in 1988, under the supervision o f the IRCV group ISion, Svitzerlandl and supported by C I and ICMYIOS Project (CMt and FIAT S.p.A.1.

V. Di Vincenzo, 8. Ilarit, b. Ferranter, C. Cattanis Cattedra di Rnestesiologia e Rianilazione Universita' di Chieti *Ill Servirio di Rnestesia e Rianiaazione, Osp.Niguarda,bilano, ITkY

46 THE HETbEOLlC A!D CLINICAL EFFECTS OF A CONTINUOUSLY ROTATING ARTERIAL PUNP (RHONE POULENCI, WHICH DELIVERS PULSATILE FLOW. Rhine Poulenc (RPI IS a non occlusive, contrnuously rotating, three rollers pump with an elliptically shaped section of the p a p head tube. These aspects g i v e the pump flow a pulsatile character. In our Departient the RF arterial p u l p has been employed for rore than 300 elective cardiac operations in aduls. The following clinical and laboratory paraieters have been conpared between two hoiogeneous groups of 100 patients, defined by the use of different pumps: RP and a traditional continuous flow roller punp (TAANSOlE6R - T O ) .

W i n = 1001 TO [n= 100) P ECC time 79.5t17. b 77.3!18.5 ns base E., 15' -0.422. I -1.4t2.4 (0.0025 base E.,end ECC -0.5tl.8 -1.1t1.9 !0.0125 free plasia Hb 19.3t12.8 IE.l t10.0 ns platelet loss 24.9!11.6 31. Oil 1.7 (0.0005 protein loss (1) 34 .Bib .8 34.5t7.0 ns rewaining efficiency 30.8!13.2 54.7t9.b (0.01

lPape and Thonasl 1 P R I during rewarning 10.122.6 13. 3fI . E (0.0005 Pulsatile flow delivered by RP arterial pulp seem to nbtiin a bstter tissue perfusion, as evidenced b y the lower level of TPRI and of BE debit and by the shorter rewariing tine conpared with the ones obtained with TO.

V. Di Vincenzo, 6. h c o , N. Acciai, L. Cappelletti, 6. Scipioni, F. Zecchini, #A.M. Calafiore. Departrent of Anesthesiology and ICardiac Surgery, Faculty of Medicine, The University of Chieti, Chieti, Italy.

48 CORRECTION OF SECONDARY I~hD'lUNOUbYICIhN- CY AS A RESULT OF HEMAPHERESIS

To s tudy the p o s s i b i l i t i e s of probab- l e r educ t ion of pos tope ra t ive pyo-septi- c a l complicat ions (PPSCs) i n p a t i e n t s ( p t s ) operated with a p p l i c a t i o n of ex t r a - co rporea l c i r c u l a t i o n (EC) we used plasm- a p h e r e s i s (PA) i n p reope ra t ive per iod ( 1 2 p t s ) , hemosorption (HS) dur ing EC ( 3 0 p t s ) and p u r i f i c a t i o n of donor 's blood (DB) s t o r e d f o r more than 3 days (11 p t s ) . During PA procedure we removed not more than 500 mL of plasma. We s t u d i e d t h e in f luence of PA upon pa- t i e n t ' s immunoreaction according t o the fo l lowing t e s t s : T-, B-lymphocytes, "medium molecular" l e v e l ("UIVL) pofy: morphonuclear l eukocy tes (PMlTs) a c t i v i - t y , i n t o x i c a t i o n l e u k o c y t i c i ndex ( I L I ) , l e u k o c y t i c d - g l y c o p r o t e i n (LHG), K+; we i n v e s t i g a t e d L i G i n plasma of DB befo- r e and a f t e r HS. We d id not observe PPSCs i n t e s t e d group of p t s , w h i l e i n c o n t r o l group we had 18%.

2 - 3 procedures of PA doubled PMNs, improved T-ce l l f u n c t i o n s and enhauced B-cell r e a c t i v i t y i n p t s w i t h s imulta- neous i n c r e a s e of phagocyt ic index. HS of DB reduced 2.5 t imes concen t r a t ion of K S and 1.5 t imes concen t r a t ion of M G .

Thus, t he above-mentioned regimes of PA have average immunostimulating e f f e c t Dmitr iev A . A . , Shalnev B.I., Abdiev O . S . , Suskova V.S. I n s t . of Transpl. and A r t i f i c . Organs, Moscow, USSR

Artificial Organs, Voi. 13, NO. 4, 1989


49

51

DEVELOPMENT OF COMPUTER AIDED MOTION ANALYSIS (CnmA) SYSTEM FOR IMPLANTED TILTING DISK VALVE

A semi-automatic data acquisition and processing system was developed to assess functions of the implanted tilting disk valve quantitatively. A new system consists of a computer controlled cinefilm loading device, a CCD camera, a frame memory, a 16 bits personal computer, a superimposer and CRT displays. The cinefilms were loaded and then superimposed on the CRT display by the CCD camera. Since most of the valve position was complete open or shut in the implanted tilting disk valve, data acquisition of the valve contour on the CRT screen was carried out by mouse cricks at the first frame of each mode to minimize processing time. Adjusting the position shift of the valve seat due to heart beat, data acquisition was carried out semi-automatically from the second frame to the last frame(common1y 30 to 40 frames) just prior t o the next mode.

analyze about 90 frames of the cinefilm compared t o that by a manual procedure. With the Medtronic Hall valve implanted in a patient without any clinical symposium, 63 to 66 degrees of open angle was calculated by this system. The CAMA system with the semi-automatic data acquisition system can quantitate functions of the implanted heart valve easily. In addition it is promissing for further shortening of analysis time with newly developed valve image analysis program.

T.Dohi. T.Horiuchi, Y.Ohta, H.Matsumoto The Univ. of Tokyo, Tokyo, Japan

20 min of data analysis time was shorted to

MECHANICAL CIRCULATORY ASSIST BY ROLLER PUMP SYSTEM USING HYDROPHILIC HEPARINIZED POLYMER COATED TUBE For mechanical circulatory assist we invented an

integrated circuit system (from inflow cannula to outflow cannula) which was consisted of hydrophilic heparinized polymer coated tube (AnthronR). This system was driven by a roller pump. After experimental studies, this system was clinically applied to 10 patients for profound heart failure after cardiac surgery from April 1987 to the end of 1986. The underlying disease was ischemic heart disease in 4, valvular disease in 5 and congenital anomaly in 1. Left heart bypass was employed in 6 patients combined left and right heart bypass in 1 patient and veno-arterial bypass without oxygenation in 3 patients. simultaneously in all patients. After withdrawal of cardiopulmonary bypass, heparin was neutralized with protamine to keep the hemorrhage minimal in the operative field. ranged from 21 hours to 6 days and the assisting flow volume ranged from 0.8 to 5.0 l/min(mean 2.2 L/min). thrombo-embolism. Six patients were successfully weaned from this support system and 5 were discharged from hospital.

requires only a simple circuit with conventional roller pump. 2) It can be rapidly instituted without systemic heparinization. Therefore, we believe that this system is very effective for patients who cannot be weaned from cardiopulmonary bypass after open-heart surgery. Shoji Eguchi, A.Saito.J.Hayashi,H.Ozeki,N.Noguchi*. Y.Futami*. The 2nd Depart. of Surg. Niigata Univ., Niigata. Toray Medical Industryc. Tokyo, Japan

Intraaortic balloon pumping was done

Duration of this support

None of the patients showed signs of

Our system has 2 major advantages: 1) It

31 f e c t of lieiuocar3o$erfusion on IL-E and IL-2-iyntiiesizing ahmli-

~y of l eukocy tes iu p a t i k t s w i t h termi- r ia l renal i n s u f f i c i e n c y ( T R I )

We z tud ied 33 T R I p a t i e n t s p r i o r and 48h a f t e r H zeance as t o t h e e b i l i t y of Liononuclear ce l l s o f p e r i p h e r z l b lood t o produce IL-1 and IL-2. 'We eloo i n v e s t i - %lied FGA-induced p r o l i f e r a t i o n of lym- Siocy te s , a c t i v i t y of I a - c e l l a a g a i n s t 51-Cr l a b e l e d K-562, a c t i v i t y of poly- rnorphonuclear 1 eukocyt e s and rnoAno cyt e s in a NST-t e s t , and t h e l e v e l of c i r cu - l a t i n g in-nune complexes a n d concentra- t i o n of I g G , Ll and A.

Following 48h a f t e r Ii , w e observed no s i g n i f i c a n t chdnges in f u n c t i o n a l a c t i - v i t y o f polyniorphonuclear leulcocyt e s ,30- nocytea, and ITK-cells, but considerably i n h i b i t e d p r o l i f e r a t i v e response t o PGA o f B e r i p h e r d blood Lilononuclear c e l l 3.

I n h i b i t i o n of ini t igen-podaced p r o l i - f e r a t i o n i s appa ren t ly a s s o c i a t e d with changes 5 n EL-2 r e c e p t o r s expres s ion r a t h e r t?in with IL-2 proauc t ion , since :ve revealed no s i d f i c a n t changes i n the spontaneous and FGA-induced 15-2 product€oton, but cons ide rab le r e d u c t i o n of p r o l i f e r a t i v e response t o exogenous recombinant IL-2,

P o s s i b l e rneclmnismo of t h e r evea led e f f e c t s a r e dlscuzsed.

G . Z . i ) r a m i i K , Y e .Ya .3aranI LoYa.Kusl&o ,I~,A.E:alinina, I. I.Czvinchuk, IoA.D%hS .'J,Deinyanova Inst .Urology ,Kiev

EPARIN-INUID CXTRnniRPOaPL LCL PECIPITATICN (HIP) I N Tt€ 5 E f Y N M Y P M I C N IT comxJ9RY t fART DISA% (a0) ASSOCIATED WITH TYA I1 HYFEKXLES-IA

Regular LDL-apheresis is an effective tool f o r lowering LDL-cholesterol (LDL-C) levels. We now have over 3 yr experience with the HELP-LDL-apheresis system in which more than 1100 aphereses have been performed on 22 patients with type I 1 hypercholesterolemia. Pre-apheresis LDL-C levels !.were reduced by 27% and post-apheresis levels by 72% as compared to pre-treatment levels. A further reduction in LDL-C was obtained by sjmultaneous therapy with HMG-CoA reductase inhibitors. Treatment compliance has been excellent. Clinical jmprove- ments in 10 patients with angjographically documented CHD after 1 year regular treatment sere as follours: 9/10 amelioration o f angina pecto- ris: 7/10 improvement in exercise dyspnoe; 7 /10 increased ecg capacity. These findings were associated w j th favourable changes in rheological parameters (plasma viscosity, erythrocyte aggregation) and muscle oxygen tension due to the coprecipitation o f fibrinoqen and LDL-C. Control coronary angiographies are now being perFormed after 2 yr regular treatment. InitIal data indicate no progression of CHD in this period, and in some cases a regression.

Artificioi Organs. Vol. 13, No. 4, 1989


53 SWELLING BEEAVIOR OF DEHYDBATED-CROSSLINKRD GELATIN GELS

5% glutaraldehyde crosslinked gels have shown excellent blood compatibility as coatings for cardiac prostheses. A method was developed for producing thin dehydrated coatings using a proprietary dehydration procedure and EO sterilization. The swollen surfaces of rehydrated versus wet (original) gels were compared.

Within 30 min of saline rehydration, dry 30-50 films on textured surfaces became smooth and

uniform and comparable to original gelatin gels. Mechanical test results after rehydration showed values for strain remain unchanged (39.3210.0 to 40.027.8%), but stress increased (2.79t1.21 to 4.22 t 1.60 dynes/cm2, ~(0.01). The contact angle data reported XC values of 26.1 and 30.4 dynes/cm for original and rehydrated gels. Using a coulometric titrimeter, the measured water content of original gels was reduced from 85% to 3.49: and 73.29: for dry and saline rehydrated gels. Gels shrunk 88% of their original length after rehydration, however, the thickness of all pump coatings remained stable.

Two hour incubations with bovine platelet rich plasma showed no differences in platelet reactiv- ity or morphology when compared to original gels. Light microscopy and SEM showed no evidence of gel cracking or surface defects after pump endurance testing for 5 weeks.

The process of dehydration eliminates the wet storage and sterility problem of such hydrogels and provides a stable film coating for a variety of blood contacting substrates. Hideto Emoto, Helen Kambic, Hiroaki Harasaki, Yukihiko Nos*, Cleveland Clinic Foundation, Cleveland, Ohio, USA

55 SKIN TEST SENSITIVITY IN ZINC-DEFICIEKT PATIENTS ON -0- AND PERITONEAL DIALYSIS

Cellular imnune function in uremia might be the result of Zinc deficiency. Menifeatations of acquired defects in cellular immunity were studied by akin test sensitivity.

Fourty-one stable patients on regular dialysis treatment (34 on Hemdialysis and 7 on CAPD) were chosen for the study.

Skin tests were performed using a multiple-antigen test (Multitest Merieux. Lyon, France) . Intra-deml injection was made on forearm and results were noted 10 min and 48 h after the injection of 7 different antigens (Tetanus, Oiphteria, Streptococcus, Tuberculin, Candida, Trichophyton and Proteus). An area of papule of at least 2-mn diameter at the injection site after 48 hr represents a positive test. Results are expressed as number of positive test. Skin tent performed in the same conditions with Glycerol as control medium was always negative. Blood samples were drawn from patients at the same moment of skin test procedure for plasma Zinc concentration deterdnation by atomic absorption apectrophotometry.

Mean (f SEMI planma Zinc concentration was 13.3 f 0.5 w l / L which is statistically different (p < 0.001) from the reference normal value (16.8 f 1.5 pmol/L). Mean plasma Zinc concentration from CAPD patients (12.3 f 0 . 9 ) is not significantly different from that of HD patients (13.6 f 0.6). The number of positive response (M f SEM) for all patients was low (2 .3 f 0.2 vs 7.0) and suppressed positive skin test indicated a defect in cellular immunity.

Since Zinc deficiency accounts in part for the demise of immunity, Zinc supplementation could be of great interest for the patients on regular dialysis treatment.

G. Fournhr, M. Corvazier, N.K. Man A.I.R.B.P., Chartres and Necker Hospital, Paris, France.

54 A TRIAL TO INFLUENCE COMPLEMENT ACTIVATION USING NO CALCIUM AND MAGNESIUM IN DIALYSATE Ca and Mg ions participate in activation of complement system and different blood cells. To decrease such activation in hemodialysis we investigated changes in the complement factor C3a, the electrophoretic mobility (EPM) of lymphocyte subpopulations as an indicator of cell activation as well as WBC and platelets using dialysate without Ca and Mg during the first 15 min of hemodialysis and Cuprophan(R) containing dialyzers. Standard Ca and Mg concentrations were subsequently established in dialysate. Results: In comparison to standard hemodialysis using Cuprophan(R) containing dialyzers we could not find any differences in C3a, the EPM of peripheral lymphocytes as well as WBC during hemodialysis without Ca and Mg in dialysate during the first 15 min. However we found an until now not described significant lower platelet count after 30 and 75 min. A possible explanation for these findings could be the relatively low clearance of ionized Ca and Mg (50 ml/min) despite Ca and Mg free dialysate which resulted in a decrease of 30 X of predia- lyzer ionized Ca and Mg concentration. In conclusion we can state that no significant change of complement activation or WBC including lymphocyte subpopulations could be detected but a delayed platelet reaction occured using no Ca and Mg in dialysate in the initial phase of dialysis.

H.Klinkmann; Dept. of Internal Medicine, W.Pieck University Rostock, GDR

D.Falkenhagen, G.S.Brown, U.Thomanek,

56 EXTENDED SUPPORT P R I O R TO CARDIAC TRANSPLANT USING A LEFT VENTRICULAR ASSIST D E V I C E WITH TEXTURED

An abdomina l l y p o s i t i o n e d p u l s a t i l e l e f t v e n t r i c u l a r a s s i s t dev i ce (LVAD) w i t h unique t e x t u r e d b l o o d - c o n t a c t i n g su r faces was used as a b r i d g e t o c a r d i a c t r a n s p l a n t i n 9 p a t i e n t s a t ou r i n s t i t u t i o n . The f l e x i n g diaphragm o f t h e LVAD i s f a b r i c a t e d o f i n t e g r a l l y t e x t u r e d po lyu re thane , and t h e t i t a n i u m pump housing i s t e x t u r e d w i t h s i n t e r e d t i t a n i u m microspheres. Four p a t i e n t s r e q u i r e d extended suppor t (>30 days) , r a n g i n g f rom 35-110 days, w i t h pump f l ows o f 4-7 L/min i n f i x e d - r a t e mode. Two p a t i e n t s a re w e l l a t 6 and 12 months a f t e r h e a r t t r a n s p l a n t (HT); 1 d i e d o f l i v e r f a i l u r e 49 days a f t e r HT; and 1 HT candidate, who has been on t h e dev i ce >110 days, i s do ing ve ry w e l l . D u r i n g extended LVAD suppor t , adequate a n t i t h r o m b o g e n i c i t y was achieved w i t h d ipy r idamo le (75 mg, 3/day) and a s p i r i n (80 mg/day), r e s u l t i n g i n normal p ro th romb in and p a r t i a l t h r o m b o p l a s t i n t imes i n t h e s e p a t i e n t s . There was no ev idence o f thrombogenic ep isodes. I n each p a t i e n t , plasma- f r e e hemoglobin l e v e l s remained acceptable th roughou t suppor t , and b lood chemis t r y and hemato log i c va lues r e t u r n e d t o normal . A t h i n , pseudoneoint imal l i n i n g , f i r m l y a t t a c h e d t o t h e b l o o d - c o n t a c t i n g sur faces, was observed a f t e r LVAD removal. Based on our r e s u l t s , t h i s LVAD, w i t h t e x t u r e d b l o o d - c o n t a c t i n g su r faces t h a t a l l o w min imal a n t i t h r o m b o t i c agents w i t h o u t increased r i s k o f thromboembolic comp l i ca t i ons , i s an e f f e c t i v e b r i d g e t o t r a n s p l a n t , even when pro longed suppor t i s needed. O.H. F r a z i e r , Takeshi Nakatani , Michael McGee, Steven Parn i s , K u r t Dasse,* J. Michael Duncan, V i c t o r P o i r i e r . * Texas Hear t I n s t i t u t e , Houston, TX and *Thermo Cardiosystems, Inc. , Woburn, MA, USA

BLOOD-CONTACTING SURFACES

Artificial Organs, Vol. 13. No. 4, 1989


57 A X .ALTERNATIVELY DRIVEN SKELETAL bIUSCLE VEVTRICULE (St.") CARDIAC ASSIST DEVICE

?]any s t u d i e s on c a r d i a c a s s i s t d e v i c e s us ing on SFlV r e q u i r e p r e c o n d i t i o n i n g f o r 6-9 weeks a s a countermeasure t o p r e v e n t s k e l e t a l muscle f a t i g u e . T h e r e f o r e t h i s method d o e s n o t seem t o he i n d i c a - t e d i n c a s e s o f a c u t e c a r d i a c f a i l u r e . However,we performed exper iments t o deve lop a l t e r n a t i v e l y d r i v e n S W s u s i n g t h e l a t i s i m u s d o r s i and major p e c t o r i s muscles a s a c a r d i a c assist d e v i c e wi th- ou t p r e c o n d i t i o n i n g .

4 d u l t mongrel dogs were used . In o r d e r t o eva- l u a t e t h e adequacy of t h e a l t e r n a t i v e l y d r i v i n g p a t t e r n o f t h e SMV, two fundamental exper iments were c a r r i e d o u t . The f u n c t i o n of Sblvs prepared by r o l l e d peduncula ted s a r t i u s muscle was s t u d i e d hydrodynamical ly i n two gr0ups;cont inuous d r i v i n g f o r 1 hour : i n t e r m i t t e n t d r i v i n g ( d r i v e : r e s t = l : l ) f o r 3 h o u r s . The f u n c t i o n of S:.lVs prepared by non - r o l l e d l a t i s i m u s d o r s i and major p e c t o r i s mus- c l e s (polyure thane s a c s were p laced benea th t h e s e muscles) was s t u d i e d . I n t h i s exper iment , S!,IVs were d r i v e n f o r 30 minutes i n t e r m i t t e n t l y . A l l SIWs were s t i m u l a t e d by e l e c t r i c a l b u r s t s .

I n t e r p r e t i n g t h e r e s u l t s o f fundamental s t u d i e s , it was recognized t h a t r e p e t i t i o n o f 30 minutes d r i v e and r e s t is t h e best a l t e r n a t i n g d r i v i n g p a t t e r n f o r SkNs. On t h e l a s t s tudy , t h e f u n c t i o n o f S W s was n o t reduced. Therefore , t h e r e s u l t s o f t h i s s t u d y i n d i c a t e t h a t a l t e r n a t i v e l y d r i v e n twin SI.IVs can be used a s c a r d i a c a s s i s t d e v i c e s wi thout r e q u i r i n g p r e c o n d i t i o n i n g .

Tadashi Fu j ikawa,Hiroyuki Suesada,Kazuhi to Osada, Te tsuzo Mirayama, Shin Ishimaru. Kin- ich i Furukawa, Department o f Surgery,Tokyo Medical C o l l e g e , Tokyo, Japan

59 C L I N I C A L EVALUATION OF A NEW HEMOPHAN MEMBRANE

A new hemophan membrane i n which t h e percent - age of c e l l u l o s i c OH-groups s u b s t i t u t i o n by t e r - t i a r y amino compounds i s s l i g h t l y decreased as compared t o s t a n d a r d hemophan membrane was t e s t e d f o r t h e c l i n i c a l performance i n 6 hemodialyzed p a t i e n t s w i t h c h r o n i c r e n a l f a i l u r e and compared t o b o t h s t a n d a r d hemophan and cuprophan membrane.

Using t h e s a m e hol low f i b e r modules (Kawasumi Lab.1nc.) by t h e t h r e e membranes, t h e i n c r e a s e of C3a l e v e l s and t h e d e c r e a s e of l e u c o c y t e counts a f t e r 15 minutes of hemodia lys i s were most remarkable i n cuprophan membrane and t h e same de- g r e e s i n two o t h e r membranes. The changes ofb-TG l e v e l s and p l a t e l e t c o u n t s w e r e smal l i n a l l t h e t h r e e membranes. Using 500 I U b o l u s i n j e c t i o n and 500 IU/h c o n t i n u o u s i n f u s i o n of h e p a r i n , t h e pro- l o n g a t i o n of a c t i v a t e d c o a g u l a t i o n t i m e w a s lesser, and r e s i d u a l blood volume w i t h i n t h e module f i b e r s a f t e r e a c h d i a l y s i s s e s s i o n was l a r g e r i n s t a n d a r d hemophan membrane t h a n i n two o t h e r membranes.

I n c o n c l u s i o n , t h e new hemophan membrane i s keeping a good q u a l i t y of s t a n d a r d hemophan membrane and shows a b e t t e r an t i - thrombogenic i ty than s t a n d a r d hemophan membrane.

-_ Yoshikazu F u j i t a , Tadayasu Shono, Oshi Inagaki H i d e t a r o Mori, S e i s h i Inoue D i a l y s i s U n i t , Hyogo Col lege of Medicine Nishinomiya, Japan

58 COMPARATIVE STUDY I N REMOVING OF G U A N I D I N O COM- POUNDS FROM THE PLASMA AND RBC BY HEMODIALYSIS AND PROTEIN PERMEABLE HEMODIAFILTRATION

In t h i s s t u d y , Guanidino Compounds(GC) i n t h e plasma and RBC wi th 24 normal s u b j e c t s , 24 c h r o n i c r e n a l fa i lure(CRF) p a t i e n t s and 32 hemodialysis(HD) p a t i e n t s were measured by HPLC. and t h e re- m o v a b i l i t y of GC from plasma and RBC were compared between two t y p e s o f hemopurification methods; i e : hemodialysis(HD) and p r o t e i n permeable hemo- d i a f i l t r a t i o n ( P P H D F ) .

The plasma GSA v a l u e w a s 393.22 1 5 7 . 5 ~ g / d l i n t h e CRF group, and 4 9 6 . 6 2 3 2 7 . l ~ g / d l i n t h e HD group. RBC GSA was approximate ly 1/5 t o 1 / 1 0 t h e plasma c o n c e n t r a t i o n i n both t h e CRF and HD groups.

I n t h e normal group methylguanidine(MG) was d e t e c t e d only i n t h e u r i n e . Plasma MG i n the CRF group was 1 0 . 4 t 5 . 9 p g / d l a g a i n s t a s i g n i f i - c a n t l y h i g h e r 37.62 1 8 . l p g / d l i n t h e HD group. RBC MG i n t h e s e two groups was 1 .5- to 1 .9-fold t h e plsma l e v e l , t h e MG t e n d i n g t o accumulate i n t h e RBC.

The GC mean removal r a t e s by HD were a s f o l l o w s : plasma creat inine(CRN1, 67.1% RBC CRN, 65.3%; plasma GSA, 84.4%; RBC GSA, 46.4%; plasma M G , 49.6%; RBC M G , 30.9%. Thus, t h e GSA and MG removal r a c e s were low f o r RBC. The RBC MG con- c e n t r a t i o n fo l lowing HD w a s a mean v a l u e of 45.5 u g / d l , which corresponded t o t o x i c level from i n v i v o exper iments . Thus E/G removal by HD was con- s i d e r e d i n s u f f i c i e n t . PPHDF showed f a r b e t t e r removal of plasma and RBC MG t h a n HD.

T . F u j i s h i r o , H.Yamashita, M.Hasegawa, T.Tsuzuki , H.Hasegawa, M.Mizuno, T.Ogawa, and S.Kawashima D e p t . of I n t e r n a l Medicine, F u j i t a g a k u e n H e a l t h Univ. , Toyoake Japan

60 ANTITUMOR EFFECTS OF A NEW INTERLEUKIN 2 SLOW DELIVERY SYSTEM ON MURINE METASTATIC LIVER CAN- CER

A s a form o f immunotherapy f o r a d v a n c e d c a n c e r , t h e i n v ivo a d m i n i s t r a t i o n of i n t e r - l e u k i n 2 ( I L - 2 ) is b e i n g u s e d c u r r e n t l y i n c l i n i c a l t r i a l s . However, t h e h a l f - l i f e of IL-2 i s ext remely s h o r t . I n o r d e r t o main ta in IL-2 c o n c e n t r a t i o n l o n g e r , w e have developed a new IL-2 slow d e l i v e r y sys tem, IL-2 m i n i - p e l l e t , and e v a l u a t e d i t s a n t i t u m o r e f f e c t s on m u r i n e h e p a t i c metastases. IL-2 m i n i - p e l l e t , whose c a r - r i e r m a t e r i a l is a b i o d e g r a d a b l e c o l l a g e n d e r i v e d from bovine s k i n , is rod-shaped wi th a l e n g t h of 10 mm and a d iameter of 1 mm and can r e l e a s e 1x106 u n i t s of SL-2 s lowly f o r 72 h r . The a d m i n i s t r a t i o n of IL-2 m i n i - p e l l e t i n t o t h e s p l e e n of m i c e on d a y s 7 and 1 0 a f t e r t h e i n t r a p o r t a l i n j e c t i o n of c o l o n - 2 6 rnurine adenocarcinoma was e f f e c t i v e i n reducing t h e number of m e t a s t a t i c n o d u l e s on day 21 (10.3*4.6; p<O.O5), compared t o u n t r e a t e d con- t r o l s (90 .8f23 .1) . To de termine t h e mechanism of t h e s e e f f e c t s , s p l e n o c y t e s of treated mice were t e s t e d f o r c y t o t o x i c a c t i v i t y i n 51Cr r e l e a s e assay. On day 2 a f t e r t h e a d m i n i s t r a t i o n , l y t i c a c t i v i t y a g a i n s t YAC-1 [ n a t u r a l k i l l e r (NK) sen- s i t i v e t a r g e t ] , EL-4 ,[NK r e s i s t a n t t a r g e t ] , and colon-26 c e l l s was augmented. These r e s u l t s sug- g e s t t h a t t h e l o c a l a d m i n i s t r a t i o n of IL-2 mini- p e l l e t i n t o t h e h e p a t i c c i r c u l a t i o n can induce lymphokine a c t i v a t e d k i l l e r (LAK) cells i n vivo and be a p p l i e d t o t h e immunotherapy of metas- t a t i c l i v e r cancer . Toshiyoshi Fuj iwara , Kenichi Sakagami, J u n j i Matsuoka, S h i g e h i r o S h i o z a k i , Susumu Uchida, Kunzo Or i ta : F i r s t D e p a r t m e n t o f S u r g e r y , Okayama U n i v e r s i t y Medical School , Japan


298 ABSTRACTS OF THE VIIrh WORLD CONGRESS

61

63

THE EFFECTS OF DRIVING MODES OF VENTRICULAR ASSIST DEVICE ON CFLSDIAC PERFORMANCE IN W I N E HEARTS -SYNCHRONOUS SYSTOLIC DRIVING OR DIASTOLIC DRMNG? - To determine the superiority of the two

driving mcdes ( i.e., EcG synchronous systolic driving mode (SD) and ECG synchronous bastolic driving mode (DD)) of left ventricular assist device, left ventricular assistance (drained from the left atrium and infused to the ascending aorta) was established using an air- driven, diaphragm-typ pump in seven anesthetized dogs. We measured assist flow, left ventricular stroke work, left and right coronary arterial flows and DPTI/TTI in both SD and DD. Assist flow was significantly higher in SD than in DD (SD: 10202189 rd/min vs D3: 860~300 ml/min, ~ ~ 0 . 0 5 ) and stroke work was significantly lower in SD than in DD (SD: 3.6~3.4 g m - m vs DD: 5.653.4 p . m , p<O.O1 ) . Coronary arterial flow and DPTI/TTI were similar in b t h drivinq d e s (LCX; SD: 17.3210.5 rnl/min vs DD: 17.7210.2 ml/min, N S ) (RCA; SD: 9.623.7 ml/min vs DD: 9.354.4 ml/min, NS) (DPTI/TTI; SD: 1.69~0.67 vs tD: 1.6820.42, NS). These data suggest that SD decreased left ventricular stroke work by increasing assist flow. SD had no disadvantages in regard to coronary flow and DFTI/TTI. We concluded that SD was superior to DD in terms of left ventricular unloading.

Kiyotaka F'ukamachi, Toshihide Asou, Ituniaki Kishizaki, Yuichirou Nakamura, Kouichi lbkunaga Division of Cardiovascular Surgery, Kyushu University, Faculty of Medicine, r'ukuch, zapan

ULTRPSOXIC MOTOR DRIVEN ARTIFICIAL HEART

i s d r i v e n by a n u l t r a s o n i c motor.

where t h e r o t a t i n g f o r c e i s o b t a i n e d by a mechanical v i b r a t i o n of p i e z o e l e c t r i c ceramics . The r a t e d speed , t o r q u e , and o u t p u t power of t h e u l t r a s o n i c motor used i n t h i s s t u d y a r e 100 rpm, 3.8 kgf-cm, and 4 W , r e s p e c t i v e l y .

Two k inds of t h e a r t i f i c i a l h e a r t d r i v e r s are made, one equipped w i t h a c r a n k c h a i n t o c o n v e r t r o t a t i o n of t h e motor i n t o r e c i p r o c a t i o n of t h e p u s h e r s , t h e o t h e r w i t h a p l a t e cam. The p e r c e n t a g e s y s t o l e of t h e c rank c h a i n t y p e d r i v e r i s f i x e d a t 50%, w h i l e t h a t of t h e p l a t e cam o n e i s 40%. The two s a c s , blood chambers, a r e 51 mL ( l e f t ) and 44 mL ( r i g h t ) in volume and a r e made of po lyure thane rubber . BjGrk-Shiley monos t ru t v a l v e s are p laced a t t h e inflow and o u t f l o w of t h e s a c s . The main body of t h e d r i v e r i s made of aluminum a l l o y and carbon s t e e l . The mass of e a c h a r t i f i c i a l h e a r t i s approximately 800 g .

of 57 t o 95 beats /min w i t h a f l o w r a t e of 2 . 3 t o 4.1 Llrnin on a mock c i r c u l a t o r y system.

A c r a n k c h a i n type a r t i f i c i a l h e a r t i s connec ted to a 18 kg dog and i t i s observed t h a t t h e to rque of t h e u l t r a s o n i c motor i s not enough f o r t h i s a r t i f i c i a l h e a r t . T h e r e f o r e t h e second motor i s added t o t h e a r t i f i c i a l h e a r t and experiment i s a g a i n c a r r i e d o u t u s i n g a 25 kg dog. The problems as w e l l a s t h e p o s s i b i l i t y of t h e u l t r a s o n i c motor d r i v e n a r t i f i c i a l h e a r t are c l a r i f i e d .

S . Fukunaga, Y. Hamanaka. H. I s h i h a r a , T . Sueda, S . Hayashi and Y . Matsuura. F i r s t Dept . Surg. & R e s . I n s t . of Replacement Med., Hiroshima Univ. Sch. Med., Hiroshima 734, Japan .

An a r t i f i c i a l h e a r t is made and t e s t e d , which

U l t r a s o n i c motors a r e based on a new p r i n c i p l e

The a r t i f i c i a l h e a r t works a t t h e d r i v i n g r a t e

~ _ _

62 AN EXPEXIMENTAL STUDY ON THE EFFECTIVENESS OF TYIE DIXECT DIAP%?AGM PACING

diaphragm pacing, canine experiments were carried out. The diaphragm was stimulated u s i n g monopolar intramuscular electrodes implanted bilaterally in the diaphragm muscle at a distance 1 cm apart from the insertion of the phrenic nerve into the diaphragm. The electrodes for temporary cardiac pacing were used.

I n an anesthetized adult mongrel dog weighing 14 kg , the evoked tidal volume was measured at different current levels of three current Xveveforns: a biphasic anodal current, a biphasic cathodal current, and a biphasic alternating bidirectional current. Using a biphasic cathodal waveform, the evoked tidal volu~e cculd easily be control led by the current amp1 itude.

I n another anesthetized mongrel dog weighing 11.5 kg , for 36 hr the diaphragm pacing was done continuously. A biphasic cathodal waveform was used. Ir~ulse duration, impulse burst frequency and respiratory rate were 0.15 msec, 23 Hz and 15/nin, respectively. The current am91 itude was set at a level causing about 00 sj of maximal evolted tidal volume. The current amplitude of the impulse train during a burst was ramped by a gradual increase to breathe smoothly. Over a 36 hr ?eriod there was no change in evoked tidal volume. ';iithout fatigue the effective ventilation was achieved. The direct diaphragm pacing is a promising method for full-time ventilatory

To evaluate the effectiveness of the direct

SUDOOrt . . . Y.Fu ku i *, M.K i mu r a*, M.Togawa*, T.Sug i ura**, Y.Zarada*** *Grad. Sch. of Electr. Sci. &Tech., **Xes. Inst. of Electr., Shizuoka Univ. ***lst Dept. of Surg. !<anainatsu Univ. Sch. of bled., Hamamatsu, Japan

64 NON-INVASIVE BLOOD GLUCOSE WASUREMENT SYSTEM AS A GLUCOSE MONITORING DEVICE IN ARTIFICIAL ENDOCRINE PANCREAS

As an altenative way of long-term glycemic monitoring, the non-invasive blood glucose measurement system has been developed. By analyzing the infra-red absorbance with attenuated total reflection (ATR) prism, glucose had a characteristic absorbance at peaks with the wave numbers near 1033 and 1080 cm-l. And measured signals were proportional to lucose concentrations.

Blood corpscles, cRolestero1, albumin and other . metabolites interfered the absorbance spectrum of glucose and shifted the base-line upward significantly. To eliminate these interferences and then measure glucose concentrations quantitatively in serum and blood samples, the feasibility of the calibration curve of fasting sample as an individual charac-teristic was studied. From these experiments, it is concluded that by using infra- red absorption spectroscopy, blood and serum glucose concentrations could be measured quantitatively or monitored if the base-line drift and interference were subtracted.

The characteristic absorbance specific to glucose molecule was also observed in the spectra through mucous membrane as lip and skin as finger tip. To measure glucose concentrations quantitatively from the spectra through skin and mucous menbrane, the computer mediated separation algorithm is under development.

Although the development of sophisticated measurement system will be a key technology, this method might be quite useful for monitoring system of glucose in diabetics in near future.

H. Fukushima, K. kajiwara & M. Shichiri Department of Metabolic Medicine, Kumamoto University Medical School, Kumamoto 860, Japan



65 POTENTIATION BY HEPARIN OF SHEAR-INDUCED PLATELET AGGREGATION

Thromboembolism i s one of the ser ious complica- t i ons in heparin therapy. However, the exact mechanism of t h i s complication i s not known. Although i t has been shown t h a t heparin poten t ia tes a g o n i s t - induced p l a t e l e t aggregation, t he so l e e f f e c t of heparin on p l a t e l e t functions has not been well charac te r ized because of t he technical problems. We have recent ly developed the mechanical device f o r continuous measurement of p l a t e l e t aggregation induced by varying shear s t r e s s i n the absence of any aggregation inducer ( M.Fukuyama e t a l , Thromb. Res. 1989 ) In t h i s paper, the e f f e c t s of heparin and heparinoids on shear-induced p l a t e l e t aggrega- t i on (SIPA) were inves t iga ted . P l a t e l e t r ich plasma ( P K P ) i n the presence of heparin was applied i n t o cone and p l a t e viscometer adapted f o r continuous recording of l i g h t transmission. Unfractionated heparin (Novo, Denmark) enhanced SIPA a t shear s t ces s of 18 dynelcmz in a dose dependent fashion over t h r range of 0.1-1 .O u/rnl. Low molecular wei- g h t heparin (Kabi, Sweden), on the o ther h a n d , showed much l e s s e f f e c t on SIPA. Heparinoids in- ClJding chondroitin s u l f a t e A , B , C and heparan su l - f a t e were a l so t e s t ed showing no s i g n i f i c a n t e f f e c t on S I P A . PKP from pa t i en t s congeni ta l ly de f i c i en t in fibrinogen o r p l a t e l e t membrane glycoprotein I I b I I I I a exhib i ted n o SIPA even in the presence of heparin. Our findings t h a t unfractionated heparin, not low molecular heparin, g rea t ly poten t ia tes SIPA in a low shear f i e l d , nay be important i n heparin therapy . M.Fukuyama, K.Kawakami, K.Sakai, I . I t a g a k i * , K.Kawano**, M.Handa** and Y.Ikeda**. Dept.Chem. Eng. Waseda Univ., Toray I n d u s t r i e s I r c . * and School of Med. Keio Univ.**

67 2. EPIDEP2IIDIS BIOFILMS: RIFAMPIN SYNERGY AND ANTAGON IS! ’ .

Medical d e v i c e - a s s o c i a t e d i n f e c t i o n may r e s i s t therapy due t o b a c t e r i a i n t h e b i o f i l m - s u r f a c e phase. B i o f i l m s p r e p a r e d from S. e p i d e r m i d i s , s e n s i t i v e i n t h e f l u i d phase , were r e s i s t a n t to a n t i b i o t i c s e x c e p t f o r r i f a m p i n . Rifampin a c t i v i t y was incomplete wi th t h e development of r e s i s t a n c e . W e examined a n t i b i o t i c s f o r p o s s i b l e synergy wi th r i f a m p i n . S tandard ized S . e p i d e r m i d i s b i o f i l m s were exposed t o a range of a n t i b i o t i c s each i n combinat ion w i t h r i f a m p i n , v a r y i n g c o n c e n t r a t i o n and exposure t i m e . Synergy w a s observed wi th some a g e n t s ( t e i c o p l a n i n , vancomycin) b u t r e q u i r e d l o n g exposure . Unpredic tab ly antagonism was demonst ra ted w i t h o t h e r a g e n t s (c l indamycin , g e n t a m i c i n ) . These f i n d i n g s emphasize d i s c r e p a n c i e s between f l u i d and b i o f i l m phase a n t i b i o t i c t e s t i n g and t h e need f o r f u r t h e r s t u d i e s t o p r e d i c t t h e r a p e u t i c outcome.

Raymonde Gagnon, John P r e n t i s , Gregory O b s t , Geoffry Richards . l ’ c n t r e a l General H o s p i t a l , McGill U n i v e r s i t y . Mont rea l , Canada.

66 DEVELOPMENT OF A COMPACT EXTRA-CORPOREAL MENBElANE OXYGENATIOPJ(ECM0) SYSTEM

I n r e c e n t y e a r s , ECMO i s used f o r t r e a t m e n t o f neonates w i t h r e s i p i r a t o r y f a i l u r e . We developed a p r o t o t y p e o f a compact ECMO system f o r t h e n e o n a t e s . The system h a s t h e f o l l o w i n g s p e c i f i c a t i o n s :

l ) A s i n g l e lumen c a t h e t e r i s used f o r bo th blood wi thdrawal and i n k s i o n .

2)The b lood i s d r i v e n by a diaphragm pump which i s c o n s t r u c t e d i n the same hous ing as t h e membrane oxygenator u n i t . The diaphragm p m p i s c o n t r o l l e d by a microcomputer based d r i v e u n i t which i s s e p a r a t e d from t h e oxygenator u n i t .

3 ) A c t i v a t e d c o a g u l a t i o n t i m e i s r e g u l a t e d by i n f u s i o n of a n t i c o a g u l a n t o r u l t r a - s h o r t a c t i n g a n t i c o a g u l a n t (nafamosta t m e s i l a t e ) .

4 ) I n o r d e r t o p l a c e on a b e d s i d e , t h e oxygenator u n i t i s des igned compact i n s i z e (L12 X W14 X HBcm) w i t h a low pr iming volume ( g o d ) , which a l l o w s ECMO w i t h o u t a d d i t i o n a l blood t r a n s f u s i o n .

ECMO exper iments w i t h i n t e r m i t t e n t V-V bypass were conducted on 3 mongrel dogs. The bypass b lood f low r a t e was 15(ml/min/kg) . I n t h e s e exper iments , t h e g a s exchange wi th t h e developed ECMO system w a s e f f i c i e n t enough to e l i m i n a t e t h e r e s i p i r a t o r y f a i l u r e induced by mechanical v e n t i l a t i o n . T h e system w a s cons idered a p p l i c a b l e t o r e s i p i r a t o r y a i d f o r neonates .

Akio FUNAKU€!Q,Ichiro SAKUMA, Yasuhiro FUKUI and Tsuyoshi KAWAMURA* Fac .of S c i . and Eng.,Tokyo Denki Univ. ,Sai tama

* Hyogo B r a i n and Hear t C e n t e r a t Himej i , Japan

68 4THEROSCLERDSIS I N A MOUSE MODEL O F CHRONIC “ENAL TAILURE.

A l e a d i n g cause of m o r b i d i t y and m o r t a l i t y i n p a t i e n t s w i t h c h r o n i c r e n a l f a i l u r e undergoing hemodia lys i s i s i schemic hear t d i s e a s e r e s u l t i n g from a c c e l e r a t e d a t h e r o s c l e r o s i s . I n o r d e r t o i n c r e a s e o u r unders tanding of t h e p a t h o l o g i c a l mechanisms under ly ing t h i s p r o c e s s , w e s t u d i e d mice of tvo i n b r e d s t r a i n s which a r e known t o be E e n e t i c a l l y s u s c e p t i b l e ( C 5 7 B L / b J ) and r e s i s t a n t ( A / J ) t o d i e t - i n d u c e d a t h e r o s c l e r o s i s .

by s e q u e n t i a l e l e c t r o c o a g u l a t i o n of t h e r i g h t r e n a l c o r t e x and l e f t nephrectomy, d u r i n g which t i m e t h e an imals were f e d normal r o d e n t chow, t h e a o r t a s of C57BL/6J, b u t n o t A / J , mice were found t o c o n t a i n a t h e r o s c l e r o t i c l e s i o n s , c h a r a c t e r i z e d by the presence o f macrophage-derived foam c e l l s . Serum c h o l e s t e r o l l e v e l s were s i g n i f i c a n t l y i n c r e a s e d i n mice o f b o t h s t r a i n s and t h e r e was a s t r o n g c o r r e l a t i o n between serum c h o l e s t e r o l and BUN l e v e l s . However, whereas serum t r i g l y c e r i d e l e v e l s were a l s o i n c r e a s e d i n uremic C57BLI6J mice, they were decreased i n uremic A/J mice. T h i s corresponded to h i g h e r serum p o s t - h e p a r i n l i p o p r o t e i n l i p a s e and h e p a t i c t r i g l y c e r i d e l i p a s e a c t i v i t i e s i n A / J than i n C57BL/bJ mice.

de te rminant of s u s c e p t i b i l i t y and r e s i s t a n c e t o t h e development of a t h e r o s c l e r o s i s i n c h r o n i c r e n a l f a i l u r e i n i n b r e d s t r a i n s of mice which may be expressed a t t h e l e v e l of l i p a s e enzymes.

R.F. Gagnon, J.L. S t e w a r t - P h i l l i p s and J . Lough, Montrea l Genera l H o s p i t a l Research I n s t i t u t e , Mont rea l , Canada.

S i x weeks a f t e r t h e i n d u c t i o n of r e n a l f a i l u r e

These r e s u l t s i n d i c a t e t h a t t h e r e is a g e n e t i c

Artificial Organs, Vol. I S , No. 4, 1989


PRESENCE OF A N ASCORBIC ACID METABOLITE IN THE 70 MICROTUBULE FORMATION INHIBITING FRACTION FROM UREMIC PLASMA.

formation plays an essent ia l ro l e in c e l l u l a r l i f e e.g. cytoskeleton, mi to t ic sp indle , axonal transport . Previously we demonstrated the presence i n uremic plasma of a chromatographic f r ac t ion (2-5-3) which i s a potent i nh ib i to r of in v i t r o tubulin polymerization with possible e f f e c t on axonal growth and the onset of uremic neuropathy.

In the present study we attempt t o fu r the r separa te and iden t i fy the ac t ive molecule i n 2-5-3- f r ac t ion using so l id phase ex t rac t ion ( ion iza t ion control w i t h buffered mobile phase on c18 reverse phase packing), UV, l H a n d 13C nuclear magnetic resonance and aminogram. The r e s u l t s show the main component of 2-5-3 f r ac t ion t o be ascorbic acid su l f a t e ( A A S ) . The o ther component i s l i k e l y of pept id ic nature ( P N ) . The inh ib i to ry e f f e c t on i n v i t r o tubul in polymeri- za t ion res ides e n t i r e l y i n PN.The experiment was repeated on urine from normal subjec ts with the same outcome. If t h i s in v i t ro e f f e c t occurs a l so in vivo i t would be possible t o believe t h a t PN might play a regulatory ro l e on in vivo mi c ro t u bul e format i o n .

The question remains whether the presence of AAS i n the same chromatographic f r ac t ion i s due t o mere coelution o r points t o a possible binding between AAS a n d PN. I n t h i s case one may hypothesize t h a t AAS i s implicated in PN metabolism. Gal l ice P . , Braguer D., Monti J .P . , Elsen R . , Durand G. ,Berland Y., Crevat A . Facul t ies of Pharmacy and Medicine, Marseil le, France

Tubulin polymerization leading t o microtubule

ENDOTHELIAL CELL APPLICATION INTO 72 TUBULAR PROSTHESES USING A STANDARDIZED ROTATION TECHNIQUE

Enothelial cell (EC) seeding in artificial vascular prostheses could include the antithrombogenic abilities of viable cells in the performance of prostheses. A rotational method was developed for seeding a homogeneous monolayer of endothelial cells into tubular vascular grafts, a specially constructed cell application device was developed for this purpose. In this study, parameters influencing the kinetics of cellular adhesion during rotational cell seeding in a seeding device for tubular prostheses were investigated: rotation speed, graft diameter, cell suspension level, inoculated cell number.

An optimal adhesion rate range of 4-10 rph was found, the adhesion rate was inversely proportional to the prosthesis diameter with the smaller prosthesis performing better than larger ones. A low cell suspension level increased initial adhesion rates up to reaching a complete monolayer within the inner surface of grafts. The optimal cell density is twofold higher than the confluation density of cells in culture flasks. The inoculated cell density did not affect the initial adhesion rate.

The study shows, that seeding endothelial cells in tubular vascular grafts in a homogeneous monolayer is possible prior to implantation by using the cell seeding device with the elaborated parameters of the cell seeding method presented.

3. Gerlach, H.H. Schauwecker . K.-M. Kreusel Chirurgische Klinik, Universitatsklinikum RUDOLF VIRCHOW/ Charlottenburg, Freie Universitat Berlin, West Germany

A N E W C O N C E P T F O R A T O T A L L Y I M P L A N T A B L E ARTIFICIAL H E A R T

A new t o t a l l y implantable a r t i f i c i a l hear t ( T I A H ) t h a t i s l i g h t e r , smal le r , simpler and more adaptable t o human spec i f i ca t ions has been designed. This new design includes the following concepts: (1) the t o t a l weight of t he TIAH i s l e s s than 400 gm which i s s imi la r t o the human hear t in weight; ( 2 ) the ven t r i c l e s a re operated synchronously with a s t roke volume of 7 6 ml; ( 3 ) the s y s t o l i c t o d i a s t o l i c r a t i o i s 1 : 2 thus favor- ing TIAH f i l l i n g ; ( 4 ) the TIAH incorporates b iopros the t ic t r i - l e a f l e t valves; ( 5 ) blood i s e jec ted by compression o f t he blood sac from b o t h s ides r e su l t i ng in a cen t r ipe t a l e jec t ior . through the o u t l e t valves; ( 6 ) the device wi l l be powered by e l e c t r i c a l energy t h a t i s transduced through the skin a n d no wires or tubes will penetrate the p a t i e n t ' s sk in .

Design of the TIAH

Hua Gao, Lin Gao, Robert J . Flemma, Carl W . Christensen, Donald H. Schmidt 301 Bei j i n g General Hospi ta l , Bei j i n g , China; Sinai Samaritan Medical Center, Milwaukee, WI LlSA

DEVELOPMENT OF BIOREACTORS FOR LIVER

FOR HEPATOCYTE CULTURE

treatment in liver support systems, cell culture conditions in these reactors have an important meaning. To study if bioreactors need I. oxygen supply, 11. hormone supply, ID. pH- regulation, IV. cell attachment, V.attachment membranes, we investigated the detoxification of ammonia and the synthesis of urea with primary isolated rat hepatocytes.

To find out suitable membranes for cell attachment into bioreactors, 8 cellulose (Cuprophane), 3 polyamide, and 3 polypropylene membranes were investigated.

Alkalotic pH in the medium reduces cell viability. Supply of hepatocyte stimulating hormones has no significant influence on ammonia metabolism. The 24h reduction of ammonia from an initial 350 pM to under 100pM could be done twice by cells in suspension culture, and six times by cells in adhesion culture.

Adhesion of hepatocytes onto the different membranes was variable. Whereas Cuprophane seems to be unsuitable for cell attachment, polyamide and polypropylene allows considerable cell adhesion.

Conclusions: Bioreactors need oxygenation of the hepatocytes if perfused with venous blood. A continous monitoring of pH is important. Hormone supply seems not to be necessary. Since attachment of hepatocytes to a substrate promotes their active phase in vitro, a major goal in the development of bioreactors is the development of a large cell adhesion surface.

Using the investigated polyamide or polypropylene membranes in bioreactors for an enhancement of the cell adhesion surface and as a plasma separation membrane, cell attachment and cellular immunoisolation can be. combined in one element.

J.Gerlach, H.H.Schauwecker. P. Stoll, K. KlOppel, Chirurgische Klinik, UKRVI Charlottenburg, Freie Universiat Berlin, W Germany

SUPPORT SYSTEMS - STUDY OF REQIREMENTS

In an approach to develop bioreactors for long term

Increasing oxygen pressure promotes cell function.

Arlificial Organs, Vol. 13, No. 4, 1989


73 INTRAVJINOUS VERSUS SUBCUTAIEOUS ADUINISTRATION OF RECOMBINANT ERYTHROPOIETIN: A COMPARATIVE STUDY OF EFFECTIWNESS AND SIDE EFFECTS Theoretical considerations suggest that a more constant marrow stimulation as with S.C. administration could enhance r-EPO effectiveness. In a prospective study 2 groups of dialysis pts (n=16 in each group) were treated either S.C. or i.v. with r-EPO. Both groups received initially 50 U/kg b.w., adjustments were done in 4 weeks intervals according to the increase of Hb levels. The slope of the Hb curves, the dosage required to increase or maintain a target Hb level and the side effects of therapy were monitored. In the first 4 weeks the increase of Hb-levels was similar (Hb in the iv-group rose from 7.23- +1.1 to 8.56+1.55 in the sc-group from 7.96+0.9 to 8.51+1.13) . After six weeks i.v. treated pts required an increase of the r-EPO dose to maintain a constant Hb increase whereas in the S.C. group r-EPO even had to be reduced. After 3 and 6 month the r-EPO dose in the sc-group was significantly lower then in the i.v. group (~(0.05 and p<O.O5 respectively) whereas the Hb-levels in both groups were almost identical. As general side effect of r-EPO increases of blood pressure occurred with similar frequency in both groups, however, unspecific side effects as bone pain or fluelike syndromes occurred only in the iv group. It is concluded that S.C. instead of i.v. administration of r-EPO results in 1) a reduced dose requirement to achieve and maintain desired Hb levels, 2) S.C. administration of r-EPO has significantly less undesirable effects. -- H. Graf, U. Barnas, U. Watzinger, F. Meisl, G. Mayer. 2nd Dept. of Medicine, Univ. of Vienna, and Wilhelminenspital, Vienna, Austria

7s U?PLANTATION OF TEXTURED SURFACE LEFT VENTRICULAR ASSIST DETICES ITSLVAD) IN THE CALF - EVALUATION OF BIKX)D/BICMATERIAL INTERFACE

TSLVADs are being developed for proposed permanent clinical inplantation. A n essential requirement is a non- t hromboembo 1 i c haermtolggically stable blood contacting surface. '!helve T h e m Cardiosystems TSLVADs featuring integrally textured polyurethane (ITP) on the pusher plate surface and sintered titanium (ST) on the static housing have been implanted in 72.3kg (mean) calves for periods from 6 hours to 98 days. To augment neo-intiml development eight devices were seeded with 72 million (mean) bovine foetal fibroblasts prior to implantation. The seeded ITP develops a stable trilaminar neo-intim from nine days onwards containing viable seeded fibroblasts. On the seeded ST develops a thin acellular collagenous neo-intim. Non-seeded (N = 4 ) neo-intim on ITP and ST surfaces appears more proliferative. Platelet counts following implantation fell to 25% of pre-operative level by Day 2 with a rebound thrombocytosis by Day 7 and return to normal within 14 days. Platelet survival (I11 Indium and Gannm function multiple hit model) was significantly reduced at one mnth following implantation; mean normal survival 2.99 (N = 12) V 1.79 (N = 5) days (p<O.OOOl). RBC survival ( 5 1 CTrn-ome labelling) was not significantly altered one mnth following implantation. Neo-intiml linings warrant further evaluation as potential permanent bimterial/blccd contacting surfaces within LV assist devices. -~ T.R.Graham, D. Syndercombe-Court, P. S. Reynolds, V. Salih, A. coumbe, C. T. Lewis. The London Hospital, London, U.K.

74 BLKlD/BICWYTERIAL INTERFACE EVALUATION WITHIN PERRlSION CHAMBERS IN AN IN VITRO C I R L W R Y LOIP

Various bi omter i a1 s and their mdifications are being evaluated for long term use in cardiac and vascular prostheses. A circulatory l m p utilising four seperate perfusion chambers has been designed for the in vitro evaluation of these biomterials in a homeostatic blood environment. Blood is propelled by a Watson-Marlow roller pump through a Scimed membrane oxygenator (0800-2A) up to a resemoir. Flow (?00-400mls per min) varied by reservoir height proceeds through a rotometer to the flat perfusion chanbers; returning to the pump via a heated water bath. Heparin bonded silastic tubing is used. The polymethyl methacrylate transparent perfusion chambers have a central depression on to which fits a knob with biomterial placed in a groove 132 x lorn) upm the surface. Altered flow patterns m y be induced by rotating the knob. The parallel placement of these chambers allows the sequential removal and study of the biomaterial whilst mintaining identical test conditions (LM,EM). Within this system m y be evaluated cellular seeding options of bimterials. Haemtological studies (cell counts, radioisotope studies, effect of anti-platelet agents) can be performed on human b i d due to the small prime volume of this circuit (400mls).

T.R.Graham, P.S.Reynolds, V.Salih, A. Coumbe, C.L.Berry, C.T.Lewis. The London Hospital, London, UK.

76 EVALUATION OF TMTURED BICWTERIAL SURFACES DURING CLINICAL USE OF AN IMPLANTABLE LEFT VENTRICULAR ASSIST DEVICE (LVAD)

The T h e m Cardiosystems(TC1) inplantable LVAD features an integrally textured polyurethane (ITP) diaphragm and sintered titanium (ST) on the rigid housing to encourage neo-intiml development. The TCI LVAD was implanted in twelve mle patients (Age range 17-59) between 1986 and 1988. Duration of implantation ranged from 4-41 days. No clinical thromboembolic event or pump related thromboenhlism evident at necropsy (N = 6 ) occurred. Explanted devices were free of thrombus and calcification. Lining samples for light and electron microscopy were collected from identical regions of ST and ITP surfaces - areas of high flexlshear and low flexlshear rate conditions. On the ST surface was deposited islands of collagenous tissue amongst adjacent tissue composed of conpact fibrin. On the ITP surface by Day 13 undifferentiated cells populate the surface of the developing collagenous neo-intim. By 4 1 days the surface cell density increased, the cells becoming spindle shaped and orientated in the high shear/flex area. Imnohistochemical techniques suggest that these cells are of mesenchyml origin. Textured blood contacting surfaces appear satisfactory in preliminary clinical use of this device.

T. R. Graham(l1, K. Dasse(Z), O.H. Frazier(3), J. Macoviak(4), A. Coumbe(l), C T Lewis(1). The London Hospital, London U K ( 1 ) , Themcardio Systems Inc, Woburn Mass., UsA.(2), Texas Heart Institution, Texas, USA(3),& Washington Hospital Centre, Washington Dc, USA.

ArtificiaI Organs, Vol. 13, No. 4 , 1989


77 THEM3 CARDIOSYSTEMS INC. EL-CWICAL LEFT VENTRICULAR ASSIST SYSTEM (LVASI FOR INTERMEDIATE CLINICAL USE

A percutaneous electromechanical LV assist system for use in ambulatory patients is being develod. This implantable system is intended to bridge the gap between short term systems and the permanent electromechanical LV assist systems presently undergoing reliability testing.

An 80ml pusher plate blood pump with integrally textured polyurethane and sintered titanium blmd contacting surfaces is powered by a smll electric mtor. Electrical power and vent lines pass across the skin via implantable polyurethane skin buttons. The min power source and control system is designed to be carried in a shoulder harness beneath the patients clothing. A battery pack weighing 1.2kg will power the device for ten hours at five litres per minute flow and 130/80mnHg pressure. The mtor current wave form is analysed to automtically adjust the rate so as to mintain plurp, stroke volume near maximum. A fixed basal rate is available as back up.

In vitro testing has demonstrated nine month reliability of six systems. In vivo testing with flows of 6 litres per minute for longer than three months have been domnstrated in calves without any infection at the transcutaneous line sites.

T R Graham, P S Withington, W Clay*, V Poirier‘, C T Lewis. The London Hospital, London, UK & *Them Cardiosystems Inc, Woburn, Mass., USA

79 UNLOADING THE FAILING HEART

We created a semiacute left ventricular failure model in six weanling pigs using a 2- stage procedure. Left ventricular failure was c h a r a c t e r i z e d by l e f t v e n t r i c u l a r e n d - diastolic diameters that were increased by 8 to 15% from control. Left ventricular end- diastolic pressures and left atrial pressures were also increased. Baseline aortic pressure means ranged from 50 - 100 mm Hg and were depressed to 30 - 60 mm Hg during failure. Cardiac output decreased from 2.5 - 3.0 L/min during baseline to the range of 700 - 1750 ml/min. We were able to reduce left atrial p ressures , l e f t vent r icu lar end-d ias to l ic diameters and left ventricular end-diastolic pressures by pumping relatively small volumes of blood (50 - 150 ml/min) out of the left atrium and into the aorta. These preliminary experiments seem to indicate that it is possible to unload the failing left ventricle with relatively low left ventricular assist device flows. If these results can be duplicated in a chronic congestive left heart failure model we may be able to appreciably reduce design criteria for left ventricular assist devices. Gross. D.R., Mulligan, L.J., Hays, S.M. and Hwang, N.H.C. Physiol. and Applied Physics Lab., Dept. Vet. Physiol. & Pharm., Texas A&M Univ., College Station, TX, USA

78

80

EXPERIENCE WITH MEDTRONIC HRNCCCK PORCINE XEN0”uRAFT VALVES IN AN IMPLANUBLE LEFT VWI’RICULAR ASSIST DEVICE (LVAD)

The T h e m Cardiosystems Inc. (TCI) textured surface implantable pneumatic pusher plate LVAD utilises inflow and outflow conduits containing 25m Medtronic Hancock porcine xenograft valves. Between January 1986 and November 1988 fifteen intermediate clinical implants have been performed in the UK and USA. Seven patients (47%) proceeded successfully to transplantatinn (duration of support(DS) mean 26.4days(SM 4.6), range 7-41days). Six (40%) died with the LVAD in situ (DS mean 8.7days (3.1), range 1-25days). One patient currently has a device in situ (DS 120 days); he is well and awaits transplantation. No haemlysis or clinical thro-lic episodes have been noted during device use. There was no evidence of device related distal thromboembolism at necroscopy. Examination of the explanted valves was satisfactory with no evidence of leaflet tears, calcification or endocarditis. Anti-coagulation regimes including Warfarin, Heparin and anti-platelet agents have been used. Based on this experience and other extensive clinical data available these valves are being utilised in LV assist systems being developed for permanent implantation.

T R Graham(l), 0 H Frazier(2), J Macoviak(3), K Dasse(4), V Poirier(4), C T Lewis(1). The London Hospital, London UK(11, Texas Heart Institution, Texas, USA(21, Washington Hospital Centre, Washington Dc, USA(3), & T h e m Cardiosystems Inc, Woburn Mass., USA(4).

A PROPOSAL FOR A RESPIRATION SIMULATOR Phvsicialis workina in Intensive Care LT.- 1 rrrts, in iiutritlanal and mctaholiz dc P a i- t m E ii t s du 1- in q surserv, iiicreasinalv rely i t 1 1 expired aas analvsis. Monitorins devices of metabolic Pulmonarv aas exchanse dre fl-iciueiitly used in those Care Units. ~edsidc de-<ices to assess the instrument rcliabilitv are lackins. We made an easilv assembled device to be temsorarilv connected to a volumetric VEiitllatGr and to a roller blood pump, bczth of which are instruments available in the clinical units where the respiratcrs monitorins is u s u a l l y Performed. The 1-esultiilq svstem works as a simulator either of spontaneous breathins 01- of mechanicallv ventilate6 patient respiration. The simulated respiration can be very u s e f u l in assessins the reliabilitv of monitorina svstems, includina those for breath-bv-breath aiialvsis for variable ventilation parameters i.e. breathins rate, tidal volume, minute/volume and inspiratorv O:, concentration, The proposed respiration simulator can be an useful device f o r testiiis ciiiferent monitorina systems in the Intensive Care Units. DANI.ELE GUI. PAOLO COTOGNI Surcrical Intensive Care Unit DePt of Surserv Celltro di Studio per la Fisiopatolosia dello Shock. C.N.R.- Catholic Univei-sitv L.ao A. Gemelli. 8- 00168 Rome, Italv.

r an a t s t he t is t s

- _

Art5cial Organs, Vol. 13, No. 4, 1989

ABSTRACTS OF THE Vl l th WORLD CONGRESS 303

81

83

Stimulus-Responsive Characteristics and Oral Drug Release Applications of Ca-Alginate Gels

Tre reversible swelling c i ia-Alginare oeis Wnlch were prepared b v

dripwise addition o f the Na-Alginate solutions ( 1 , 3, 5 X w l v ) into

ih? t3'Cl: media were investigaled against t o two different stimulus,

i .e , pt i arld tempers luw They Here ihanged in the range o f 2-8 and

4-57'i, respectivelv. The release of model drug. riboflavin. i r o m

t h w gels were studied a t d i f ferent pH and temperature conditions

and also in ar t i f ic ia l stomach and in intestine media. The drug r e l e a x

kiiirtics were ivdluated rnatl~ernatlcsl ly. The ioiriodr,alive results

inllirared tnat. the swellma rates and also the resultant swelling

values o f gels depend on the init ial cnncentratinns o f 14s-alginate.

crosslinker and CaC12. pH and ternpersture. The gels show "gel-sol"

LraiIsitiun i r l thr rdnye o f pH. 26-2.8. The riboflavin release f rom

gel: i n oiliuwm and also relaxation-controlled above the transition

pt l ~fal iJP and nnly d l f f iJSi in-COnlr@~~~d under this pti The a18jinate gels

;re non-swell3ble in ~ r t i i r c i ~ l stomach media and they releme only

30 X o i the ! o t d druy ir~ 3 r1oui.s. Ttirse yels I'riedse dl Ltib diwy i i t

inxst ina l medium less than 5 minutes a5 3 result o i the degradation

of ?els \n this modium

ti. GUMUSDERELID~LU, A TUIICEL, M. KIREMITCI. E. PISKIH Hace:tepe Uniusrsitv, Chemical Engineering Dept , Ankara. Turkev

"ON-LINE HEMOFILTRATI0N":CLINICAL USE OF VOLUMETRIC UF CONTROLLER FRESENIUS A2006 HDF/M Bicarbonate A2008C a l ready k i t t e d for " o n - l i n e "

H3F has been modified f o r "on-line" hemofil tration (HF):l ' )Tangential f i l t r a t i o n of d i a lysa t e ( 7 X rejection)(ASAHI PAN 250) ; 2')Tangential f i l t r a t i o n of RI f l u i d ( A S A H I PAN 150) ; 3') Manual by-pass of d i a lysa t e us ing UF con t ro l l e r f o r UF monitoring and production of R I f l u i d .

Modified A2008 used in 4 pa t i en t s already t r ea t ed by HF during 1 month 160 ses s ions ) : 1") :Blood flow = 400 t o 500 m l / m i n ; 2 ' ) :UF = 30 t o 35 l i t e r s / s e s s i o n ; 3 ') :polysulfone membranes ( F 8 0 ) . P a i r e d t-test a n a l y s i s f o r sess ion d u r a t i o n ( S D ) , mean Uf volume (V.Uf) , U f ra te ( Q . U f ) , weight l o s s error ( W L . e ) and small molecules before HF between A20@8 HF and previous SARTORIUS 40005 HF ses s ions .

( l imulus test , s e n s i t i v i t y l imit = 0 . 1 3 U E / m l ) before RI f i l t r a t i o n .

t r e a t a l l pa t i en t s e i ther w i t h HD, HDF or HF without any spec ia l d i sposable and w i t h s a fe ty

f3 r nurses no r i n rou t ine use of A2008 i n a s t indard HF program. ____ H4AS.T, H i l l i o n . D , Uzan.M, P e r t u i s e t . N , C a l e w i e r . P Pr>issy H o s p i t a l , Evry c l i n i c and F r e s e n i u s , PRANCE

CONCLUSION: F r e s e n i u s A2008 C is usable t o

Hi tPlEe6arrda ~ ~ c ~ ~ ~ ~ n F i ~ f o e Y ~ ~ H t ~ ~ ~ ~ :AsAasi%ftE2$

82

84

PLASMA SEPARATION USING A NEW POLYAMIDE MEMBRANE AND PULSTDJG INLET BLOOD FLOW.

Polyamide experimental prototype plasma filters and bovine blood collected on A.C.D. have been used for plasma separation experiments with steady and pulsating inlet blood flows. For steady blood flow, we found that 600 ml of plasma can be collected without hemolysis in about 30 mn at an entry blood flow rate of 80-100 ml/mn and at about 100 mm Hg of transmembrane pressure, while using pulsating entry flow, at a frequency of pulsations between 1.5 to 1.7 Hz and displaced volume of about 1.5 ml, the collection time was 24 mn i.e. about 25% increase in filtration flow rate. The increase in filtration rate was more at lower entry blood flow rates, for example, at 60 d / m n of enhy blood flow, this increase was more than 50%. The filtration flow rates using pulsating entry flow were also obtained with polypropylene filters under identical experimental conditions and we obtained about 27% and 46% increase in filtation rate at 100 mVmn and 60 d / m n entry blood flow rates. We observed that filtration rate was independant of time with pulsating flow and a little decrease in total protein quantity (from 81fl to 7 6 g ) during 150 mn of filtration. Also, we observed two unwanted factors, 1. elongation of fibers (about 5%) while rinsing and 2. hemolysis in the very begining of separation.

B.B. Guuta and M.Y. Jaffrin UA CNRS 858, Universitk de Technologie Compitgne, 60206 Compikgne, France

A NEW TECHNIQUE FOR B R I D G I N G TO HEART TRAXS- PLANTATION-PRACTICABILITY OF MONOVENTRICULARI- ZATION OF BILATERAL VENTRICLES KITH LVAD

The prognosis of post myocardial infarction ventricular septa1 perforation(VSP) with mitral regurgitation(r4R) is remarkablly poor.We speculate that the failing heart can be strong enough to sustain the pulmonary circulation when the mitral valve is closed and the bilateral ventricles communicating through VSP work as the right ventricle. A left ventricular assist device(LVAD) maintains the systemic circulation.

6 canine models with VSP and MR were monovent- ricularized with mitral valve closure and instituted with LVAD between the left atrium and the femoral artery. Hemodynamic state was evaluated (A) in intact heart, (B) with VSP and MR, and (C) after monoventricularization.

Cardiac output:

Mean aortic oressure: (A) 94.0 ? 25.5 (mmHg) (B) 3 2 . 0 2 8.6 ( C ) 68.2 + 19.1 d

P C 0 .005 4 PC 0 . 0 5 ] '" - -

Left atrial pressure, central venous pressure and mean pulmonary artery pressure are all at the same level in (A) and (C).

system for bridging to cardiac transplantation in certain patients with VSP and MR who are to be candidates for transplantation because of irreversible cardiac dysfunction. Yoshiyuki Haga,Ryohei Yozu,Yasuhiro Soma,Shi%eyuki Takeuchi, Tadashi Inoue, Susumu Tanaka". Dept,. of Surg., Keio Univ., Tokyo, andY2nd Dept. of Surg., National Defense lledical College, Saitama, Japan

Monoventricularization with LV.0 can be a new

Artificial Organs, Vol. 13. N o . 4, 1989


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87

THE SPINDLE PUMP - A NONPULSATILE BLOOD FOR ASSISTED CIRCULATION

The pulsless spindle pump was developed to prevent the main problems of nonpulsatile blood pumps, i.e. traumatic hemolysis, thrombus formation and sealing difficulties. To deal with these problems we chose a premise whereby the essential aim was to achieve sufficient volume output a1 low rpm rates to minimize blood trauma by proper design.

The result of these considerations was a very simple blond pump, consisting o f a spindle with 3 windings, an U-shaped Plexiglas housing with 2 connectors for inflow and outflow cannulas and an electric motor. Many modifications o f this pump- concept were necessary to fulfill the goals reite- rated before, whereby the main difficulty was to find the adequate dimension of the spindle.

The prototype which now meets our goals has a spindle with an outer diameter of 4,44 cm, an inner diameter o f 2,75 cm and a pitch of 1 cm. In mock circulation the pump moves 6 liter of water/ min against 120 torr at 4800 rpm. In animal experiments these results were confirmed; depending on the arterial blood pressure, up to 4900 rpm were necessary to attain a nonpulsatile flow, i.e. between 6 and 9 liters of blood were circulated per minute. The traumatic hemolysis remained within desired limits and stayed within the norm or slightly above during longer experiments (up to 63 hours o f pumping duration).

iosef Haqef, Friedrich Brandstaetter, Otto Dietze,

I. Universitatsklinik f. Chirurqie, University o f ngrid Kol e r , Felix Unger

Innsbruck, Innsbruck - Austria

HEHOPURIFICATlON AS A TREATHENT OF HYONEPHROPATHI C METABOLIC SYNDROME AFTER SURGERY FOR VASUCULAR EHERGENCIES

Hyonephropathic metabolic syndome(HNHS) is a serious condition, often encountered after operations for acute arterial obstructive diseases. Host patients die due to complications of renal, hepatic, or other organ failure. Hemopurification becomes often necessary. This condition is believed to be caused mainly by the effects of toxic substances, such as myoglobin. potasium, etc. We propose a new criteria of HNNS. The results of hemopurrification are reported. [HATERIALS AND HETHOUS] For the last 5 years, some form of hemopurification were performed on eight patients of MNHS. All of the8 had high serum myoglobin level. Renal and hepatic failure existed frequently. Hemodialysis was performed in four patients. Plasma exchange was performed in one. Irrigation of the artery of the diseased extremity by infusion and washing out of venous blood, w a s performed to remove toxic substances in four. Hemabsorption of venous blood of the diseased extreaity was performed on one. [RESULTS AND CONLUSIONS] Five patients survived, with a mortality of 37.51. Frequent and early application of hernopurification is thought to be essential. The serum iyoglobin level decreased after hernoabsorption and arterial irrigation. Therefore, these treatments were thought t o be effective in reducing toxic substances, as far as the removal of myoglobin concerned.

Y. Haraguchi. Y. Hatsuhasi. 8 . Ooaara. U. Kirita, H. Sakai. K. Hayashi, 8. Kubota, S. kern and *T. Ishihara Dep of ICU-Surgery, Tokyo Police Bospital. Tokyo, Japan, aeP of Surgery. Sbirabigebashi Eospital, Tokyo. J ~ P M

86

88

TREATHENT OF ACUTE FULHINANT PANCREATITIS BY HEHOPURI F I CATION

Acute fulminant pancreastitis is a disease of high mortality. Renal or hepatic failure and other severe metabolic disorders are related to death. Ye think that hemopurification is useful in improving these serious condtions. Our experience is reported. [MATERIALS] Sixteen cases of acute pancreatitis were studied. Ten had severe pancreatitis. while six were diagnosed to be of less severe degree. [RESULTS]Among severe pancreatitis, nine(9OX) had acute renal failure or severe metabolic disorders, such as acidosis, electolyte inbalance, rhabdomyo- lysis, etc. The mortality was 50% in severe pancreatitis, while none of less severe group died. Hemo- purification became necessary in eight of severe pancreatitis. Hemodialysis, plasma exchange, peritoneal dialysis and hemoabsorption was performed in 2, 4 , 2 and 1 case, respectively. Nafamostat mesilate was used as anitcoagulant usually. Most of cases who survived (three out of four) were treated by plasma exchange. From the viewpoint of plasma exchange, three out of four patients(75X) survived and one died. After plasma exchange, serum level of proteolytic enzymes and other metabolic abnormalities tended to improve. [CONCLUSIONSITo reduce the high mortality of acute severe pancreatitis. intensive care, including hemopurification should be performed aggressively.

Y. Haraguchi, S. Hasegawa. H. Kirita. H. Oosawa, A . Hizuuchi, M. Sakai and 'T. Ishihara Dept of ICU, Tokyo Police Hospital, Tokyo, Japan 'Shirahigebashi Hospital, Tokyo, Japan

USE OF LEFT HEART BYPASS WITH THE ANTHRON TUBE

SELDING AORTIC ANEURYSMS WITHOUT HEPARINIZATION Prosthetic graft replacements for descending thoracic and thoraco-abdominal aortic aneurysms were successfully performed by using a left heart bypass the Bio-pump without total body heparin- i zati on. The study included 22 patients, 17 males and 5 females, with ages ranging from 23 to 73 years, mean 52.9 years. The types of the aneurysms were IIIb dissection in9, I dissection in 1,sclerotic descending thoracic in 9, distal arch and descending in 1 , and sclerotic thoraco-abdominal in 2 cases. The mean duration o f the left heart bypass was 93 minutes, the maximal bypass flow rate was 2.2k0.4 l/min., and during the bypass the distal mean pressure was more than 60 mHg., and urinary output was excellent. There were no serious complications due to the left heart bypass. Postoperatively, there were minimal or no significant changes in platelets count. There were two hospital deaths, and one late death,and the other 19 patients are well. For this type of aneurysmectomy, the above described left heart bypass without heparinization is the most beneficial procedure from the stand- point of decreasing preload and afterload, main- taing the diastolic blood flow,and eliminating complications due to heparinization during the aortic cross-clamp.

AIiD THE BIO-PUMP IN SURGICAL TREATMENT FOR DE-

Akimasa Hashimoto, Kohki Tsuchida, and Hitoshi Koyanagi Dept. of Cardiovasc. Surg., Heart Institute of Japan, Tokyo Women's Medical College,Tokyo,Japan

Artificitrl Organs. Yol. 13, No. 4, 1989


89 A NEWLY DESIGNED PNEUMATIC-PULSE-PUMP-MEMBRANE 90 CXYGENATOR

I n o r d e r t o s h o r t e n t h e e x t r a c o r p o r e a l c i r c u l a t i o n c i r c u i t a n d t o i n c r e a s e t h e e f f i c i e n c y o f o x y g e n a t i o n , a new m e m b r a n e cxygenator combined w i t h a pump was designed.

The membrane w a s formed w i t h the s i l i c o n e tube (0.3 m m i n t e r n a l d i a m e t e r , 0.63 m m e x t e r n a l d i a m e t e r ) . I n t h e m i n i a t u r e model , 1 7 0 0 p i e c e s (200 m m l e n g t h e a c h ) of t u b e w e r e b u n d l e d and packed i n a p o l y c a r b o n a t e - c y l i n d e r w i t h e l a s t i c s i l i c o n e f i l l e r s . I n b o t h i n f l o w a n d o u t f l o w s i d e s of t h e c y l i n d e r , b a l l va lves were equipped. The t o t a l a v a i l a b l e a r e a of t h e membrane i s 0.19 m 2 . I n t h i s model, t h e membrane was pneumat ica l ly d r i v e n w i t h t h e r e c i p r o c a t i n g pump i n p e r f o r m a n c e t e s t s , i n w h i c h 1 0 0 X o x y g e n c i r c u l a t e d i n t h e g a s s i d e ( o u t s i d e o f t h e tube) .

T h e c o m p l i a n c e t e s t s h o w s t h a t a 6.7 % e e c r e a s e i n t h e volume o f b l o o d s i d e ( i n s i d e of t h e t u b e ) i s made by 0.5 atm p r e s s u r e d i f f e r e n c e across t h e membrane. The g a s p e r m e a b i l i t y t e s t ~ h o w s t h a t 13.5 ml/min oxygen gas i s permeated by 0.5 atm p r e s s u r e d i f f e r e n c e a t Z4 'C . The mock t e s t shows that t h e oxygen t e n s i o n i n c r e a s e s from 217 mmHg a t t h e i n l e t t o 711 mmHg a t t h e o u t l e t c f t h e o x y g e n a t o r when 29 m l / m i n (0.5 m l s t r o k e v o l u m e ) s a l i n e s o l u t i o n i s pumped. The performance h a s been maintained i n an imal t e s t s . S h i g e h i r o Hashimoto, S e i i c h i Tominaga", Minoru Yoshida? x , Yasunori Sasaki** Dept. o f B i o e n g i n e e r i n g and " T h o r a c i c S u r g e r y , S c h o o l o f M e d i c i n e , K i t a s a t o U n i v e r s i t y , Saga m i hara , Japan ' " M a t e r i a l s Dept., E n g i n e e r i n g D i v i s i o n , N O K Ccrpora t ion , Fuj i sawa, Japan

91 COMPLIANT SMALL-CALIBERED VASCULAR GRAFT MADE OF 92 MICROPOROUS POLYURETHANE - I N VITRO AND IN V I V O MECHANICAL EVALUATION

C o n s i d e r i n g t h a t compl iance ma tch ing i s a key f a c t o r f o r t h e s u c c e s s f u l development o f s m a l l - c a l i b e r e d v a s c u l a r g r a f t s , s t a b i l i t y o f t h e s t i f f n e s s o f a newly developed s m a l l d iamete r p o l y u r e t h a n e g r a f t (3mm I D ) was s t u d i e d by l o n g - t e r m f a t i g u e t e s t i n g and animal i m p l a n t a t i o n . The m a t e r i a l i s a segmented po lyu re thane con- t a i n i n g p o l y d i m e t h y l s i l o x a n e (13% by w t ) i n t h e main c h a i n . Porous c o n d u i t s were f a b r i c a t e d o f t ,his m a t e r i a l by a phase s e p a r a t i o n techn ique , t h e i r o u t e r s u r f a c e s be ing covered w i t h p o l y e s t e r n e t . G r a f t s t i f f n e s s was eva lua ted by measur ing t,he s t i f f n e s s parameter B which i s e q u i v a l e n t t o t h e mean s l o p e o f a p ressu re -d iamete r cu rve i n t h e p h y s i o l o g i c a l p ressu re range.

The g r a f t s have s i m i l a r s t i f f n e s s (B=15.3+0.1) t,o t h e m idd le -aged human femora l a r t e r i e s (16.853.9) b e f o r e t e s t i n g . I n v i t r o l o n g - t e r m c y c l i c p r e s s u r i z a t i o n t e s t s between 60 and 16OmmHg a t 5Hz i n 37°C s a l i n e s o l u t i o n s l i g h t l y i n c r e a s e d B-va lue (7 .6% a t 10 rnos). A f t e r i m - p l a n t e d i n t o mongrel dogs as t h e s u b s t i t u t e s o f t h e c a r o t i d a r t e r i e s (40mm long ) f o r up t o 98 days (mean 69 days) , seven o u t o f e l e v e n g r a f t s ( 6 4 % ) were p a t e n t . The i m p l a n t a t i o n a l s o s l i g h t l y ' nc reased t h e g r a f t s t i f f n e s s (2 .7% a t 3 mos). However, t hese i n v i t r o and i n v i v o s t i f f n e s s changes were n o t s i g n i f i c a n t , i n d i c a t i n g t h a t t h e g r a f t s t i f f n e s s i s v e r y s t a b l e ove r l o n g p e r i o d . .- I:. Hayashi*, T. Sai to* , K. Takamizawa**, M. Sakuma#, T. N ish ibe# , T. Tanabe#, K . K i ra## , K. H i ramatsu##, and K. Kondo##, *Res. I n s t . App l . E l e c t r . , #Sch. Med., Hokkaido Univ . , Sapporo 060, *"Nat. Card iovasc. C t r . Res. I n s t . , Osaka 565, t M a n e g a f u c h i Chem. Ind . , Osaka 530, Japan

EFFECT OF SINUSOIDALLY FLUCTUATING SHEAR RATE ON CLOT GROWTH

I n p u l s a t i l e f l o w s (e.g. i n arteries o r i n t h e f l o w pa ths of e x t r a c o r p o r e a l c i r c u l a t i o n powered by p u l s a t i l e pumps) , p e r i o d i c a l l y f l u c t u a t i n g s h e a r r a t e s a r e a p p l i e d t o t h e blood. I n o r d e r t o s t u d y q u a n t i t a t i v e l y c l o t g r o w t h i n p u l s a t i l e f l o w , t h e h y d r o d y n a m i c e f f e c t of p e r i o d i c a l l y f l u c t u a t i n g s h e a r r a t e s on c l o t g r o w t h h a s been i n v e s t i g a t e d i n v i t ro . Uniform s h e a r r a t e s were a p p l i e d t o a sample of canine blood which f i l l e d t h e s p a c e b e t w e e n a s t a t i o n a r y convex cone ( d i a m e t e r , 4 8 m n i ; a p e x a n g l e , 1 1 5 " ) a n d a r o t a t i n g concave cone. Both cones were made from t r a n s p a r e n t po lymethylmethacry la te t o enable t h e b l o o d s a m p l e t o be o b s e r v e d . T h e s e s h e a r r a t e s , w h i c h a r e p r o p o r t i o n a l t o t h e r o t a t i o n s p e e d of t h e c o n c a v e cone , w e r e p e r i o d i c a l l y f l u c t u a t e d w i t h v a r i o u s f l u c t u a t i n g c o n d i t i o n s ; t h e s h e a r r a t e between a maximum (<BOO s - ' ) and a minimum (>50 s- l ) w i t h t h e f requency of f l u c t u a t i o n being s i n u s o i d a l (C0.6 Hz). E v a l u a t i o n o f c l o t g r o w t h was d e r i v e d f r o m t h e c l o t t i n g r a t i o ( t h e volumetr ic f r a c t i o n of c l o t i n t h e whole b lood) , which was e x p e r i m e n t a l l y de te rmined from t h e r a t e of i n c r e a s e of f r i c t i o n a l t o r q u e between t h e two c o n e s . R e s u l t s s h o w t h a t c l o t t i n g r a t i o decreases when t h e t ime of a p p l i c a t i o n of lower ( < l o 0 s - ' ) s h e a r r a t e s i s m o d i f i e d b y i n t e r m i t t e n t a p p l i c a t i o n o f h i g h e r (>500 s - l ) s h e a r r a t e s . S h i g e h i r o H a s h i m o t o , Ken Yamauchi x , T a d a s h i Sasada* Dept. o f B i o e n g i n e e r i n g , S c h o o l o f M e d i c i n e , K i t a s a t o U n i v e r s i t y , Sagamihara, Japan " F a c u l t y of E n g i n e e r i n g , Tokyo I n s t i t u t e o f Technology, Tokyo, Japan

PSORIASIS PUSTULOSA AND MIXED CONNECTIVE TISSUE DISEASE TREATED W I T H APHERESIS THERAPY

To o b t a i n t h e c l i n i c a l e f f e c t s of a p h e r e s i s therapy , we i n v e s t i g a t e d immunological changes and s i d e e f f e c t s of t h i s therapy . Two p a t i e n t s were eva lua ted ; one w i t h p s o r i a s i s p u s t u l o s a and t h e o t h e r with m u l t i p l e s k i n ulcer of mixed connect ive t i s s u e d i s e a s e (PSStSLEtRA, h e r e a f t e r MCTD). I n t h e former, d e c r e a s e s of t h e immunoglobulin and t h e complement t o g e t h e r wi th t h e s i g n i f i c a n t improvement of exanthema were observed, which sugges ted t h e e l i m i n a t i o n of an t ibody. I n v e s t i g a t i n g the OKT 418 r a t i o , t h e i n c r e a s e of t h e suppressor T-cel l w a s observed, and t h e r e f o r e , a z a t h i o p r i n e was adminis te red t o suppress the rebound. The b e n e f i t i a l c l i n i c a l e f f e c t w a s ob ta ined . I n t h e l a t t e r , t h e pulse therapy w a s performed t o g e t h e r w i t h a p h e r e s i s therapy by which t h e e p i t h e l i a l i z a t i o n was obta ined . However, a t t h e r e c u r r e n c e 6 months l a te r , t h e u l c e r became i n f e c t i o u s and i n t r a c t a b l e . S ince a p h e r e s i s t h e r a p y does remove p a t h o l o g i c a l subs tances b u t n o t suppress t h e product ion of a n t i b o d i e s , t h e s a t i s f a c t o r y e f f e c t can h a r d l y be expected only w i t h a p h e r e s i s therapy . Therefore , t h e combined t rea tment was p r e f e r a b l e w i t h t h e c o n s i d e r a t i o n of t h e immunological f i n d i n g s .

Miho Hayashi, Hayashi Dermato logica l C l i n i c , Nobuhiko Koga, Taketoshi Nagano, Koga H o s p i t a l , Kurume City, Japan

Artificial Organs, Vol. 13, No . 4, 1989

306

1 Mean S.D

CONCLUSION:

ABSTRACTS OF THE VIIth WORLD CONGRESS

Cb (mg/l) Cr (mg/l) B2Mur(mg) SC

28.2 9.1 < 10 0 8.8 4 .6 -

93 BETAZMICROGLOBULIN REMOVAL IN HEMOOFILTRATION USING 94 CONTINUOUS HEMOFILTRATION (CHF) IN THE TREATMENT PMMA BKU 2.1 sqm. OF ANURIC MULTIPLE ORGAN FAILURE (MOF)

CHF has been applied to 28 anuric MDF patients in our institution since 1987. CHF was performed with double lumen catheter placed in femoral vein or subclavian vein as a blood access. A blood pump was used to control blood flow and an infusion pump was used to control ultrafiltration rate. Low molecular weight heparin or protease inhibitor was used as anticoagulant. Hemodialysis was performed when serum creatinine level exceeded 6 mg/dl. The duration of CHF ranged from 3 days to 21 days (average 11.5 days) and average filtration rate was 202 ml/hr. All the patients could tolerste CHF despite their unstable hemodynamic condition. There was no adverse effect o f CHF. The sufficiency rate of the energy intake with total parenteral nutrition (energy expenditure / energy intake) was significantly improved with CHF compared to that without CHF. Water and electrolytes abnormalities could he easily corrected with CHF. CHF was especially effective in the treatment of pulmonary edema caused by overhydration. CHF could also remove various humoral mediators, which have been claimed t o be causative factors o f MOF. These results indicate that CHF is a safe, easily-performable and effective hemopurification for the treatment of anuric MOF and may be widely applied in the field of critical care and emergency medicine.

Hiroyuki Hirasawa, Takao Sugai, Yoshio Ohtake, Shigeto Oda, Hidetoshi Shiga and Michio Odaka Dept. of Emergency and CCM, Dialysis Center Chiba University School of Med., Chiba, Japan

Hillion.D, U2an.M. Pertu1set.N. Haas.T, Bignet.J.M CHI Poissy and MEDITOR (Toray, France) 78303 Poissy FRANCE

95 ENDOSCOPIC OBSERVATION OF INTERNAL SURFACE OF 96 Ah EXPERIMENTAL STUDY ON EXTRACORPOREAL MEMBRANE SHUNT VESSEL AND ANGIOPLASTY OXYGENATION (ECHO) FOR NEWBORN

Recently cases of shunt trouble are increasing as the elongation of duration of hemodiali- sis. We observed the internal surface of shunt vessels using vascular endoscopy.

NETHOD. We observed internal surface of shunt vessels using industrial fiberscope made of quartz glass (diameter 0.7mm) and OLYhIPUS PF 27L (diameter 2.7mm). During observation, the arterial side of shunt vessels was occluded by balloon catheter and saline was flushed from the tip of the sheath to make lucid in shunt vessels. We attempted to do angioplasty using balloon catheter and/or Laser probe under the fiberscopic observation.

surface of shunt vessels, stenotic site, and blood clots clearly. Angioplasty under the fiberscopic observation was successfully and safely done. On occasion of shunt troubles, it is very usefu l t o observe vessel lumen in three dimensions by vascular endoscopy. In future, the application f o r its practical use will be promi sing.

RESULT. We were able to observe the internal

S.Hirotani,Y.Nakagawa,M.Kimikawa,T.Hayashi. I.Nakajima,H.Fujikawa,H.Honda,S.Fuchinoue, S.Teraoka,H.Touma,K.Ota. The Third Department of Surgery,Tokyo Women's Medical College Hospital

Two types of ECMO units for newborn respiratory failure were developed in our laboratory. One utilizes a roller pump for venoarterial bypass (V-A bypass) or venovenous bypass of a continuous perfusion system (continuous V-V bypass). Another unit utilizes a pneumatic driving system for venovenous bypass of a to-and-fro perfusion system (to-and-fro V-V bypass), which is performed easily by inserting a single cannula via the jugular vein.

The three types of bypasses were investigated experimentally by using puppies whose weights ranged from 2.5 to 5.0 kg. General anesthesia was maintained with hypoventilation and ECMO was started. Hemodynamics and blood gas were measured to evaluate the effect of ECMO. The three types of bypasses were perfomed for twelve hours t o examine the effect on the liver, lung and blood.

Conclusions were as follow : 1) Our ECMO units were safe and easily operated. 2) Hernodynamics during ECMO were stable and there were no differences btween three bypass methods. 3 ) A s t o the effect on the respiratory support, V-A bypass was most effective. 4 ) On the to-and-fro V-V bypass, oxygen transfer of 2.4 ml/kg/min was obtained with a bypass flow of 50 ml/kg/min. 5) The to-and-fro V-V bypass unit might be utilized clinically f o r the neonatal respiratory failure.

Katsuya Hisano, Tetsuya Ienaga, Toshio Sawamura, Shozo Matsuda, Masayoshi Okada, Kazuo Nakamura Surgical Department, Kobe University Hospital, Kobe, Japan


91

99


INHIBITION OF PLATELET ADHESION TO ARTIFICIAL SURFACES COATED WITH FIXED ENDOTHELIUM OR SUBENDOTHELIUM

Adverse blood material interaction is a recognized problem in the use of prosthetic devices. Although many biopolymers and coatings have shown promise, endothelium is still the only true hemocompatible interface. In the light of published studies, documenting that fixed blood vessels and valves exhibit greater hernocompatibility than biopolymers (e.g. fixed veins, bioprosthedc valves) the role of fixed, cultured endothelium on blood malerial interaction was investigated. Bovine endothelia! cells harvested fresh from bovine pulmonary artery under sterile conditions were seeded on polystyrene, glass or Biomer in medium M-199 containing fetal bovine serum, following well established techniques. Confluent endothelial cell monolayers or surfaces with denuded endothelium were fixed in 2% buffered glutaraldehyde and e.xposed to heparinized bovine blood for three hours with continuous mixing. Following this, the surfaces were rinsed with saline to remove non adherent blood components and then processed for scanning electron microscopy. No platelets were found adherent on either intact fixed endothelium or subendothelium, obtained by removing the endothelium by trypsin treatment. Under identical experimental conditions, exposure of control (wilhout endothelial cells) surfaces to heparinized blood resulted in significant activation of be blood and fibrin deposition.

These observations suggest that the presence of cultured endothelial cells after they have been fixed with glumaldehyde renders otherwise thrombogenetic surfaces more hemocompatible. This may explain, in part, the greater hemocompatibility of bioprostheses. Hernocompatibility of fixed endothelium is of considerable interest. since fixed cells are not easily dislodged and could provide a suitable coating for artificial devices.

S.H. Hofma, S.F. Mohammad. W.J. Kolff and D.B. Olsen Artificial Heart Res. Laboratory, Univ of Utah, Salt Lake City. Ulah, USA

.4LUMINUM:A NEEDLESS RISK FOR DIALYSIS PATIENTS?.

6 Years ago,we dec ided t o reduce d r a s t i c a l l y t h e p . 0 . Al!OH)3 in take iwe r e p l a c e d it by CaC03 p l u s ( i n a l e s s e r degree)Mg(OH)2;only e x c e p t i o - n a l l y Al(OH)3 was g iven a s t h i r d product . 25 Chronic p a t i e n t s were t h e i r own c o n t r o l s du- r i n g 2,000 d i a 1 y s i s : t h e p e r i o d ( I ) : 1 9 8 2 + 1983 WES compared wi th t h e p e r i o d ( I I ) : 1 9 8 7 + 1988. The r e s u 1 t s : P e r i o d I v e r s u s Per iod I1 : Serum l e v e l : p.0. i n t a k e : A1:25 v f s 6 .6 ug/l" 5.6 v f s 0.7" g / d ? : 5 . 3 v / s 5 . 0 mg ICa:9.9 v / s 9 .6 mg 0 .2 v / s 3.7" g / d ' d i t . D: 79 v / s 70 nmol / l 0 .4 v / s 0.3 mg/d !$g : 2 . 7 v / s 2 .7 mg% 0 . 2 v f s 1.4" g / d ?TY:1.9 v / s 1.5 pg/ml Alk.Phase:170 v / s 174 m U / m l .'- = p < 0.05 W e no ted a s i g n i f i c a n t d e c r e a s e i n A 1 b l o o d l e v e l . (Water t r e a t m e n t be ing unchanged).The c o n t r o l of phosphatemia and of parathormone l e v e l remained p e r f e c t ; no impor tan t s i d e e f f e c t s of Ca and Mg were noted . ? r e d i a l y s i s u r e a and c r e a t i n i n l e v e l s , i n t e r d i a l y - t i c weightga in and i d e a l weight remained unchanged. Conclusion:A1(OH)3 i n t a k e is a n e e d l e s s r i s k f o r :he p a t i e n t s ' h e a 1 t h ; c o n t r o l of phosphatemia can 'it: o b t a i n e d by CaC03,and Mg(OH)2,plus r a r e l y a ! ; i n a l l amount of Al(OH)3.Regular c o n t r o l of c a l - w m i a is necessary and a l s o a n ad jus tment of t h e . r i t . D i n t a k e .

!< Hombrouckx,A.M. Bogaert , F.Leroy. D i a l y s i s Uni t ,Kl in iek Hogerlucht,Ronse,Belgium

98 THE LIMITATIONS OF SHORT DIALYSIS ARE THE INDICATIONS FOR DAILY DIALYSIS.

c iency is h i g h e s t i n t h e f i r s t and wors t i n t h e l a s t hour of d i a l y s i s , a n d t h a t t h e d i a l y s i s com- p l i c a t i o n s s u c h as cramps,headache,nausea,hypo- t e n s i o n and shock occur p r e f e r e n t i a l l y dur ing t h e l a s t hour .This is caused by t h e v a s c u l a r r e f i l - l i n g which is n o t as f a s t as t h e d i a l y s i s removal of water and s o l u b l e s . T h i s shortcoming however.can be overcome by d a i l y u l t r a s h o r t dialysis(DUD):the e f f i c i e n c y of a d a i - l y d i a l y s i s s e s s i o n of 1 .5 hour exceeds t h e d i a - l y s i s e f f i c i e n c y of 3 t i m e s 4 hours week1y;fur- t h e r o n DUD is a much b e t t e r t o l e r a t e d , a n d more p h y s i o l o g i c a l method of e p u r a t i o n . Because of p r a c t i c a l r e a s o n s , t h i s d i a l y s i s s t r a - t e g y has t o be ??served f o r home d i a l y s i s pa- t i e n t s . T h a t is why w e developed a v e r y easy ,s im- p le ,cheap and s a f e d i a l y s i s a p p a r a t u s f o r DUD t o be performed hy t h e p a t i e n t h i m s e l f , w i t h o u t as- s i s t a n c e of a p a r t n e r . I t c o n s i s t s of a b i d i r e c - t i o n a l bloodpump,accumulat;ng blood d u r i n g one h a l f of t h e c y c l u s i n an accumula t ion bag placed above t h e a r t i f i c i a l kidney(AK),and emptying t h i s bag a g a i n through t h e AK d u r i n g t h e second phase . The s t e e r i n g of t h e pump in one o r o t h e r d i r e c - t i o n is c o n t r o l l e d by t h e weight of t h e accumula- a t i o n bag,measured by an e l e c t r o n i c ba lance .Al- ready more t h a n 2000 d i a l y s i s s e s s i o n s have been performed w i t h t h e f i r s t p r o t o t y p e s , w i t h e x c e l l e n t c l i n i c a l and b iochemica l r e s u l t s .

The e x p e r i e n c e l e a r n e d t h a t t h e d i a l y s i s e f f i -

R.Hombrouckx,A.M.Bogaert,F.Leroy. D i a l y s i s U n i t , K l i n i e k Hogerlucht,Ronse,Belgium.

100 PREVENTION OF HEMODIALYSIS-INDUCED THROMBOCYTOPEN1A;EFFECT OF NAFAMOSTAT MESILATE(FUT-175)

FUT-175;one of p r o t e a s e i n h i b i t o r s , i s r e p o r t e d a s a u s e f u l a n t i c o a g u l a n t f o r hernodialysis e s p e c i a l l y i n p a t i e n t s w i t h b l e e d i n g tendency. To examine t h e e f f e c t of FUT-175 on e x t r a c o r p o r e a l th rombosis , w e used FUT-175 i n two c a s e s wi th s e v e r e hemodialysis- induced thrombocytopenia .

Two c a s e s newly induced t o hemodia lys i s due t o c h r o n i c r e n a l f a i l u r e developed s e v e r e c l o t t i n g i n d i a l y z e r s under normal or high-dose h e p a r i n i z a t i o n . F i f t e e n minutes a f t e r t h e i n i t i a t i o n of d i a l y s i s , a marked d e c r e a s e of t h e p l a t e l e t counts(59-72%) w a s found and i n one c a s e , d e p o s i t i o n of p l a t e l e t s and t h e i r microaggrega tes were demonst ra ted on t h e s u r f a c e o f t h e cuprophane membrane by e l e c t r o n microscopy. Changes t o d i f f e r e n t membranes, such as polymethylmethacry la te , p o l y a c r y l o n i t r i l e (PAN), and e t h y l e n e v i n y l a l c o h o l caused t h e same r e s u l t s . Coagula t ion parameters were w i t h i n normal range . However, p l a t e l e t a g g r e g a t i o n s t u d i e s r e v e a l e d enhanced p l a t e l e t a g g r e g a t i o n induced by ADP and d i s s o l v e d PAN membrane i n DMSO. P r e i n c u b a t i o n w i t h FUT-175 suppressed t h e s e enhanced p l a t e l e t a g g r e g a t i o n t o h i g h e r degree i n t h e p a t i e n t s than i n h e a l t h y c o n t r o l s . Drip i n f u s i o n of FUT-l75(40mg/hr.) a l s o prevented t h e r e d u c t i o n o f p l a t e l e t and t h e e x t r a c o r p o r e a l thrombosis d u r i n g hemodia lys i s .

From t h e s e r e s u l t s , w e conclude t h a t FUT-175 i s an e f f e c t i v e a n t i c o a g u l a n t t o prevent hemodialysis- induced thrombocytopenia . Sumiko Hormna, S h i n j i Asakura, Yasushi Asano, Shigeharu Terukina , Kadoaki Moroi. Dpt. of Nephrology&Biochemistry and I n s t . of Hematology, J i c h i Medical School , Tochig i , Japan.

Artificial Organs, Vol. 13, No . 4 , 1989


101 A NEW APPROACH FOR THE FILTRATE REGENERATION SYSTEM IN THE WEARABLE ARTIFICIAL KIDNEY

In flltrate regeneration system wlth the lmmoblllzed urease. ammonlum Ion decomposed from urea 1s removed competltlvely by the Ion-exchangers from co-exlstlng catlons. Slnce dlvalent catlons such as Ca2+ and Mg2+ are favourably exchanged than NH++. this system needs the supplementatlon of these catlons and thus an addltlonal amount of l o n - exchangers. To mlnlmlze these requlrements, we utillzed the catlonlcallY charged membrane(Asah1 Kasei:A-221.A-201 and A-211) to process cation-free filtrate in whlch urea Is dlalyzed. Three klnds of Ion-exchange membranes were tested In vltro at varying thlckness (0.12 - 0.48 m m ) and charged denslty ( 0 . 9 - 1.6 mEq/g) to evaluate overall mass transfer coefflclents for urea and catlons. In addltlon ex vlvo experlment wlth the mongrel dog (B.W. l8Kg) were carrled out to assess feaslblllty of thls system Using the most sultable membrane selected from In vltro test. Overall mass transfer coefflclent for urea was

0 . 1 6 8 . 0 .062 and 0.063 ml/h/cm2 for A-221, A-201 and A-211. respectively whlle 0.021, 0.003 and 0.034ml/h/cm2 for Ca'+. Under phlsiologlcal Ionic condltlon, required amount of catlon exchanger was reduced to one half - one third even If no supplementatlon of catIon5 was done. Durlng 6 hrs Perfuslon in ex vlvo experlment BUN was malnteined the same level or UP to 23% less value than the Inltial value of each Perfuslon when 109 of urea removal was setted under the simulatlon model based on the In vltro data. There was no need fo r intravenous supplementatlon of dlvalent catlons.

The new flltrate-reseneratlon system needs less than one half to one third of Ion echanger amount, and thus It Is hlshly promisslng to reduce the total welght of the wearable or portable artiflclal kldny.

T.Horluchl, Y.Ohta. Y.Tada. T.Dohl Fac. of Eng.. The Unlv. of Tokyo, Tokyo, Japan

103 A N E W APPLICATION OF CARDIOPULMONARY BYPASS ( C P B ) TO LIVER TRANSPLANTATION (LTx) : IN-SITU L I V E R

TAKEN FROM NON-HEART-BEATING DONORS ( N H B D ) . OXYGENATION ( L O X ) FOR THE SALVAGE OF LIVERS

This study was designed t o evaluate the possi- b i l i t y of successful LTx from NHBD by i n - s i t u LOX using CPB. 24 donor pigs (16-20 k g ) were divided in to s ix groups. The donor pigs were subjected t o card iac a r r e s t ( C A ) f i r s t , t h e n , hepatectomy, by core cooling technique ( C C T ) o r f l u sh technique ( F T ) , was i n i t i a t e d a t e i t h e r 0 min(imnediately), 10 min, or 30 min following C A . In FT, the l i v e r s were cooled with a l a rge amount of cold so lu t ion which was not oxygenated. In CCT with C P B , t he donor pigs were perfused with oxygenated blood a t 35'C f o r 20 m i n , then, the whole body was cooled on CPB t o a r ec t a l temperature of 15'C. I n a l l groups, the donor l i v e r s were then harvested and cold-stored in Euro-Collins' so lu t ion f o r 5 hrs, and transplanted t o r ec ip i en t s using a standard or thotopic technique. Results a r e as follows.

EC Survival EC Survival CA O m in .49 2.06 5/5 .69 k.06 *5/5 CA 10 min .23 k.04 0/4 .47 k.05 * 5 / 5 * CA 30 min .18 5.10 0/2 .26 5.06 0/3

EC : l i v e r t i s s u e energy charge a t harvest Survival : more than 4 days following LTx

FT (witout L O X ) CCT ( w i d 1 L O X )

In -s i tu l i v e r oxygenation with CPB appears t o be e f f ec t ive on the recovery of l i v e r EC ( i . e . v ia - b i l i t y ) a f t e r r e l a t i v e l y short periods of C A , and could well make i t possible t o u t i l i z e l i v e r s taken from NHBD. Takanobu Hoshino, Isamu Koyama, Yasushi Taguchi, Manabu Kazui, and Ryozo Omoto. From the F i r s t Department of Surgery, Saitama Medical School, Saitama, Japan.

The resu!ts of nu t r i t i oca l treatment wit!: :he ars i f :c ia i gapcreas during intravenous hyper- ai:nentationiIVii are reported. ;MATERIALS AN3 MEPYODS! The :nstrumen?s used were STG-i1A and SPG-22. made by Nikiiiso Co. Thirty- fcur pat ienrs , who received the treatment for a t o i a l of 189 days were selected. Deviation of j l o o d giucose and influence of infection on glucose Loierance were stcc:ec. :SZSUiTS: !)The mean biood glucose was maintained w i t h an ideal racge, a t 188+31mg/dl during iVB. This was accomplished. although mst of then: had a high energy uptake. A d i f ference between t h e mean blood glucose and the goai , and a mzximum daily difference were a l so studied t o evaluate the effect iveness of the biood glucose control . B o t h parameters were good in 58%. Neither of them were good i n 13%. 2)The energy intake per insul in r a t i o (E/I ra t io: kcal /uni t ) was studied t o evaluate :he degree of glucose toierance. This r a t i o was 31.6 on the average. Twenty-eight percent belonged t o the group of lowest raLio of less than 15. The group with severe degree of infect ion had a lower E / I r a t i o of 26 .2 i17 .5 . [CONCL!!SION] The a r t i f i c i a l pancreas was useful i n controling b lood glucose o f severely i l l pat ients . iiowever, there were some d i f f i c u l t i e s , when pat ients had severe infect ion.

Masami Hoshino, Yoshikura Haraguchi and Manabu K i r i t a Dep of !CU, Tokyo Police Hospi ta l , Tokyo, Japan

104 VANADIUM TRANSFER DURING HEMODIALYSIS

Vanadium (V) i s an essent ia l trace elements for human nutrition. Massive accumulation of V causes many sor ts of diseases such as hypertension, cardiovascular disease, anemia, neuropathy and bone diseases. Serum V levels i n chronic hemodialysis (HD) patients are high and cause many kinds of complication of patients undergoing HD. Transport of V i n 100 chronic HE patients during HE were examined. V levels in tapwater, deionised water purified water and final dialysate were 18t4 ng/ml, 221 n g / d , 0.1 ng/ml and 0.4-+0.2 ng/ml. Serum V levels and u l t r a f i l t r a b l e V levels in serum (non- protein binding V l eve ls ) were 19.4k8.6 ng/ml and 1.30.2 ng/ml. Serum V a t the inflow s i t e and outflow s i t e were 19.4k8.6 ng/ml and 13.4k4.9 ng/+. Dialysate V levels a t inflow site and outflow s i t e were 0.4iO.2, l.li0.6 ng/ml. V transfered from blood t o dialysate through the membrane. Serum V V levels in 100 HD pat ients s ignif icant ly decreased from 19.4i8.6 ng/ml before d ia lys i s t o 13.8k5.7 ng / m l . Significant re la t ionship between serum V levels and serum Al levels , serum S i , serum @-a, serum Ca, serum Pi, RBC, H b , Hct, serum renin, serum aldosteron and systor ic blood pressure values were found i n 100 HD patients.

In conclusion, V moved from blood t o dialysate due t o diffusion during HD because f r e e diffusible V levels i n serum were higher than V levels in dialysate. I t is necessary t o use low V levels dialysate with HC f o r removal of V.

S. Hosokawa, A. Oyamaguchi, 0. Yoshida' Utano National Hospital, Kyoto, Japan Kyoto University Hospital, Kyoto, Japan*

Artificial Organs, Val. 13. NO, 4, 1989


105 CLINICAL ASSESMENT OF IYMUNOADSORPTION UNDER MEMBRANE PLASMAPHXRESIS T?&ATMENT FOR MYASTHENIA GRAVE (MG)

Seven patients ( 4 female, 3 male average age: 43.6 years) with MG were treated with immunoadsorption under membrane plasmapheresis (IAE') . Immunoad- sorption column (ASAHI, Med. Co) was made with tryptophan. Plasouto 1000 (ASAHI, Med. Co) as a mschine, the plasma separator as a first filter (ASAHI Med Co) and immunoadsorption column were used for plasma perfusion. IAP treatment was performed 3 times per week until t o t a l 6 times of IAF therapy were performed, and after that, IAF therapy was done every three weeks. Blood flow was 60 ml/min and plasma flow was 20 ml/min. The plasma volume of perfusion was 2.5 liters in each IAP therapy. Anti-acetylcoline-antibody values significantly decreased from 76.4k24.4 to 42.6216.1 nmol/l after IAP treatment. IgA, IgM and IgG levels improved 7 of 7 patients after IAP therapy. Loss of total protein and albumin was not found during IAF therapy. Activities of helper T cells and of natural killer (NK) cell significantly (p<O.Ol 1 increased post IAP therapy. Muscle power improved 4 of 7 patients. Eye ptosis improved 5 of 7 patients. Walking improved in 3 Of 7 patients. Visual disturbance improved 4 of 7 patients. None of 7 patients was not found any side effects by IAP treatment.

fcr MG. IAF therapy will be able to clinically useful use for MG treatment.

In conclusion, IAP treatment was very effective

Shinichi H o s o k s , Atsushi Oyamaguchi, Ommu Yoshida'c Utano national Hospital, K,f,to University HospitalQ, Kyoto, JAPAN

107 CHANGING PATENT POPULATION, RESULTS AND PROBLEMS IN CHRONIC HEMODIALYSIS

Patients accepted to chronic hemodialysis have changed dramatically. To be able to predict the need for chronic dialysis and support services we carefully analyzed these changes and survival, and cause of death during 23 years.

Between 1965 and 1987 274 patients were accepted. 60 are alive on dialysis, 74 died, 113 were transplanted and 27 sent to other units. Comparing patients accepted before 1980 to those after the mean age increased from 45 to 54 years (p=OOOl) the creatinine level at acceptance decreased from 1152 to 965 pmol/l (p=O.OOl). The mastolic pressure decreased from 94 to 91 mm Hg. (p=0.007) and the number of co-morbid conditions increased from 1.3 to 1.4 (p<0.005) The diagnostic pattern changed from over 90% primary renal disease to 20% systemic diseases such as nephrosclerosis and diabetes (p=0.04). The chance of receiving a renal transplant decreased from 46 to 39% (p=0.28). In both time periods were the transplanted patients younger than the dialyzed 42 vs 47 years (p=0.03) before 1980 and 49 vs 56 (p=O.OOOl) after. The patients who were nansplanted had fewer co-morbid conditions, but this was not statistically significant. The death pattern changed and in particular withdrawal from dialysis increased from only 2 of 40 deaths before and 8 of 34 after 1980 (p=0.047). The mortality rate was reduced to only 1/4 to that before, in all age groups.

The patient population on dialysis is aging, have more c,ther diseases, is started earier on dialysis and survives h g e r . This is changing the demand for supervision of dialysis and is increasing the demand for back-up hospital t'eds and societal social services.

Hritta. Hvlander Helene Lundblad, Carl-M Kjellstrand Thvision of iephrology, Department of Medicine Ehrolinska Hospital and Institute, Stockholm. Sweden

lo6 PERCUTANEOUS CARDIAC ASSIST USING HELIFOIL IMPELLER

Clinical application of pencil-size, percutaneous blood pumps in cardiac assist has been limited due primarily to the high speed revolution necessary for removing sufficient amount of blood from the venmcular chamber for systemic circulation.

A unique mechanism has been developed by using a helical-shaped foil impeller within a cylindrical housing. Utilizing the aerodynamic lift force generated by the foil, thrust is produced to energize fluid motion. This mechanism significantly increased the efficiency of transforming the mechanical energy to flow energy. The impeller is designed to provide maximum flow area within the 6mm LD. housing. It resulted in a small size, low shear rate, percutaneous blood pump. The rotational speed of the impeller is reduced accordingly, by a meaningful margin, compared with the conventional axial pump design.

In addition, the aerodynamic efficiency produces smooth flow pathlines which virtually devoid of adverse pressure gradient along t h e pathlines. The relatively small energy loss due to boundary shear stress (skin friction) can be further reduced by surface treatments such as hydromer coatings.

Ned H. C. Hwang and David P. Summers Cardiovascular Flow Dynamics Laboratory, University of Houston, Houston, Texas 77204, USA

108 ANASTOMOTIC INTIMAL HYPERPLASIA ON FEMORO-POPLITEAL ARTERY BYPASS GRAFTS.

Sixty-six fernoro-popliteal arterial bypass graftings were made with three different kinds of vascular graft, namely, twenty-four of in-situ autosaphenous vein (V), 20 of expanded polytetrafluoroethylene (EPTFE), an6 22 of Sauvage EXS knitted Dacron (k-D) grafts . rates, at the sixtieth month of V and k-D were 71.0% and 86.1%, respectively, that of EPTFE was Only 30.8%.

Twenty grafts ( 5 grafts of V, 12 of EPTFE, and 3 of k-D) were obstructed because of intimal hyperplasia at the anastomosis (11 grafts) and progression of the distal disease 1 9 ) . Six out of 11 grafts which were obstructed due to anastornotic hyperplasia were EPTFE grafts,

V and k-D were recognized the preferable materials for fernoro-popliteal artery bypass grafting because of the smooth lining of the pseudointima at the anastomosis and, therefore, of the excellent long-term patency rate.

However, the curnrnulative patency

IJIMA, H., MURAI, T., SAKAKIBARA, Y., TSUTUI, T., MITSUI, T. and HORI, M.

*DEPARTMENT OF SURGERY, INSTITUTE OF -CLINICAL MEDICINE, UNIVERSITY OF -TSUKUBA, TSUKURA 305

Artificial Organs, Vol. 13, N o . 4, 1989


109

111

PERFECT REMOVAL OF H I V FROM INTERMEDIATE CON- CENTRATE OF FACTOR VIII PREPARATION (RCG-5) USING BMM MEMBRANE FILTRATION

(RCG-5) developed i n t h e Japanese Red C r o s s is prepared from well-screened and s m a l l pooled plasma, and consequent ly have l i t t l e r i s k of H I V i n f e c t i o n . I n t h i s s t u d y , i n o r d e r t o f u r t h e r i m - prove t h e s a f e t y of FVII I p r e p a r a t i o n concern ing t h e v i r a l i n f e c t i o n such as HIV, an a p p l i c a t i o n of BMM (Bemberg Micro-porous Membrane) f i l t r a t i o n f o r t h e p e r f e c t removal of H I V was i n v e s t i g a t e d .

The BMM hollow f i b e r modules (mean pore s i z e i s from 70 t o 100nm, and membrane a r e a is from 0.003 t o 0.03 in2) were used. H I V was c u l t i v a t e d from MT-4 ce l l l i n e and 20 ml of RCG-5 (VII1:C 12 .5uni t /ml) o r t h a t c o n t a i n i n g H I V w a s f i l t e r e d through BMM, and t h e f i l t r a t i o n r a t e s and pres- s u r e s of module i n l e t ( P B i ) were measured. F a c t o r V I I 1 : C and H I V c o n c e n t r a t i o n of bulk s o l u t i o n and f i l t r a t e were determined.

With BMM of over 0.01m2 of membrane a r e a , 20 m l of RCG-5 was r a p i d l y and e a s i l y f i l t e r e d w i t h i n 10 min, with no i n c r e a s e of PBi. Recovery of V 1 I I : C was over 0.9. The plaque assay i n d i c a t e d t h a t t h e l o g a r i t h m i c r e j e c t i o n c o e f f i c i e n t of H I V was over 4.8 and t h e f i l t r a t e h a s no i n f e c t i v i t y .

f o r t h e p e r f e c t removal of H I V from t h e FVIII p r e p a r a t i o n of RCG-5. Hiro u k i I k e d a l ) Tsugikazu Tomonol), Yoshiaki HamaLoto , Kazuio Yarnaguchi2) Naoki Yamamoto2) Takashi ;k -umi3) Gen I s h i k a w a l ) , Masuo S a t a n i 3 ) and Sadayosi S e k i g u c h i l ) 1 )Japanese Red Cross Plasma F r a c t i o n a t i o n C e n t e r , Tokyo, Japan 2)Yamaguchi Univ. School of Medicine, Yamaguchi, Japan 3)Asahi Chemical I n - d u s t r y Co. L t d . , Tokyo, Japan

I n t e r m e d i a t e c o n c e n t r a t e of FVIII p r e p a r a t i o n

I n conclus ion , BMM f i l t r a t i o n method is u s e f u l l

DEVELOPXENT AND EVALUATION OF J E L L Y F I S H VALVE FOR ARTIFICIAL H E A R T ( A H ) BLOOD PUMP

lems such a s a n t i t h r o m b o g e n i c i t y , d u r a b i l i t y and c o s t , e t c . The development of a valve made of medical polymer h a s been expected s i n c e t h e begin- n i n g of AH s t u d y w i t h o u t s u c c e s s . We developed a new v a l v e f o r AH named j e l l y f i s h ( J F ) v a l v e under a new concept . JF v a l v e h a s a very s imple s t r u c t u r e i n which a t h i n polymer membrane is f i x e d i t s cen- t e r on a v a l v e s e a t . S o , it h a s n o t a c e n t r a l flow b u t an a n u l a r f l o w . A v a l v e s e a t and a f l e x - i b l e membrane with 20 mm d iameter were made of s o l u t i o n c a s t e d polyure thane and Card io thane , r e - s p e c t i v e l y . The v a l v e s e a t had 1 2 spokes t o s t a y t h e membrane and was coa ted wi th Card io thane . The c e n t e r o f t h e membrane wi th ZOO urn t h i c k w a s adhered wi th Cardiothane on t h e va lve s e a t . The va lve w a s i n s e r t e d i n t o t h e i n l e t and o u t l e t p o r t s of t h e blood pump and adhered seamless ly .

r e s i s t a n c e o f JF v a l v e w a s t h e same w i t h Bjork- Shiley(B-S) v a l v e , and t h e r e g u r g i t a t i o n charac- t e r i s t i c s o f J F v a l v e was s u p e r i o r t o B-S v a l v e . No s t a g n a t i o n p o i n t w a s observed around t h e membrane. The blood pump was used t o a g o a t f o r 113 days as t o t a l r i g h t h e a r t bypass wi thout an t icoag- u l a n t . The plasma free hemoglobin l e v e l w a s less than 2 mg/dl. The v a l v e d u r a b i l i t y t e s t i s g o i n g on o v e r 6 months wi thout f a i l u r e a t t h e c o n d i t i o n of 6 L/min o f o u t p u t , 210/160 mmHg of o u t l e t p res - s u r e and 100 bpm of p u l s e r a t e i n a mock c i r c u l a - t o r y system.

K. Imachi , K . Mabuchi, T. Chinze i , Y . Abe, K.Maeda I<. I m a n i s h i , T. Yonezawa, M . Suzukawa, I . Fuj imasa and K. Atsumi I n s t . of Med. E l e c t r . , Facul ty of Med., Univ. o f - Toyko, Tokyo, Japan

The va lve for AH h a s s t i l l s e v e r a l s e v e r e prob-

The f o l l o w i n g r e s u l t s were obta ined . The f low

T h e JF v a l v e is promiss ing t o use f o r AH.

110

112

N E E D L E TYPE GLUCOSE SENSORS BASED ON Ti02 TYPE OXYGEN ELECTRODES WITH A N E W CONCEPT

A new needle type g lucose s e n s o r f o r the a r t i - f i c i a l pancreas has been developed us ing a new t y p e oxygen e l e c t r o d e system (OES) based on a new concept . A t i t a n i u m wire ca thode of 0 .5 mm i n d i a . was hea t s e a l e d w i t h i n a g l a s s c a p i l l a r y , and t h e y were surrounded by a t u b u l a r Ag anode. A t o p o f the e l e c t r o d e was pol i shed w i t h an a b r a s i v e paper. and a n o d i c a l l y oxid ized t o make a T i 0 2 l a y e r w i t h an appl ied p o t e n t i a l of 20 V f o r 0.1 coulomb i n a dil-HaS04 s o l u t i o n . Glucose oxidase was immobi- l i z e d on the s u r f a c e o f the Ti e l e c t r o d e t r e a t e d wi th 3-aminopropyltriethoxysilane using g l u t a r - a ldehyde and bovine serum albumine. I n o r d e r t o i n c r e a s e t he upper response l i m i t of t h e g lucose l e v e l (GL) of t h e sensor , c e l l u l o s e a c e t a t e (CDA) l a y e r s were made on t h e s u r f a c e of t h e s e n s o r by a d ipping method. S t a t i o n a r y r e d u c t i o n c u r r e n t s of oxygen have been observed between -0.7 t o -0.9 V v s . Ag/AgCl/sat 'd K C 1 , t h e r e f o r e , we adapted -0.8 V as the apply ing p o t e n t i a l f o r t h e OES and t h e g lucose s e n s o r s . The OES responded l i n e a r l y up t o 21% Po2 and t h e r e s i d u a l c u r r e n t was enough small . T h e g lucose s e n s o r covered w i t h a few l a y e r s o f CDA membranes responded l i n e a r l y up t o 700 mg/dl of G L under 21 % Po2. In t h e IVGTT, the g lucose s e n s o r i n s e r t e d i n t h e subcutaneous tissue of a normal dog showed an apparent response t o twice i n j e c t i o n s of g lucose ( 4 g each) .

S h o i c h i r o Ikeda, Kaname I t o , Kunitoshi Ohkura". Katsuki Ito". Hiroshi Takagi*. Tatsuhei Kondo"

Dept. of Appl. Chem., Nagoya I n s t . o f Technology, Nagoya, Japan , ++ The 2nd Dept. of Surgery, Nagoya U n i v e r s i t y . School o f Medicine, Nagoya, Japan.

MECHANICAL CIRCULATORY ASSISTANCE BY MEANS OF LEFT HEART BYPASS WITH BIO-PUMP

(LHB) was s t u d i e d e x p e r i m e n t a l l y and c l i n i c a l l y . Acute myocard ia l i n f a r c t i o n ( M I ) w i t h c a r d i o g e n i c shock w a s produced by m u l t i p l e l i g a t i o n of t h e l e f t coronary a r t e r y i n dogs. A l l of t h e dogs i n which any s u p p o r t i v e procedures w e r e no t a p p l i e d d i e d of p r o g r e s s i v e h e a r t f a i l u r e w i t h i n 90 minutes . I n 16 dogs , LHB w a s i n i t i a t e d immediately a f t e r c a r d i o g e n i c shock due t o AMI. These dogs t r e a t e d by LHB were d i v i d e d i n t o 2 groups accord- i n g t o t h e ra te of bypass f low. Bypass f low was c o n t r o l l e d a t one h a l f of t h e c a r d i a c o u t p u t o b t a i n e d j u s t b e f o r e t h e bypass w a s s t a r t e d i n group I and bypass f low w a s f u l l y performed a t any t i m e i n group 11. I n c r e a s e i n Aop (mean) by 14% was observed i n group I, and by 26% i n group 11. Decrease i n LV max.dp/dt by 13% w a s recognized i n group I and by 48% i n group 11, 1 hour a f t e r i n i t i a t i o n of LHB.

C l i n i c a l l y , LHB w i t h Bio-Pump w a s employed i n 4 p a t i e n t s w i t h t h e aneurysms of descending t h o r a c i c a o r t a o r thoraco-abdominal a o r t a . The proximal cannula w a s in t roduced i n t o t h e l e f t a t r i u m through t h e l e f t a t r i a l appendage and d i s t a l cannula w a s l o c a t e d i n t h e l e f t femora l a r t e r y . Mean a r te r ia l p r e s s u r e s between 70 and llOmmHg i n t h e upper e x t r e m i t y and 60 and l l W g i n t h e lower e x t r e m i t y were main ta ined by c o n t r o l l i n g t h e bypass f low rate between 0.8 and 1 . 7 L/min. d u r i n g LHB. There were no abnormal f i n d i n g s about b lood ce l l s , r e n a l , h e p a t i c f u n c t i o n and pos t - o p e r a t i v e c o u r s e . Masanao I m a i , Masayoshi Okada, Maki Kubota, Kazuo Nakamura Department o f Surgery , D i v i s i o n 2, Kobe U n i v e r s i t y School of Medicine, Kobe, Japan

Usefu lness of Bio-Pump f o r l e f t h e a r t bypass



113

115

TETRAfLUOROETHYLENE/PERFLUOROALKYL VINYL ETHER COPOLYMER AS A CANDIDATE MATERIAL FOR VASCULAR PROSTHESES Po 1 y ( e thy 1 en e te reph th a1 at e ) (PET ) and po 1 y -

tetrafluoroethylene(PTFE) have been exclusively heen used as materials for vascular prostheses. In this paper, I would like to report feasibility of tetrafluoroethylene/perfluoroalkyl vinyl ether c:opolymer(PFA), which has the properties similar to PTFE as perfluoropolymer. PFA, PET and PTFE films were evaluated and

compared for their biological properties by in vitro cell culture experiment and by animal implantation test. Ca.9.22 epithelial cells were incubated on the

films and cell attachment and growth were neasured. Low initial cell attachment and high growth rate was observed in PFA, while PET showed hi.gh initial cell attachment and ETFE showed high growth rate. The films were implanted subcutaneously in rats

for upto 2 4 months. PFA produced the thinnest fibrous tissue capsule around the film, while PET formed the thickest capsule and PTFE gave medium one. Thin capsule formation would be a desirable feature for vascular prostheses to control the thickness of pseudoneointima. PFA is worth applying to vascular prostheses,

because PFA is thermoplastic, has various advantage over PTFE in processability, and PFA filament, fiber and fabric are commercially available now.

Yohji Imai Inst. Medical L Dental Engineering, Tokyo Medical 1; Dental University, Tokyo, Japan

EVALUATION OF DIALYSATE CALCIUM AND MAGNESIUM CONCENTRATIONS USING A PLATEAU VALUE

The optimum concentrations of dialysate calcium and magnesium are still obscure. We therefore studied the concentrations of dialysate calcium and magnesium using a plateau value.

l’lasma calcium and magnesium changes during a hemodialysis with three different calcium and magnesium concentrations of dialysate were studied in 43 patients with chronic renal failure. The plateau values of plasma calcium and magnesium during a single hemodialysis were caluculated by the regression line between the pre-dialysis values of plasma calcium and magnesium, and the changes of plasma calcium and magnesium levels during the dialysis. In the three different calcium concentrations of dialysate, 3.5, 3.0 and Z!.5 m E q / l , each plateau value of plasma calcium was 5 . 2 , 4.9 and 4.3 mEq/l. In the three different magnesium concentrations of dialysate, 1.5, 1.0 and 0.5 mEq/l, each plateau value of plasma magnesium was 2.4, 1.7 and 1.4 mEq/l.

In conclusion, the plateau values of plasma calcium and magnesium were different with different calcium and magnesium concentrations of dialysate. The plateau value is therefore useful f o r the clinical studies of the optimum concentrations of dialysate calcium and magnesium.

-_ O:.hi Inagaki, Tadayasu Syono, Yoshihiko Nishian Hidetaro Mori, Seishi Inoue, Yoshikazu Fujita 1)ialysis Unit, Hyogo College of Medicine Xshinomiya , Japan

114 THE EFFECTIVENESS OF LEFT VENTRICULAR ASSIST DEVICE ON MYOCARDIAL BLOOD FLOW AND PO2 IN THE ISCHEMIC HEART

The purpose of this study is to evaluate the effectiveness of left ventricular assist device (LVAD) on the ischemic myocardium.We investigated myocardial oxygen supply demand relationship, regional myocardial blood flow and PO2 in the ischemic heart during LVAD.

Material and Methods:LVAD were implanted in six goat (25-40kg) under halothane anesthesia.Ischemic heart was produced by left anterior descending artery(LAD) ligation. We measured regional myocardial blood flow (MBF),and myocardial PO2 (M PO21 in the ischemic myocardium.And tension time index (TTI) and DPTI/TTI were calculated. These data were studied before(B) and 1 hour(lH), 3 hours(3H) after LAD ligation.

38?23( lH),35?5(3H) and 54?14,3691,39?4 without LVAD.Before LAD ligatiotP,MBF during LVAD was decreased.AfterLAD ligation,MBF decreased and there was no difference between MBF with and without LVAD.MP02(mHg) with LVAD-2890(B),19i16(1 H),15i13(3H) was not significantly higher than without LVAD-23+12,15i14,15?1O.TTI with LVAD was lower than without LVAD. DPTI/TTI with LVAD was higher than without LVAD,especially after LAD ligation. This suggests LVAD increased myocardial oxygen supply demand ratio in the ischemic heart.

demand relationship in the ischemic heart,did not significantly increased myocardial blood flow and PO2 in the ischemic myocardium. LVAD was not effective on improvement of the regional coronary circulation in the ischemic myocardium.

Results:MBF(ml/min/lOOg) with LVAD was 66?10(B),

Conc1usion:Although LVAD improved oxygen supply

Kiyotaka Imoto,Jiro Kondo,Hirokazu Kajiwara,Satoru Sakamoto,Ichiya Yamazaki,Akihiko Matsumoto 1st Depertment of Surgery, School of Medicine, Yokilhama City University, Yokohama, Japan

116 DIGOXIN-LIKE IMMUNOREACTIVE SUBSTANCES (DLIS) IN HEMODIALYSIS PATIENTS

Recently, many researchers have reported that digoxin-like immunoreactive substances (DLIS) are detected in patients with renal failure or others who have never received digoxin. We investigated the detection rate of DLIS in chronic renal failure using fluorescence polarization immunoassay method (TDx Digoxin 11; Dainabot Laboratories).

As a result, DLIS in excess of 0.4 ng/ml was found in five out of 50 hemodialysis (HD) patients. The concentration of DLIS was scarcely decreased by HD in these patients. Four out of the five patients had hepatic dysfunction (case 1: cirrhosis+ hepatoma; case 2 : cirrhosis; case 3: acute liver damage; case 4 : drug induced hepatitis ). Case 1,2 and 3 died within a month after DLIS was detected. Endogenous DLIS is thought to be a prognostic marker,The concentration of DLIS in case 4 was decreased by plasmapheresis, and she is now alive. DLIS was also detected in case 5 with normal hepatic function. On his own, this patient had been taking a herb medicine sold over the counter for about two years. Since DLIS was decreased to under 0.2 ng/ml after stopping the herb medicine, this drug was thought to be the cause of DLIS.

High DLIS (;0.4 ng/ml) was detected in four ( cases 1-4) out of 9 patients with hepatic dysfunction (44%). Therefore, if digoxin is administered to patients with renal failure and hepatic dysfunction, one must be careful of the effect of DLIS on the digoxin concentration.

Yutaka Inagaki, Shigeki Otsu, Izumi Amano Department of Artificial Organs, Chukyo Hospital, Nagoya, Japan.



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119

NEW WEARABLE ARTIFICIAL KIDNEY USING VENO-VENOUS BLOOD ACCESS

Continuous h e m o f i l t r a t i o n (CHF) i s o f t e n used as therapy f o r hernodialysis (HD) p a t i e n t s w i t h h e a r t f a i l u r e o r hypotension. The a u t h o r s have developed a new wearable a r t i f i c i a l k idney u s i n g veno-venous blood a c c e s s . T h i s system c o n s i s t s of f o u r p a r t s : (1) f l e x i b l e double lumen c a t h e t e r wi th dacron c u f f (d-FDL c a t h e t e r $ ; (2) h e m o f i l t e r made of p o l y a c r y l o n i t r a t e (0 .1 m ) ; ( 3 ) s m a l l blood pump ( 7 x 7 ~ 2 0 cm, 1 . 2 k g ) , ( 4 ) c i r c u i t and s a f e t y d e v i c e s . The d-FDL c a t h e t e r w a s i n s e r t e d through t h e s u b c l a v i a n v e i n by S e l d i n g e r s ' method. Dacron cuf f is used t o prevent i n f e c t i o n v i a t h e s k i n . Heparin was cont inuous ly i n j e c t e d i n t o t h e c i r c u i t us ing a micropump (200 9 ) . Two pumps a r e o p e r a t e d by a charg ing b a t t e r y . Hemof i l te r and

pumps w i t h b a t t e r y are p u t i n t o t h e p o c k e t s of t h e v e s t o r t h e s m a l l c a r r y i n g bag, and t h e p a t i e n t s wi th t h e system can walk f r e e l y . S u b s t a n t i a l f l u i d s were adminis te red o r a l l y i n p r i n c i p l e and i n t r a v e n o u s l y a t rest. A f t e r checking t h e p e r f o r - mance and t h e s a f e t y i n exper iments u s i n g mongrel dogs, t h i s system w a s a p p l i e d f o r f i v e HD pa- t i e n t s w i t h h e a r t f a i l u r e . CHF over 24 hours w a s performed i n two out of f i v e p a t i e n t s . Hypoten- s i o n w a s n o t observed i n e i t h e r case.

I n conclus ion , t h r e e advantages w e r e recognized i n t h i s system compared w i t h t h e p r e v i o u s one us ing a r te r io-venous f i s t u r a . 1) The i n f l u e n c e on c i r c u l a t i o n dynamics w a s decreased . 2) P a t i e n t s can u s e b o t h hands f r e e l y . 3) C l o t t i n g of t h e h e m o f i l t e r w a s decreased because of t h e s t a b l e blood f low. Yutaka I n a g a k i , Takashi Miyazaki , Izumi Amano Department of A r t i f i c i a l Organs, Chukyo H o s p i t a l , Nagoya, Japan .

A POSSIBLE BRIDGE SYSTW FOR HE4RT-LUNG TRANS- PLANTATION: A PULSATILE VPHO-ARTERIAL BYPASS m m

A p u l s a t i l e v e n o - a r t e r i a l bypass system (PVAB), c o n s i s t i n g of an a i r - d r i v e n p u s h e r - p l a t e pump and a membrane oxygenator , has been developed t o suppor t c a r d i a c and r e s p i r a t o r y f u n c t i o n . And i t was e v a l u a t e d exper imenta l ly i n comparison wi th a b i v e n t r i c u l a r assist system (BVAS), which had two of t h e same pumps. Twenty-f ive v e n t r i c u l a r f i b r i l l a t e d g o a t s were d i v i d e d i n t o two groups : 15 f o r PVAB and 10 f o r BVAS.

PVAB had f lows of 80.0+11.1 ml/min/kg (base- l i n e ) , 51.355.0 ( 6 h r ) and 64.5516.5 (18 h r ) , and BVAS had t h o s e of 79.724.0, 69.653.7 and 7 4 . 2 ~ 1.0. Mean a o r t i c p r e s s u r e was 101.827.7 mmHg ( b a s e l i n e ) , 5 7 . 8 ~ 6 . 0 ( 6 h r ) and 64.559.9 (18 h r ) i n PVAB, whi le 103.1+4.0, 74.726.8 and 62.028.9 i n BVAS. BVAS had a s i g n i f i c a n t l y h i g h e r f low and mean a o r t i c p r e s s u r e at 6 h r b u t n o t a t 18 h r . Serum f r e e hemoglobin i n c r e a s e d from 2.650.3 mg/dl ( b a s e l i n e ) t o 11.321.6 ( 6 h r ) and 2 3 . 4 ~ 1 . 3 (18 h r ) i n PVAB. PVAB main ta ined a r t e r i a l oxygen s a t u r a t i o n between 96.9 and 100 X though t h e an imals were v e n t i l a t e d twice a minute .

of s u p p o r t i n g c a r d i a c and r e s p i r a t o r y f u n c t i o n f o r a s h o r t term, can be used a s a b r i d g e t o hear t - lung t r a n s p l a n t a t i o n and has a p o s s i b i l i t y t o be developed i n t o a t o t a l a r t i f i c i a l h e a r t - lung system i n t h e f u t u r e .

Hiroyuki Irie, T a i j i Murakami,, Kohzo Ishino,. Yoshimasa Senoo*, Shigeru Teramoto*. S e t s u o T a k a t a n i . ( A r t i f . Organs, Cleveland C l i n i c , C l e v e l a n d , Ohio, U.S.A. *:Dept . of S u r g . , Okayama 'Jniv. Med. Sch . , Okayama, Japan)

These r e s u l t s s u g g e s t t h a t o u r PVAB i s capable

118

120

THE NEW AUSTRIAN I N N E R EAR PROSTHESIS (COCHLEAR IMPLANT) COMBINING ANALOG AND PULSATILE STIMULATION An improved method f o r t h e coding of speech i n f o r - mat ion i n t o a d e q u a t e s i g n a l s f o r t h e s t i m u l h t i o n of t h e a u d i t o r y n e r v e h a s been developed. It com- b i n e s t h e p e r i o d i c i t y p r i n c i p l e , which has been employed up t o now by s i n g l e channel ana log s t i m u - l a t i o n used i n t h e A u s t r i a n c o c h l e a r p r o s t h e s i s , wi th t h e p l a c e p r i n c i p l e by s imul taneous s t imula- t i o n of t h e ana log channel and p u l s a t i l e s i g n a l s on o t h e r c h a n n e l s . The second formant f requency de termines t h e p l a c e of s t i m u l a t i o n f o r t h e pulsa- t i l e s i g n a l s . The 6-channel c o c h l e a r implant implementing t h i s s t r a t e g y i s manufactured as a hybr id c i r c u i t u s i n g 2 ASICS ( a p p l i c a t i o n s p e c i f i c i n t e g r a t e d c i r c u i t s ) b u i l t i n CMOS-technology. I t is encapsula ted i n a h e r m e t i c a l l y s e a l e d ceramic package. Transcutane- o u s s i g n a l - and power- t ransmission is performed v i a an i n d u c t i v e l i n k . Pre l iminary vowel i d e n t i f i c a t i o n tests wi th 6 pa- t i e n t s showed t h a t w i t h p roper t iming of t h e pulses a s i g n i f i c a n t improvement over t h e s i n g l e - channel s t i m u l a t i o n can be achieved .

Ingeborg J . Hochmair-Desoyer, Clemens M . Z i e r h o f e r , Erwin S. Hochmair LSt . f . Angewandte Phys ik - Mikroelek t ronik , Univ. of Innsbruck , A-6020 Innsbruck , Austria

CONTACT ACTIVATION AND BLOOD COMPATIBILITY ASSESSMJZNT

An e x t e n s i o n of t h e parameters u t i l i s e d i n hemo- d i a l y s i s (W) membrane assessment t o i n c l u d e i n f o r m a t i o n on t h e i n f l u e n c e of membranes on c o n t a c t a c t i v a t i o n (CA) would enhance knowledge of blood-membrane i n t e r a c t i o n s . This h o w l e d g e c o u l d promote a b e t t e r u t i l i z a t i o n of HD membranes and t h e development of improved membranes. An i n v i t r o procedure f o r moni tor ing t h e i n i t i a l phase of CA w i t h r e s p e c t t o f a c t o r X I 1 (FXII) a c t i v i t y h a s been a p p l i e d t o t h e f l a t s h e e t membranes Cuprophan and Hemophan (Akzo Ehka AG). FXII a c t i v i t y w a s de te rmined u s i n g a chramogenic s u b s t r a t e . A t room tem e r a Q u r e t y p i c a l r e s u l t s f o r FXII a c t - i v i t y ( U / m l p o b t a i n e d f o l l o w i n g blood-msmbrane c o n t a c t f o r b lood o o n t a l n i n g no a n t i c o a g u l a n t (NAC), h e p a r i n l i u / m l ) , and a low molecular weight h e p a r i n M) (liu/ml) were as f o l l o w s :

CUPROPHAN m i n NAC HEP LMW NAC HEP LM!4H NAC HE€' LMwB 5 .35 .51 .31 .34 .51 -31 -33 - 4 3 -27 10 .34 .48 .29 .36 .49 -70 .34 .42 .26 15 .40 .44 .27 .42 .38 .29 -40 .35 ,25 30 .56 .30 .26 . 75 .31 .27 .54 .28 .23

The procedure f o r d e t e r m i n i n g FXII a c t i v i t y d is - t i n g u i s h e s between c o n t r o l s , a n t i c o a g u l a n t s and membrane s t r u c t u r e , a t v a r i o u s t ime i n t e r v a l s . The r e s u l t s demonst ra te that d a t a can be a c q u i r e d r e l e v a n t t o blood-membrane i n t e r a c t i o n s and t h e CA phase o f blood c o a g u l a t i o n .

Linda I r v i n e , James M.Courtney,Gordon D.O.Lowe B i o e n g i n e e r i n g Wnit,Univ.of Strathclyde,Glaggow UK Univ.Dept. of Med., Royal I n f i r m a r y , Glasgow UK

AEMOPHAN CONTROL I



121 THROMBOPLASTIN COATED POLY- URETHANS: A NEW MODEL FOR "in vivo" BLOOD MATERIAL INVESTIGATIONAL STUDIES Plates (12x22 mm and 0 1-1 thi k) of mented polyurethans weGe coates yith. EEg- man thromboplastln by a method a iba- tion and increase temp rature ? 4 2 O $ for 12 hours in sterife consitions. Subseq en tl the plfteF.wsre prlmed wlth poor 'la- teyet reca ci ie plasma to obtaln a Fi- b in layer,on their surface Immediately

were introduced ln the'descendln :!:%a and in the 1eft.auricle of six Real thy goats. Haematologlcal parameters have been evaluated before and during the imp1 antation. After one week the anlmals have been sacrif-ed for macro and m l roanaly is of the piates.The plates surEaces an8. the aorta and left aurlcle endothella v1 sually examined did not show thrombi'de- positlon ComplAte necro sies were also performe6 for any distane thrombus o r pa-

h o l n u i c a l modiflcation. The imvlanted sa mples-;-re examined by microanalysis tech n ioues Tohotoelectron sDectroscovY, scanner' micG'siopy infrarea spectroscopy reT f Lection? for. ;latelet. adhesion o r protel naceous materlal deposition Preliminar results show ood local thromboresistanT activity of tge coated plates but reat consu tion coagulopath of the l m !?anted animays Further resulTs are on tge way f o r final conclusion.

The main purposes of this work are: - modellin of bioreactor able to p r o -

Tote a nsturaaly turnlng-over flbrln ayer ;

- bi reactor influencing on the haemocoa- guPative system;

- possible using o f this coated membrane as t h r o m b o r e s i s t a n t m a t e r l a l .

UNIVERSITY J.E. PURKYNE. BRNO CZECHOSLOVAKIA. ISABELLA R., Sotolova 0 . . Guba P. and Vasku J.

123 EXPERIMENTAL STUDY OF BIVENTRICULAR BYPASS TAH ---SPECIAL REFERENCE TO REGIONAL RENAL BLOOD FLO-

The purpose of this study is to clarify whether total artificial heart (TAH) can maintain circulations in important organs. Two pusher-plate pumps were used to bypass right and left ventricles in 11 goats and 7 sheep with fibrillating heart. The pumps were driven pneumatically in independent variable rate mode. The organ flow was measured using transit time flow meter and regional blood flow was calculated using hydrogen clearance method. The bypass time ranged from 13 to 24 hours (mean 19.6). Eight 24 hour survivors were sacrificed. The total flow of the control, 12 and 24 hour animal were 73.6, 69.2 and 63.2 ml/min/kg with Sa02 of 98.2, 94.4 and 96.3 %, free plasma Hb of 2.7, 9.9 and 11.3 mg/dl, and lactate level of 15.9, 64.7 and 64.6 mg/dl. The antithrombin-I11 decreased to 52 % of the control. In the 24 hour survivors, the carotid artery flow ratio (flow/ total flow) of the control, 12 and 24 hour animal were 5.3, 5.3 and 5.7 %, the renal artery flow ratio of 5.2, 6.1 and 3.2 %. The regional cortical blood flow/renal(cortex+medulla) blood flow ratio of 41.8, 49.7 and 42.2 %. In the short term survivors, the carotid artery flow ratio of the control and 12 hour animal were 5.1 and 6.8 %, the renal artlery flow ratio of 5.4 and 2.7 %. The regional cortical blood flow ratio of 38.6 and 28.6 %. These data suggest that TAH driven in independent variable rate mode can maintain systemic circula- t i on and peripheral organ perfusion.

_- K(>.zo Ishino, Taiji Murakami, Hiroyuki Irie, Hiroshi Izumoto, Yoshimasa Senoo, Shigeru Teramoto D~partment of Surgery, Okayama University Medical S8:hool, Okayama, Japan

122 ANTIMICROBIAL ACTIVITY OF IODINE IMMOBILIZED FIBER

The polymixin B fibers, tertiary amines and quartarnary ammonium salts were well known as an insoluble antimicrobial materials. However, the antifungal activity was not included. For inventing materials with such activity, the iodine or chlorine bonded with immobilized fiber such as polystyrene fibers was investigated respectively in our experimented studies.

Method: We mainly used candida albicans and sacchromyces cerevisiae that were suspended at the concentration of 1x10' CFU/ml and 1x10' CFU/ml for this study, then put the immobilized antimicrobial fibers dry weight 0.25 g into the fungal suspension 5 ml together to shake for 2 hours and count of colonies since inclubated at sabouraud agar under 25'C 2 days. The change of cell surface was investigated by scanning electron microscope.

Results: Since the results revealed that the both fungi were almost undetectable in iodine group and also without the release of iodine in supernate. Scanning electron microscopic study showed cell surface was damaged. The feasibility of utilizing iodine immobilized fiber as antimicrobial materials, including antifungal activity was substantially comfirmed.

Yutaka Ishii, Thoru Tani, Kenji Numa, Hirohiko Aoki. Toyokazu Yoshioka Yoshihiro Endo and Masashi Kodama First Department of Surgery, Shiga university of Medical Science, Otsu, Shiga. 520-21 Japan

124 HEART VALVE REPLACEMENT WITH ST.JUDE MEDICAL VALVE PROSTHESIS - LONG-TERM CLINICAL RESULTS AND HEMOLYSIS AFTER IMPLANTATION - Between May in 1980 and September in 1988,571 patients received valve replacement with St.Jude Medical (SJM) prosthesis. Their age ranged from one to 73 years (mean,49.3 years). Mitral valve replacement was performed in 377 patients, double valve replacement in 150 (SJM mitral and either BjGrk-Shiley aortic in 99;SJM aortic in 47; o r SJM tricuspid prostheses in 41, aortic valve replacement in 38, tricuspid valve replacement in 4 , and triple valve replacement in 2. Preoperative New York Heart Association (NYHA) class was 76.0% in classes I11 and IV. Early death was in 24 and late death was in 21 patients. Follow up in 372 survivors at more than two years after operation is 89.5% and 97.6% of them are in either in class I or 1I.Twelve patients shows hemolytic anemia and there were no perivalvular leakages in all except two patients. Large amount of blood transfusion, residual aortic regurgitation and liver dysfunction were considered as factors increasing the hemolysis. Severe fetal hemolysis was seen in 6 of them and the prosthesis had been placed in 'anatomical' mitral orientation in four of them. However,after placing the prosthesis in 'anti- anatomical'mitral orientation,we have experienced no fetal hemolysis after implantation. Postopera- tive thromboembolic o r bleeding complications were seen in eight patients.Although much attention should be taken on hemolysis, our clinical experience is promising favorable clinical results after the implantation of SJM prosthesis. Tadashi Isomura,Yoshikatsu Nishi,Koh Tanaka, Kouichi Hisatomi,Akio Hirano,Ken-ichi Kosuga,and Kiroku Ohishi: The Second Department of Surgery, Kurume University School of Medicine


314 ABSTRACTS OF THE Vll th WORLD CONGRESS

125 CHANGES IN INTRACELLULAR Ca2+ CONCENTRATIONS ([Ca2']i) DURING SHEAR-INDUCED PLATELET AGGREGATION(SIPA)

Human Platelets can aggregate in vitro under certain shear stress without any aggregation induccer. To elucidate the mechanism of SIPA, we have investigated the changes in [Caz+]i using Indol/AM as a fluorescent Ca2+-indicator dye. SIPA was measured using cone-plate streaming chamber adapted for continuous recording of light transmisson (M.Fukuyama et al, Thromb. Res. 1989). Washed platelets prepared by the albumin-density gradient technique of Walsh et a1 were incubated with Indol/AM at a concentration of 10 uM for 30 min at 37°C and then were separated by gel filtration on Sepharose 2B. Un- sheared platelets revealed [Caz+]i of 100 uM. When washed platelets were sheared at 108dyne/cm2 in the presence of von Willebrand factor (vWf,lO ug/ml) and 1mM CaClZ, prominent SIPA was observed soon after shearing accompanied by increase in [Ca2+]i to 200 nM. Neither SIPA nor [Caz+]i elevation was observed in the absence of vWf. To further characterize the mechanism of [CaZA Ii elevation, two monoclonal antibodies against vWf were used, LJ-l52B/6 (donation from Dr.Z.Ruggeri, USA) and Avw-3 (donation from Dr.R.Montogomery, USA). The former inhibits vWf binding to platelet membrane glycoprotein IIb/IIIa (GPILb/lTIa) and the latter inhibits vWf binding to GPIb. While both antibodies completely inhibited vWf-mediated SIPA, [Caz+]i elevation was prevented only by Avw-3. Lj-l52B/6 had no effect on [Ca2'li rise during SIPA. These results indicate that binding of vWf to GPIb induced by high shear stress may trigger [Ca2+Ii elevation. I.Itagaki, M.Fukuyama*, K.Kawakami*, K.Sakai*, K.Kawano**, M.Handa** and Y.Ikeda**. Toray Industries Inc., Dept. Chem. Eng. Waseda Lniv.* and School of Med. Keio Univ.**

127 BLOOD-COMPATIBILITY BY GRAFTING WITH ANTI- COAGULANTS

The rwst stdied apFamch to achieve bld-compatibility is "heprinimtion". So far the authors have investigatd the polyurethanes hprinizd bth ionidly ard covalently. GI- sequmtly, we have, in m m c e with other researchers, cam to the conclusion that the hem release was not essential to achieve bldemptibility. In this ppr, two kids of anticoagulant were usd. One of

thm was sdim vinyl sulfate (VS). VS has no anticwgdmt activity, tut polymrizd VS (RS) has the activity. The other was thanbin inhibitor (MD-805, presented by Ntsubiski L e i ) mtaining a vinyl group (W), which was newly synthesized. These ccmpuds wepe gmfbplymerized on the polymeric naterials, which were g lm-d iscb rgd . Tne Wsgrafted naterials de- activated b l c d ooagulation in the presence of antithmbinII1 (ATIII). On the other hand, the plyVMkpfte3 nakrials de- activated it in the absence of ATIII. matelet activatim was m p ~ s s e d on these mterials, as reprtd in earlier pprs on the heprinizd mterials. rnHHCW C H p o€cII-cIII

L =

&oce, VMD ; VS :A

Yoshihiro Ito, Lin Shu Liu, Yukio Imanishi Department of Polymer Chemistry, Kyoto University, Kyoto, 606, JAPAN

126

128

NEW NEONATAL AND PEDIATRIC VENO-ARTERIAL EXTRACORPOREAL OXYGENAT ION (VA-ECMO) CIRCUITS USING AUTOMATICALLY DRIVEN BLOOD PUMPS

VA-ECMO has been successfully used for neonatal respiratory failure, but conventional ECMO circuits using a roller pump are not always free from mechanical complications like venous collapse or air embolism. We developed a new safer circuit using an automatically driven sack type blood pump, which did not produced the negative pressure.

The neonatal circuit primed 65 ml consisted of a 6 ml blood pump with 4 mm ball valves and a membranous lung. The pediatric circuit primed 120 ml had a 10 ml blood pump with 6 mm ball valves. Magnetic-Hall sensors fixed on blood chambers and housings sent electric signals of filling and ejecting blood to the pneumatic power unit which regulated the air pressure quickly and consequently changed the pumping rate and the stroke volume automatically.

Both circuits had been tested on a mock circulation system and in 38 puppies. 85 % of the cardiac output could be bypassed. Bypass flow changed automatically in response to changes in the venous pressure, but remained constant against changes in the arterial pressure. No mechanical problem had been encountered in continuously driving on the mock circulation system f o r 21 days.

We concluded that our circuits are safe and simple s o that they could be handled by a small number of medical stuff.

Takahiro Ito, Takehiko S e o , Hiroyuki Takagi Department of Surgery, Branch Hospital, University of Nagoya, Nagoya, Japan

GLUCOSE-SENSITIVE INSULIN-RELEASING SYSTEM BASED ON REDOX REACTION

The authors desiged ard synthesized a glucose-sensitive insdin-relwing system, using a @!-respnsive memfrrane. However, in the hunrvl tcdy, drastic pxtd because of its hweostasis. In the present ppr, therefore we attanpted to synthesize novel systems tasd on d o x reaction of glucose-sensitive enzymes, as follm. ?he enzyme oxidized g h m s e , ard at the same time, reduced the diSti!Xj.de tcold Linldng the insulin to its qprter. 'hs, in th is &el, the link83 insulin is caused to k released from the supporter. One of the systems is using glucose d-e (GDH) which needs cc-emyms. It was demanstmted that the electron transfer betmen the GDH ard the disulfide tcnd was eJlbancd by cc-hhilization of NAD ard FAD. The other is using glucose oxidase (COD), which does not need co-azyms, cmpld with insulin in a disit?i.de M. ?he resulting tord could be efficimtly cleavage3 by addition of glucose without aqy electron mediators.

changes m t ke ex-

Y. Ito, D.J. Chung, Y. Imanishi Department of Polymer Chemistry, Kyoto University, Kyoto, 606, JAPAN



129 3IOACTIVE MATERIALS ENHANCING CELL ATTACHMENT OR 30LIFERATION

suitable rraterisls to control cell functions is a prc- blem that attracts the attentian of numemus bimter ia l re- searchezs. In the psent pper, we therefore set up to investigate its potential. One is the mterial exhncing cell attachment. ?he other is the mterial enhancing cell gmhh. i)h oder to eslhance cell attachment, celladhesive peptide,

hg-!?Jy-A~spSer (m), w a ~ W b i l i Z d ant0 polymeric IIBIX~- als. Using this peptide ins tad of a cell-adhesive ptein give a compratively large anKnmt of site that was active for cell attachment on the limitfd surface, and moreover the material was more stable against changes in @, heat, and also a,+inst sterilizaticm than mterials imobilizd with the prc+

t 2 i n . cell cell

ii) To increase cell proljfemtion, cell groWn factor was imobilizd on the mterials. Gowth factors ink?raet with cell ii the following way. After biding itself to its receptor, tie growth factor is intemalkd into the target cell by re- c,~ptor+nediaM docytosis. L y s o s d degradation of the re- CqAm-ligard complex accmts for the dw-regulatian of re- c+rs a d self-limiting reqxnse. However, in this research, it was demonstrated that the immbilizd mw+rth factor enhmcd

guhtion. receptor B pmth factor

* Y3shihiro Ito, Shu Qin Liu , Masako Kajihara,and Yukio Imanishi Department of Polymer Chemistry, Kyoto University, Kyoto, 606, JAPAN

131 ENClOSURE O F ISLETS IN A PHOTOCROSSLINKABLE POLY(V1NYL ALCOHOL) FOR A BIOARTIFICIAL PANCREAS

In a bioartificial pancreas islets are im- munoisolated within a semipermeable membrane. Several kinds of materials have been examined to encapsulate islets. Although some of them gave promising results, these were still difficulties in stability and biocornpatibility in vivo. In this study we examined a photocrosslinkable poly(viny1 alcohol) bearing stilbazolium (PVA- SbQ) to enclose islets in a hydrogel tablet. PVA- SbQ used was 500 degree of polymerization and containing 1.5 mol% stilbazolium groups. PVA-SbQ was dissolved in Eagle’s MEM (MEM) in the dark to afford 16.7 wt% solution and autoclaved. Islets were obtained from hamsters by the collagenase digestion technique. Islets were mixed with a PVA-SbQ aqueous solution. The mixture keep fluidity until photo-irradiation. The PVA-SbQ solution was poured into a well with 10 mm in diameter and 2 nun in depth, and then photoir- radiated to proceed crosslinking with a mercury- xenon lamp. Islets were enclosed into a PVA-SbQ hydrogel tablet. They were cultured in MEM supplemented with 5 % serum. They continued to secrete 10 - 20 uU insulin islet-’ day-’ into the culture medium and preserved their round shape and size for >lo0 days. For the evaluation of the :.munoisolation effect of PVA-SbQ, islets from C57BL/6 mice and from hamsters enclosed in PVA- !;hQ tablets were allo- and xenotransplanted into I3ALB/c mice. These results will be also discussed. PVA-SbQ was found to be a promising material for preparation of a bioartificial pancreas in terms of workability and nontoxicity. Hiroo Iwata, Hiroshi Amemiya, Ryosuke Hayashi, Ijhigeki Fujii, Tetsuo Akutsu National Cardiovascular Center, Osaka, Japan

130 24 HR PRESERVATION OF ISOLATED RAT HEARTS PERFUSED WITH STABILIZED HEMOGLOBIN SOLUTION AT LOW TEMPERATURE.

We tried to preserve isolated rat hearts perfused with newly introduced polyoxyethylene- conjugated hemoglobin (stabilized hemoglobin: SHb) solution for 24 hr at low temperature. Isolated rat hearts were perfused with modified Krebs- Henseleit solution at a constant pressure of 80 mmHg at 37 C. Left ventricular systolic pressure(LVSP) was measured using a pressure transducer connected to a latex balloon inserted into the left ventricle. Coronary flow rate(CFR) and ECGs were monitored and pressure-volume relationship was constructed. Thereafter, hearts were perfused with solution containing SHb (3g/dl) at a constant pressure of 13 mmHg at a temperature of 15 C for 24 hr. After 24 hr preservation, re- warmed hearts started to beat spontaneously with slightly decreased rate(85% of control). The LVSP decreased to approximately 60% of the control with a decreased CFR. Results demonstrate that isolated rat hearts can be preserved for 24 hr by SHb solution at a low temperature without showing marked deteriorative effects, and suggest that SHb solution would be usefull as a perfusate for preservation of isolated organs and tissues f o r a long period.

132

Shyuichi Iwasaki, Takashi Yamakawa, Yoshimasa Miyauchi and Katsuhide Nishi. Department of Pharmacology and Surgery, Kumamoto University Medical School, Kumamoto, Japan.

N-ISOPROPYLACRY LAM IDE AND METHACRY LATES COPOLYMERS FOR ENCAPSULATION OF ISLETS

Islets of Langerhans are encapsulated within a semipermeable membrane for the purpose of a bioartificial pancreas. Poly(N- isopropylacrylamide) (polyIPAAm) is a water soluble, temperature sensitive polymer. A s the solution temperature is raised above 33 OC, polyIPAAm precipitates. It exhibits a lower critical solution temperature (LCST) around 33 OC. Random copolymers of IPAAm with 2 - hydroxyethyl methacrylate and n-butyl methacrylate were prepared at selected monomer ratios. The LCSTs of these copolymers covered the range of 0 to 33 OC. The drastic solubility difference below and above the LCST allows the enclosure of islets in precipitated polymers. We focused on the use of polyIPAAm and the copolymers for the encapsulation of islets. Islets were obtained from hamsters by the collagenase digestion technique. 0.2 ml of 9 wt% solutions of each polymers i n Eagle’s MEM (MEM) was mixed with 50 islets at 0 OC. The mixture kept fluidity until it was warmed above LCST. It was poured and cast on a Petri dish, and then raised above LCST by intro- ducing warmed culture medium. Islets were occluded into polymer precipitate. Islets in precipitate were cultured in MEM supplemented with 5% serum. They continued to secrete -10 AIU insulin islet-’ day-’ for >50 days. It demonstrated a good viability of islets in polymers precipitates. Although much remains to be investigated, IPAAm based copolymers are promising materials for preparation of a bioartificial pancreas.

Hiroo Iwata, Hiroshi Amemiya, Tetsuzo Akutsu National Cardiovascular Center, Osaka, Japan

Arfi$cid Organs. Vol. 13, No . 4, 1989


133

135

EVALUATION OF A PYRIDOXALATED HEMOGLOBIN- POLYOXYETHYLENE CONJUGATE AS AN OXYGEN TRANSPORTING PLASMA VOLUME EXPANDER

P y r i d o x a l a t e d hemoglobin po lyoxye thy lene conjug- a t e (PHP) p r e p a r e d from human hemoglobin was examined f o r t h e a b i l i t y t o s u p p o r t t h e v i a b i l i t y of t i - s s u e s by t r a n s p o r t i n g oxygen t o them. Marked r educ - t i o n of ATP c o n t e n t i n r a t l i v e r b rough t a b o u t by a p e r f u s i o n w i t h hydroxye thy l s t a r c h s o l u t i o n w a s r e - s t o r e d by t h e f o l l o w i n g p e r f u s i o n w i t h PHP. Energy c h a r g e , t h e o t h e r i ndex of oxygen s u p p l y t o t i s s u e s , was a l s o w e l l ma in ta ined d u r i n g t h e p e r f u s i o n w i t h PHP ,

T o t a l b lood volume (TBV) and mean a r t e r i a l blood p r e s s u r e (MAP) of r a t were measured i n o r d e r t o a s - s e s s t h e plasma volume expander e f f e c t of PHP so lu- t i o n . TBV d i d n o t change d u r i n g t h e exchange t r a n s - f u s i o n (ET) w i t h PHP f o r 30 min though s l i g h t redu- c t i o n was obse rved a t 2 h r a f t e r i t s t e r m i n a t i o n . MAF remained unchangeable a t 2 h r a f t e r ET a s w e l l a s d u r i n g t h e t r e a t m e n t . On the c o n t r a r y , ET w i t h p y s i o l o g i c s a l i n e caused s i g n i f i c a n t r e d u c t i o n of TBV and MAP. P e r f u s i o n expe r imen t on i s o l a t e d rabb- i t ears was c a r r i e d o u t t o r e i n f o r c e t h e above r e s - u l t s . No change of we igh t of e a r was induced by t h e p e r f u s i o n w i t h PHP i n s p i t e of a s i g n i f i c a n t i n c r e - a s e of e a r we igh t i n t h e s a l i n e group.

Our d a t a i n d i c a t e t h a t PHP i s a b l e t o s u p p o r t t h e v i a b i l i t y of t i s s u e s by d e l i v e r i n g s u f f i c i e n t oxygen t o them and t h a t i t i s endowed w i t h a n a b i l - i t y o f plasma volume expander . PHP would t h e r e f o r e be an e x c e l l e n t s u b s t i t u t e f o r blood i n c l i n i c a l p r a c t i c e .

Se inosuke I w a t a , Kazu tosh i Maeda, Y o s h i t o s h i Kida, Midor i Ban, Yoshimasa Matsuzawa, Y u i c h i Gyotoku L i f e s c i e n c e l a b o l a t o r i e s , C e n t r a l r e s e a c h l a b o r a - t o r i e s , Ajinomoto Co. , I n c . , Yokohama, Japan

POSTOPERATIVE MANAGEMENT USING LEFT VENTRICULAR ASSIST DEVICE FOR VENTRICULAR SEPTAL PERFORATION AFTER ACUTE MYOCARDIAL INFARCTION

Ai r -d r iven l e f t v e n t r i c u l a r a s s i s t d e v i c e s (LV ADS) were a p p l i e d t o f i v e p a t i e n t s w i t h profound l e f t h e a r t f a i l u r e a f t e r s u r g i c a l c l o s u r e of v e n t r i c u l a r s e p t a 1 p e r f o r a t i o n (VSP) f o l l o w i n g a c u t e myoca rd ia l i n f a r c t i o n . An o u t f l o w c a n n u l a was sewn o n t o t h e a scend ing a o r t a and a n i n f l o w c a n n u l a w a s i n s e r t e d i n t o t h e l e f t a t r i u m v i a t h e i n t e r a t r i a l septum from t h e r i g h t a t r i u m t o p r e v e n t a i r suck ing and f o r good d r a i n a g e d u r i n g ca rd iopu lmonary bypass . Four p a t i e n t s were weaned from t h e LVAJI on 1, 3 , 5 and 1 3 p o s t o p e r a t i v e d a y s and t h e f i r s t t h r e e p a t i e n t s d i s c h a r g e d i n good c o n d i t i o n . The f o u r t h p a t i e n t d i e d b e c a u s e of s e p s i s and m u l t i p l e o rgan f a i l u r e on 2 4 t h day a f t e r weaning of LVAD. One p a t i e n t c o u l d not b e weaned from LVAD due t o unexpec ted d i s s e c t i o n of a s c e n d i n g a o r t a . Ca rd iac i n d e c e s were m a i n t a i n e d a t more t h a n 2.5 l/min./u? w i t h LVAD i n t h e s u r v i v a l g r o u p and our c r i t e r i a of t h e weaning from LVAD u s i n g " on-off " method were r e a s o n a b l e a c c o r d i n g t o thei i r e v e n t f r e e c l i n i c a l c o u r s e a f t e r r emova l of LVAD excep t f o r n e c e s s i t y of p ro longed v e n t i l a t i o n s u p p o r t and i n f e c t i o u s c o m p l i c a t i o n i n one c a s e .

LVADs were u s e f u l t o m a i n t a i n t h e o r g a n pe r - f u s i o n a f t e r s u r g i c a l r e p a i r f o r VSP f o l l o w i n g a c u t e m y o c a r d i a l i n f a r c t i o n .

F&Iway_a, Tsuguo I g a r i , Tosh i fumi Abe, K e n i c h i Hag iwara , Masahiro T a n j i , Masaaki Watanabe, S h u n i c h i Hoshino The Department of C a r d i o v a s c u l a r S u r g e r y , Fukushima Medical CoElega,Fukushima, J a p a n

134

136

A TEMPORARY SUPPORT FOR MAKING ANASTOMOSING OF BLOOD VESSELS EASY

There h a s been growing r e q u e s t f o r t h e deve l - opment of a t empora ry s u p p o r t which can b e i n s e r t - ed i n t o b lood v e s s e l s a t the t i m e o f anas tomos ing and b e q u i c k l y d i s s o l v e d away i n the b lood a f t e r s u r g e r y , and d i s s o l v e d elements o f wh ich are qu i - e t l y unha rmfu l t o the o rgan i sm.

p o r t s i n the t u b u l a r form f o r anas tomos ing b lood vessels which comprised of m a t e r i a l s s e l e c t e d from the g roup c o n s i s t i n g o f monosaccha r ide such as D - s o r b i t o l o r x y l o s e , and p o l y s a c c h a r i d e such as h y d r o x y e t h y l s t a r c h o r d e x t r a n . a l s are v e r y h i g h i n s a f e t y when used as a sup- p o r t f o r b lood v e s s e l s .

A t y p i c a l t u b u l a r sample h a s a n o u t e r d i a - meter of a b o u t 4 mm and a n i n n e r d i a m e t e r of a b o u t 2 mm as w e l l a s 10 t o 20 mm o f t h e l e n g t h . In o r d e r t o c o n f i r m that t h e s u p p o r t i s d i s s o l v e d away i n a p r o p e r s h o r t p e r i o d of t i m e ( p r e f e r a b l y i n less t h a n 10 m i n ) , a c i r c u l a t i o n test w a s pe r - formed w i t h v a r i o u s t y p e s o f test f l u i d s such as normal s a l i n e s o l u t i o n , a p h o s p h a t e b u f f e r , and a n a r t i f i c i a l b lood as w e l l as who le blood o f dog a t 37.OoC u n d e r f low rate of 60 t o 200 ml/min by u s i n g a r o l l e r pump sys t em.

I n t h i s s t u d y , we des igned t empora ry sup-

These materi-

Makoto Iwatsuki! Tosh io Hayashi:' Haruo Funaki*** 'Ajinomoto Co. Inc.,"Res. C e n t e r f o r Med. Polym. & Biomat . , Kyoto Univ. >"Na t iona l O j i H o s p i t a l .

EXPERIMENTAL STUDY ON THE PRESSURE SUPPORT FOR THE RIGHT VENTRICLE BY THE LEFT VENTRICULAR BALLOON PUMPING DURING THE LEFT HEART BYPASS.

The effect of the left ventricular balloon pumping (LVBP) in combination with the left heartbypass was

examined, in terms of pressure support for the right heart. Six canine dogs (BW=9.3kg) were used. Heart rate, cardiac output, RV pressure (RVP) , PA pressure (PAP) , and A 0 pressure were measured a s indices. In normal hearts, in injured LV hearts by ligating the distal LAD. and in hearts with injured biventricle by devascularizing the RV free wall following the distal LAD ligation, the changes of the right heart pressures were examined with and without LVBP. In normal hearts, mPAP with LVBP was 22.9k ll.7mmHg. mPAP without LVBP was 20.1+ 5.6mmHg . ( * ) Other pressure indices were not significantly different. In injured LV hearts, sPAP with LVBP was 28.5k4.3mmHg and sPAP without LVBP was 23.7k6.3mmHg. ( * ) indices were not significantly different. In hearts with injured biventricle, pressures with LVBP were significantly raised compared with pressures without LVBP. sRVP rose from 20.9k7.9 nnHg to 31.5k13.9mmHg. ( * * ) mRVP rose from 13.0f 5.5mmHg to 16.2k 6.6mmHg. ( * ) sPAP rose from 22.3f 6.7mmHg to 28.8k 10.PmmHg. ( * ) mPAP rose f rom 15.3k5.2mmHg to 18.8k5.3mmHg . ( * * ) The results indicate that the LVBP, when used in combination with the left heart bypass, can ameliorate the depressed right ventricular function by raising the pressures of the right heart system.

Other pressure

( * ) ; ~(0.05. ( * * ) ; p<0.025

Hiroshi Izumoto, Kozo Ishino. Hiroyuki Irie, Taiji Murakami. Hiromichi Teraoka. Makoto Yamada. Yoshimasa Senoo. Shigeru Teramoto Department of Surgery, Okayama University Medical School Okayama. Japan

ArtiJicial Organs, Vol. 13, No. 4, 1989


137 ENDOTHELIAL CELL SEEDING OF SMALL DIAMETER VASCULAR GRAFTS

Endothelial cell (EC) seeding holds promise of patency for artificial small diameter vascular grafts. Adsorbed fibronectin (FN) has become the most common means of attaching ECs to graft surfaces. This study examines, under flow conditions, the adhesion of ECs to Fh' coated expanded PTFE vascular grafts.

C u l m d ovine carotid artery ECs were labelled with 35S-methionine and inoculated (1.5 x 106 cells/&) onto 3mm internal diameter PTFE grafts which had been precoated with ovine fibronectin. The grafts were seeded with ECs by rolling for 1 hr at 37OC and then either cultured for 48hr or flow tested immediately. Following 48hr incubation ECs had reached confluence. Cell attachment to grafts (n=5) was evahated in an in vitro flow circuit, using flows which were increased stepwise up to 330 ml/mjn. Ex vivo studies (n=5 grafts) were conducted without anticoagulant using autologous cells in a sheep model. The grafts were inserted in an extemalised arterio-venous shunt and exposed to blood flows of -150 ml/min for 3hr.

One hr seeded and 48hr cultured grafts demonstrated >95% cell retention following in vitro flow studies. Ex vivo studies of 48hr grafts also showed EC retention of >95% with no sign of thrombogenicity. Furthermore a preliminary 24hr EX vivo study has shown >95% retention.

This study demonstrates the firm attachment of seeded ECs to FN coated FTFE grafts in the ovine model. The potential loss of seeded ECs in vivo probably would not be related to shear stress alone.

N.J. James, P. Slowiacxk, K. Schindhe1m.B.K. Milthorpe, N.P. Dudman, G. Johnson, J. Steele University of New South Wales, CSlRO Division of Biotechnology,. AUSTRALIA.

139 f i BLOOD PUMP WITH SWINGING ATRIOVENTRICULAR SEPTAL WALL

We have developed a new type blood pump which has a swinging a t r i o v e n t r i c u l a r s e p t a l wal l . The pump c o n s i s t s of a s e m i c i r c u l a r housing having only a s t a t i o n a r y o u t l e t v a l v e , a swinging s e p t a l w a l l having a n i n l e t v a l v e , and a d r i v e s h a f t connected w i t h an end of t h e s e p t a l w a l l . The d r i v e s h a f t i s d i r e c t l y connected w i t h a low-speed IK motor. I n o t h e r words, t h e pump d r i v i n g system has no motion convers ion mechanism. Because of i t s s i m p l i c i t y , i t i s expected t o be e x c e l l e n c e i n d u r a b i l i t y . The maximum s t r o k e volume of the pump is about 70 mL. The swinging s e p t a l w a l l d i v i d e s the blood pump i n t o a n a t r i a l chamber and a v e n t r i c u l a r chamber. Two S t . Jude Medical v a l v e s were used a s both i n l e t and o u t l e t va lves .

During s y s t o l e t h e s e p t a l w a l l swings toward the o u t l e t , reducing t h e volume of t h e v e n t r i c l e ; at. t h e same t i m e t h e volume of t h e a t r i u m i n c r e a s e s and f i l l s w i t h blood. I n d i a s t o l e t h e s e p t a l w a l l swings toward t h e a t r i a l i n l e t , decreas ing t h e volume of the a t r i u m ; a t the same time the i n l e t v a l v e i s opened and blood i n t h e a t r i a l chamber moves i n t o t h e v e n t r i c u l a r chamber. I t can achieve quick f i l l i n g of a v e n t r i c u l a r c:hamber. Therefore , i t can d i s c h a r g e t h e maximum st.roke volume even i n a r e g i o n of h i g h p u l s e r a t e .

I ts performance was t e s t e d i n a mock c i r c u l a t o r y system. The o u t p u t f low r a t e i-ncreased i n p r o p o r t i o n t o t h e pump b e a t r a t e up t o 150 beat /min. The maximum o u t p u t f low r a t e was 1.0 L/min. Nobuyuki Kabei, Yasuhisa Sakura i , and K i i c h i Tsuchiyak. I n s t . of BME, Tokyo Women's Medical Ccillege, Tokyo Japan. * Dept. of Mechanical Xrigineering, WAseda Univ., Tokyo, Japan.

138 A NOVEL MTRACORPOREAL CIRCUIT FOR THE Ex VIVO EVALUATION OF TUBULAR BIOMATERIALS

I n an assessment of t h e blood c o m p a t i b i l i t y of b i o m a t e r i a l s , t h e r e a r e advantages i n having a r e l i a b l e e x v ivo procedure and, i n t h s r e s p e c t , t h e r e i s a requi rement f o r a procedure s u i t a b l e f o r m a t e r i a l s i n t u b u l a r form. For t h i s purpose an e s t a b l i s h e d ra t hemoperfusion c i r c u i t h a s been modi f ied t o enable t h e e v a l u a t i o n of t u b u l a r bio- m a t e r i a l s . Cannula t ion i s v i a t h e c a r o t i d a r t e r y and jugular v e i n and t h e t e s t procedure i s performed w i t h t h e a n i m a l i n an u n r e s t r a i n e d , consc ious s ta te . F e a t u r e s of t h e procedure a r e t h e i n c l u s i o n of a s e t r e c o v e r p e r i o d p r i o r t o t r e a t m e n t and t h e a b i l i t y to perform ext racorpor- eal c i r c u l a t i o n on c o n s e c u t i v e days. Cons is tency of per foruance and minimisa t ion of o p e r a t o r dependency a r e achieved by c o i l i n g t h e t e s t m a t e r i a l round a metal mandrel. h a s been used t o compare 3 poly(v iny1 c h 1 o r i d e ) s c o n t a i n i n g d i f f e r e n t p l a s t i c i s e r s and formula ted t o t h e same degree of s o f t n e s s . Levels of e r y t h r o c y t e s and p l a t e l e t s and l e u c o c y t e a l t e r - a t i o n s were monitored d u r i n g a . 4 hour per fus ion . The r e s u l t s demonstrated that t h e procedure i s s u i t a b l e f o r d e t e c t i n g t h e i n f l u e n c e on blood of d i f f e r e n t polymers and i s r e l e v a n t t o t h e eval- u a t i o n of t u b u l a r b i o m a t e r i a l s p a r t i c u l a r l y those i n t e n d e d f o r e x t r a c o r p o r e a l a p p l i c a t i o n .

The procedure

Caro l J o n e s , James M.Courtney,Colin R.Blass , Mohammed A s l a m , Ca lv in J.Pyan L I n i L o f Strathclyde,Glasgow,U.K., Hydro Polymers, U.K. , Hammersmith H o s p i t a l , London, U.K.

140 CHEMICAL AND MECHANICAL CHANGES OF SEGMENTED POLYURETHANE AFTER IMPLANTATION

I n t h e c o u r s e of o u r s t u d y t o e v a l u a t e i n v ivo long-term s t a b i l i t y of polymeric m a t e r i a l s , w e have r e p o r t e d t h e b iodegrada t ion of polymers by i n v i t r o o r i n v ivo exper iments . The o b j e c t i v e of t h e work is t o c l a r i f y t h e e f f e c t of implant t i m e on p r o p e r t i e s of p o l y e t h e r u r e t h a n e u r e a . The changes i n mechanical p r o p e r t i e s , molecular weight a n d s u r f a c e c h a r a c t e r i s t i c s of t h e r e t r i e v e d polyure thane f i l m s w e r e examined.

Biomer was used a s segmented polyure thane i n t h i s s tudy. T e s t specimens with 15x15 mm w e r e c u t from c a s t f i l m and au toc laved . The specimens w e r e i n s e r t e d i n t o subcutaneous pockets i n t h e back of Wistar ra ts . A f t e r i m p l a n t a t i o n f o r up t o 2 4 months. b o t h t h e implants and sur rounding t i s s u e s w e r e removed a n d f i x e d i n f o r m a l i n . S e v e n t e e n specimens w e r e r e t r i e v e d from t h e t i s s u e s .

The s u r f a c e s of r e t r i e v e d s p e c i m e n s w e r e a l m o s t f r e e of d e p o s i t s o r c r a c k s , a n d a n y f r a g m e n t a t i o n was n o t s e e n . However, o p a c i t y w i t h i n f i l m s developed w i t h t i m e . E longat ion a t f a i l u r e g r a d u a l l y d e c r e a s e d w i t h t i m e o f implanta t ion . There w a s no a p p r e c i a b l e change i n t e n s i l e s t r e n g t h d u r i n g t h e per iod . The ATR-FTIR s p e c t r a o f i m p l a n t e d s p e c i m e n s s i g n i f i c a n t l y c h a n g e d w i t h t i m e . A b s o r b a n c e r a t i o of non- hydrogen bonded u r e t h a n e carbonyl ( 17310-') to hydrogen bonded one( 1707m-I) tended t o d e c r e a s e g r a d u a l l y w i t h t i m e a n d CH2 peak (1367cm-I1 o f p o l y e t h e r a l s o d iminished r e l a t i v e l y .

The r e s u l t s o b t a i n e d s u g g e s t t h e s u r f a c e d e g r a d a t i o n of t h e polyure thane . Yoshinori Kadoma, Yohji I m a i D i v i s i o n of F u n c t i o n a l P o l y m e r , I n s t i t u t e f o r Medical and Dental Engineer ing , Tokyo Medical and Dental U n i v e r s i t y , Tokyo, Japan


318 ABSTRACTS OF THE Vllth WORLD CONGRESS

141

143

DRUG RELEASE SYSTEM CONTROLLED 3Y BIO- SEhiSOR AND STIKULE RESPOXSIVE EYDROGEL

On-off switching drug release systems controlled by a bio-sensor and a stimule- responsive hydrogel were studied. Certain enzymes such as glucoseoxidase were immobilized in a thin layer on the surface of gate part of ISEFT microsensor by coating and polymerization of vinyl monomers. On the other hand, various kinds of electrically sensitive and responsive hydrogels were >repared by polymerization and crosslinking of monomers such as iso- propyl acrylamide and methacrylic acid. Certain drugs such as iasulin were entrapped in the hydrogel. Then, the micro-bio- sensor >art was connected with drug including hydrogel ?art through multiplier to forn a s t i r n u l e responsive controlled release system. It was fonnd that, when the bio-sensor ?art caught glucose inpouring,pH change due t o gluconic acid formation gave electrical output and caused the followed insulin release. The optimum conditions and system compositions were investigated f o r the reversible on-off switching of drug release. Considerable sensitivity and reversibility was obtained by improvements of enzyne immobilization conditions and hydrogel copolymer compositions.

Isao Raetsu, Yugihiko :Taka, Yasuji Korita* and Akira Otori Res.Inst.Sci.Technol.,Kinki University, Osaka,Japan.*Senju Pharrn.Co.,Osaka,Japan.

A NOVEL KULTI-LAYERED COKPOSITE HOLLOK FIRER KZY5RANE FOX ARTIFICIAL LUXG

The ?as t r a n s f e r per foraances i n gas-ne,+nbrane- l i q u i d system were i n v e s t i s a t e d with var ious nerhranes and it was found t h a t t h e 0 2 qas f l i lx it. gas-menbrafie-iiquid s y s t e z is to be s e t u r a t e d linder t h e c e r t a i n c o n d i t i o n of l i q u i d veloci'y, irhen t h e 0 2 gas f l u x (Fg-g) of gas-menbraiie-%as becomes more than 1.0 x 10-5 ( c n j (STT) cm-2 2 - 1

(cmfiq)-i) ,FCg-g. This was expla ined a s follcus; t h e r e s i s t a n c e of boGndary l a y e r a t l i q u i d phase is doninant , i . e . , t h e m n b r a n e r e s i s t a n c e is n e g l i g i b l e i n t h e reg ion of Fg-q g r e a t e r than FCg-g. ConsecueEtry, Fg-g of nernbrane should be les igned t o be g r e a t e r than FCgr-q, t o s s t i s f y t h e gas exchawp performance r e q u i r e d f o r x t i f i c i a l lung. Based on b a s i c a n a l y s i s , we deVelOQec! L m v s l

t h r y e layered composite holiow f i b e r membrana (MXF) a t which t h i n donce l a y e r (hono=er:eous mexbrane) is inser:ed betwsen two nicroporo-s l a y e r s . It was shown thrGUgh t h e ?va lua t ion i n v i t r o

t h a t MEF has good Sas t r a n s f e r perforstances f o r iong-term p e r f u s i o n compared v i t h convencicnai n ic rsporous nembrane and i n a d d i t i o n , no s f r u n leakage was observed and vapor loss was smal i enough. These c h a r a c t e r i s t i c s silggest t h a t MBF i s q u i t e u s e f u l f o r long-term usage siich ts ECHO.

Zun Kano, Makoto tichida, Takayuki Hirti, Haruhiko Yosida, Kensuke Kanada, Toru Takenura C e n t r a l Xesearch Lavoratory, Mi tsobish i Raycn CC., L td . , Ohtake, %iroshim&, Japan

I42

144

USE OF l?J&3JAPiS.~SIS IB COIi'lsEX TWATL'l.ENT OF CHILDFXM S U P W R I N G PROM CRIJSH SYNUROIm \re used plasrnapheresis in f i v e ch.i.1- dren eged 6-14 with The chiliireii vnderwent p r e o p e r a t i o n a l complex tsestment with antibiotics, RBC transfusion, rhealogic active s0l.u- ti on s he mo dial. y s i 8 and he nzo t ran 3 fu Y - ion.This had not brov-ght about any essential improvement in the petients' state./.nuria p e r s i s t e d and intoxfcat- i o n increased. The patient sl state mz- de us app1.y plasmapheresis course of 1-6 procedures.During eecb procedure ne r e m o v e d 70-75% o f ideal volu!n.t of circulating plesma . Our pla.somphe- resis resulted in disappearence of rnyoglobin from the b lood and urjne, normalization of blood clotting, decrease of middle rriolecules level . T h u s pl.3 smapheresis combined w i t h compies therapy made it possible to cure (eliminate) anuria cmo! DIG-syndrome, and it markedly reduced in toxicstion. Kalinln 1J.N. ,Konovalov G.A. ,Belyaeva I.D.,Petrova V . I . All-Union Scientific Centre f u r h'ac- matology o f the USSR Ministi-.y of Health ,PJl-Union Cardiology Research Centre of the USSR 4-cademy of Medi-cal S c i ence s I Mo sc ow.

c m & sgndrome,

B E N E F I C I A L CHARACTERISTICS OF LOW MOLECULAR WEIGHT HEPARIN ( L H ) AS AN ANTICOAGULANT FOR EXTRACORPOREAL CIRCULATION(ECC)

an t icoagulant f o r E C C , LH was applied t o 33 regular hemodialysis(HD) pa t i en t s and 5 cases who required plasma exchange(PE). Half l i f e o f LH i n H D pa t i en t s was ca lcu la ted t o be 246+77 m i n , which was 2 times longer than t h a t of normgl cont ro l . The half l i f e was a l so about 2 times elongated compared t o t h a t of conventional heparin(CH). Owing t o the long ha l f l i f e , H O could be completed only by the single in j ec t ion of LH a t the s t a r t of H O . Minimum requirement of LH f o r HO on s ing le in j ec t ion was determined t o be 8.06 anti-Xa(aXa) U/kg d ry weight xHD hour, which was l e s s than t h a t on continuous infusion o f LH or C H ( p < O . O l ) . Hemostatic time a f t e r removal o f needle was s i g n i f i c a n t l y shortened i n s ing le in j ec t ion of L H . When the equal doses of L H and CH was u t i l i z e d , higher aXa a c t i v i t y was maintained i n L H , while the prolongation of aPTT and ac t iva ted coagulation time was l e s s e r i n L H than i n C H . There was no d i f fe rence i n l i p o l y t i c ac t iv - i t y and the e f f e c t on p l a t e l e t function between LH and C H , however r e f l e c t i n g the lower minimum re - quirement f o r H D , these adverse e f f e c t s were prac- t i c a l l y suppressed in L H . In P E , continuous infu- s ion method was necessary i n both LH and C H , because o f the elimination in to the separated plasma.

e spec ia l ly f o r the pa t i en t s w i t h high bleeding risk, and i n H D , i t can be administrated more simply than CH. Naoaki Kanamori, Kyoko Kino, Eriko Kinugasa, Tadao Akizawa, Shozo Koshikawa Fujigaoka Hospital , Showa University Yokohama, Japan

To c l a r i f y the c h a r a c t e r i s t i c s of LH as an

These r e s u l t s i nd ica t e t h a t LH i s more useful


145

141

ABSTRACTS OF THE

THE EFFECT OF LEFT HEART ASSIST DEVICE FOR THE HEART - A COMPARATIVE STUDY OF ASYNCHRONOUS P U L S A T I L E , SYNCHRONOUS PULSATILE, A N D NONPULSATILE LEFT HEART BYPASS.-

I t has been d i s c u s s e d which i s t h e b e s t mode f o r the o p e r a t i o n of t h e l e f t h e a r t bypass. So we i n v e s t i g a t e d t h e e f f e c t s on c a r d i a c performance of L H B . T h r e e d i f f e r e n t LHB mode were used i n Mongre l d o g s a t t h e same time : a s y n c h r o n o u s p u l s a t i l e , s y n c h r o n o u s pulsatile, a n d n o n p u l s a t i l e mode. I n t h e s e modes, t h e pump f low w a s changed and then changes in AoSP, LVSP, LAP, C O , P T B , E V R , LVW, f l o w of LAD, Ex02 and MV02 were s i m u l t a n e o u s l y measured . I n a s y n c h r o n o u s p u l s a t i l e mode,

The r e s u l t s o b t a i n e d i n t h i s e x p e r i m e n t were 1 ) I n h igh LHB f l o w , t h e n o n p u l s a t i l e LHB W ~ S more u s e f u l t o m a i n t a i n f l o w a n d more e f f e c t i v e i n reducing t h e c a r d i a c work than t h e o t h e r modes o f LHB. H o w e v e r t h e r e was no d i f f e r e n c e be tween t h e e f f e c t s on t h e c a r d i a c p s r f o r m a n c e when t h e LHB f l o w was i n c r e a s e d h i g h e r . 2 ) I n c o n t r a s t , when t h e LHB f l o w was l ~ w , no d i f f e r e n t i a l e f f e c t was observed between t h e hernodynamic p a r a m e t e r s . 3 ) I n s y n c h r o n o u s p i l s a t i l e mode, f low of t h e coronary a r t e r y w a s i n c r e a s e d in middle and high LHB f low.

T h u s , i t i s c o n c l u d e d t h a t a l t h o u g h t h e c i r d i a c work was r e d u c e d i n a l l modes of L H B , when t h e b y p a s s f l o w w a s m a i n t a i n e d h i g h , t h e n m p u l s a t i l e LHB showed t h e b e s t performance of a l l modes of LHB. However the high coronary f low i n svnchronous p u l s a t i l e mode would b e n e f i t t h e

phase a n a l y s i s was used.

damaged myocardium. Y J O Kanamori, Takatsugu Simono, Kuniyosi Tanaka, Isao Yada, Minoru Kusagawa Depart . of Thoracic Surgery Mie Univers i ty School of Medicine, Tsu, Japan

ELECTROCHEMICAL PHENOMENA I N T H E H E M O P E R - FUSION O V E R A C T I V E CARBONS

P h y s i c a l c h e m i s t r y o f t h e p r o c e s s e s o c - c G r i n g i n t h e s y s t e m " c a r b o n - b o d y f l u i d " i n c l u d e s n o t o n l y s o r p t i o n b u t a l s o o t h e r p h e n o m e n a o f e l e c t r o c h e m i c a l n a t u r e . T h e l r t t e r c a n b e r e s p o n s i b l e f o r a d d i t i o n a l c o n t r i b u t i o n i n t h e i r d e t o x i f y i n g a c t i o n ( c a t a l y s i s i n t h e r e d - o x r e a c t i o n s ) a n d i n c o n t r a r y c a n l e a d t o some c o m p l i c a t i o n s n a m e l y , b l o o d d e o x y g e n a t i o n , damage o f b l o o d c e l l s e t c . We s t u d i e d v a r i o u s e l . e c t - r o c h e m i c a l p a r a m e t e r s o f d i f f e r e n t c a r b o n s ( ~8 o l a r i s a t ion k i n e t i c s , e 1 e c t r o d e p o t e n t - i a l , z e r o c h a r g e p o t e n t i a l ) . E l e c t r o s t a t i c i x t e r a c t i o n b e t w e e n b l o o d c e l l a n d p o s i t i - v e i y c h a r g e d c a r b o n s u r f a c e a c c o m p a n i e d w i t h o x y g e n c h e m i s o r p t i o n a r e p r o b a b l y t h e m a i n c a u s e o f t h e t r a u m a t i z i n g a c t i o n o f a c t i v e c a r b o n s on t h e w h o l e 'b lood . To m i n i rnize t h i s e f f e c t a d d i t i o n a l p r e t r e a t m e n t o f c a r b o n s b e f o r e h e m o p e r f u s i o n i s n e c e s s a r y . P o l a r o g r a p h i c d a t a e v i d e n c e d t h e f a c t t t a t some a c t i v e c a r b o n s h a v e i n i t i a l e l e c t r o d e p o t e n t i a l s u f f i c i e n t t o a c c e l e r a t e a l o t o f r e d - o x r e a c t i o n s a t t h e p h y s i o l o g i c a 1 pH v a l u e s e s p e c i a l l y o x i d a t i o n o f b i l l - r L b i n a n d u r i c a c i d .

We d e s i g n e d e l e c t r o c h e m i c a l m a s s - e x c h a n @.r'r i n w h i c h s p h e r i c a l b e a d s o f s y n t h e t i c c h a r c o a l s SCN a n d SCS a r e u s e d a s " p s e u d o - t c 8 i l i n g l a y e r " - t y p e e l e c t r o d e . T h i s e x c h a n c c ' r i s more e f f e c t i v e i n t h e b l o o d d e t o x i c a t i o n omp pared t o t h e u s u a l s o r b e n t c o l u m n . K a r t e l N . , M a r o r e s k u Y . P o p o v V . , T a r a n e n P o Y . . M i k h a l o v s k v S . . s t r e l k o V . I r s t i t u t e G e n e r a l I n o r g . C h e m i s t r y , C i t y t c ~ s p i t a l , K i e v , USSR

VIIth WORLD CONGRESS 319

146 GOM3INED DETOXIGATIOQ SYSTCPI OF A NEW HEMODIAFILTRATION (EDF) AND PLASMA EXCHANGE(PE) FOR FULPIINANT VIRAL, IIF,PATITIS(FVH)

PE i s e f f e c t i v e in supply ing h e a l t h y plasma congonents , however , i t s e l i m i n a t i n g c a p a c i t y f o r t o x i c subs tances i s i n s u f f i c i e n t . HDF wi th high p e r f o r n a n c e membranes can e f f i c i e n t l y remove s u b s t e n c e s , which a r e assumed t o induce h e p a t i c encephalopathy.We have a p p l i e d a new combination w i t h PE and HDF t o t h e p a t i e n t s of FVH.

I n 1980-86, 4 ceses of B type and 1 case of A type were t r e a t e d by PE. From 1987, 6 cases of non B non B(I!AXD) type an5 4 cases o i B t:rpe were t r e a t e d by the PE and HDF, when prothrombin time WGS lower than 40% and/or h e p a t i c coma progressed over grade 11. HDF was performed w i t h polymethyl riethacrylate(PNKA) membrane d i a l y a e r , u s i n g 10- 15L of b icerbcnete c o n t a i n i n g s u b s t i t u t i o n f l u i d and s tandard b icarbonate d i a l y s a t e .

The 5 cases were t r e a t e d by 4.622.0 times of PT; and only one of B type was cieceased. Recent 10 cases were t readed by 15.7522.2 t imes o f PG and 17 .2+21.8 t i n e s of HDF. The HDF c o u l d r e c o v e r consciousness c l e a r l y i n a l l p a t i e n t s who d id-n ' t respond t o PE, except a n old p a t i e n t of NANB type . These p a t i e n t s d u r i n g PE and HDF had a chance f o r a d d i t i o n a l therapy i n c l u d i n g i n t e r f e r o n i n PAIiE type . By t h s e s t reet ,ment ,3 cases of NANB type and 2 c a s e s of B type could s u r v i v e ( 5 0 % ) .

These r e s u l t s i n d i c a t e t h a t our new a r t i f i c i a l l i v e r s u p p o r t t h e r a p y a c h i v e d a h i z h s u r v i v a l rete not on ly B type but a l s o non A non 3 type of fu lminant v i r a l h e p a t i t i s . z h i z e r u K a n e s a k a , T a d a o A k i z a v a Y o s h i ! < i Takahashi , flakoto Yoshiba, Shozo Xoshikawa. 3 n e r g e n c y C e n t e r and I n t e r n a l t i e d i c i n e , Shoiia U n i v e r s i t y Fuj igaoka H o s p i t a l , Yol:oha~;ia ~ Japan ~

148 BASIC RESEARCH ON A EIETABOLIC SUPPORT DEVICE FOR A HYBRID ARTIFICIAL L I V E R .

A r t i f i c i a l l i v e r s u p p o r t s such a s h e m o d i a l i s i s , hemoperfusion and plasma exchange have r e c e n t l y been c l i n i c a l l v used f o r t h e t r e a t m e n t of s e v e r e l i v e r d i s e a s e s . However t h e outcome of t h e s e t r e a t m e n t s have not been improved a s expected. Therefore , a hybr id type of a r t i f i c i a l l i v e r i s expected t o be another way of l i v e r supnor t . I n our department , a pro to type of hybr id a r t i f i c i a l l i v e r suppor t system us ing i s o l a t e d hepatocytes h a s prev ious ly been developed. I n t h i s system, t h e v i a b i l i t y of hepa tocytes could not be maint- a ined over t e n hours because of a f l o a t i n g system. The purpose of t h i s s t u d y is t o e v a l u a t e t h e u s e f u l n e s s of h e p a t o c y t e s c u l t u r e s u b s t r a t a t o main ta in t h e f u n c t i o n of hepa tocytes f o r more long t i m e .

The h e p a t o c y t e s were obta ined from r a t s weghing about 2OOg by c o l l a g e n a s e d i g e s t i v e method. Hepa- t o c y t e s c u l t u r e s u b s t r a t a such a s c o l l a g e n , bio- m a t r i x l ac tose -ca r ry ing -po lys ty rene (€ 'VLA) , micro- c a r r i e r and ca lc ium-a lg ina te g e l were examined on c e l l c u l t u r e system and s p i n n e r f l a s k t e s t s . Biomatr ix w a s p repared from dog l i v e r by a method of Rojkind.

I n d i s h c u l t u r e exper iments , the time f o r c e l l a t tachment was shor tened by c o a t i n g t h e d i s h wi th c o l l a g e n , PVLA and b i o m a t r i x . I n s p i n n e r f l a s k t es t s , metabol ic a c t i v i t i e s were increased by us in^ microcar r ie r , b i o m a t r i x and Ca-alginate g e l .

I n c o n c l u s i o n , hepa tocytes c u l t u r e s u b s t r a t a is u s e f u l t o main ta in t h e i r f u n c t i o n s i n a hybr id a r t i f i c i a l l i v e r system. S h i n i c h i Kasai, Te tsu Yamamoto, Aki tosh i Kakisaka, Idar ih i ro Ohe, Michio I l i t o , 2nd Dept. of Surgery, Asahikawa t led ica l C o l l e s e , Asahikawa, Japan



149

151

I N VITRO AND I N V I V O EVALUATION OF THE NEWLY DESIGNED Bm VALVE VENTRICULAR ASSIST DEVICE.

A newly designed ball v a l v e has been d e v e l o p d f o r OUT a i r -dr iven sac-type vent r icu lar assist device (VAD) instead of BjSrkShi ley valve. The VAD should supply the wide rang5 of the flow assis tance accord.ing to the required cardiac assis tance a f t e r the f a i l i n g natural h e a r t . O u r p r e v i o u s f l o w a n a l y s i s and i n v i v o evaluat ion revealed that the thrombus generation had tendency t o occur i n the adjacent l e s i o n t o the v a l v e p r o s t h e s i s e s p e c i a l l y on c o n d i t i o n o f t h e low f l o w rate. Therefore, the thromb-resistancy as the t o t a l VAD system would be l i m i t e d by t h e f l u i d m e c h a n i c a l c h a r a c t e r i s t i c s of t h e v a l v e i n t h e low f l o w r a t e condition.

The newly designed b a l l v a l v e was compred w i t h the Bj i j rkShi ley v a l v e prosthesis i n the fluid-mechanical c h a r a c t e r i s t i c s by means of t h e q u a n t i t a t i v e f l o w v i s u a l i z a t i o n technique e s p c i a l l y on condition of the low f l o w ra te and i n t h e thrombo-resis tancy by t h e chronic animal experiments w i n g a d u l t s goats. I n these in v i t r o and in v ivo sbxlies, the higher f low v i l o c i t y and the higher shear s t r e s s even on condition of the low f low rate and more e x c e l l e n t thrombo-resistancy w e r e o b s e r v e d t h a n t h o s e of t h e B j G r k - S h i l e y p r o s t h e s i s . It is concluded t h a t our newly des igned b a l l v a l v e matches w e l l with the requirement of VAE and has suf f ic ien t thrombo-resistancy f o r t h e c r i n i c a l use.

Yoshiaki Katahira, Shinichi Nitta, Tomoyuki Yambe, Taro Sonobe, Motonao Tanaka, Makotc Miura*, Naoshi %to', HiksK hi*, ~ ~ ~ f i ~ N%=~**, Ryuichiro Yodaait Res. I n s t . f o r Chest D i s . & Cancer, Tohoku Univ., Sendai, Japan. *Dept. of Thoracic Surg., Sch. of Med., Tohoku Univ. **Nippn %on Co.,Ltd.

PREDOMINANCE OF BIOPROSTHESES FOR ISOLATED AORTIC VALVE REPLACEMENT -A COMPARATIVE STUDY BETWEEN MECHANICAL AND BIOPROSTHETIC VALVE- Comparative long-term performance c h a r a c t e r i s t i c s of mechanical v a l v e s and b i o p r o s t h e t i c v a l v e s were analyzed r e t r o s p e c t i v e l y f o r p a t i e n t s undergoing i s o l a t e d a o r t i c v a l v e replacement from 1968 t o 1987. 167 p a t i e n t s r e c e i v e d e i t h e r mechanical(n= 82) o r b i o p r o s t h e t i c ( n = 8 5 ) v a l v e s . The cumula t ive follow-up w a s 926 pa t ien t -years (mean 6.124.7 y e a r s , ranging from 0 .5 t o 20.2 y e a r s , 100% complete fol low-up) . A c t u a r i a l s u r v i v a l r a t e , i n c l u d i n g o p e r a t i v e d e a t h , a t 10 y e a r s was 74+7% f o r mechan- i c a l and 7737% f o r b i o p r o s t h e t i c v a l v e r e c i p i e n t s . The r a t e s of p a t i e n t s showing no s i g n s of thromboembolism, s t r u c t u r a l v a l v e f a i l u r e , p r o s t h e t i c v a l v e e n d o c a r d i t i s , and v a l v e re rep lacement a t 10 y e a r s were 77571, l o o % , 9652% and 9533% f o r mechan- i c a l , and 94+4%, 83+8%(pc0.05) , 88+5% and 7558% ( ~ ~ 0 . 0 5 ) f o r b i o p r o s t h e t i c v a l v e r e c i p i e n t s , respec- t i v e l y . Thromboembolism occured more f r e q u e n t l y i n t h e mechanical v a l v e r e c i p i e n t s ( K O . O l ) , and s t r u c t u r a l v a l v e f a i l u r e i n t h e b i o p r o s t h e s e s r e - c i p i e n t s ( p d . 0 5 ) . There was no m o r t a l i t y a t t h e t i m e of v a l v e re rep lacement . Most of t h e b iopros- t h e s e s r e c i p i e n t s r e c e i v e d no a n t i c o a g u l a t i o n beyond 3 months p o s t o p e r a t i v e l y . t i o n i n t h e l a t e p o s t o p e r a t i v e p e r i o d was n o t r e q u i r e d any more f r e q u e n t l y f o r b i o p r o s t h e t i c (31.3%) t h a n f o r mechanical v a l v e r e c i p i e n t s ( 3 . 2 % ) ( ~ ~ 0 . 0 1 ) . These r e s u l t s show t h a t b i o p r o s t h e s i s i n t h e a o r t i c p o s i t i o n e x h i b i t s a superb ant i thrombo- g e n i c i t y and may i n t r o d u c e a drug f r e e s t a t e , though i t s l i m i t t e d d u r a b i l i t y r e q u i r e d r e o p e r a t i o n . Yoshi to Kawachi, Kouichi Tokunaga D i v i s i o n of Card iovascular Surgery , Research I n s t i t u t e of Angiocardiology, Kyushu U n i v e r s i t y , F a c u l t y of Medicine, Fukuoka, Japan

C a r d i a c medica-

150 MOLECULAR DESIGN OF LYMPHOCME SEPARATOR : NOVEL SYNTHETIC ADSORBENT FOR T CELL SUBSETS

Materials with specific recognition toward a particular cell population has a great utility as column adsorbent for cell separation in therapy and diagnosis. Through our systematic study on cell-materials interaction, we have found that poly(2- hydroxyethyl methacrylate)/polyamine graft copolymer (HA) selectively adsorbed B cells out of a heterogeneous mixture of lymphocyte subpopulations.') Based on this finding, wehave further designed in this study a partially quaternized HA copolymer (HQA) to achleve more detailed resolution of lymphocyte subpopulation, including T lymphocyte subsets.

Adsorbent was prepared by coating HQA on glass beads. Then, lymphocyte suspension prepared from mesenteric lymphnode was passed through a column packed with adsorbent thus prepared. Immuno-fluorescence assay using FITC-labeled monoclonal antibody revealed that at pH 7.4 HQA preferentially adsorbed non-helper T cells as well as B cells. Consequently, helper T cell enriched population was obtained as column effluent. Resolution of T cell subsets by HQA was considerably pH-dependent, and at slightly acidic condition (pH - 6.8) helper T cells in turn showed higher affinity to HQA than non-helper T cells, indicating a possibility of pH-regulative resolution of T cell subsets. These results Indicate that newly designed HQA has a high feasibility as an adsorbent for lymphocyte separator used in lmmunomodulation therapy. 1) K. Kataoka, Artif. Organs 51 1 (1988).

HQAX Kazunori Kataoka. Yasuhisa Sakurai, Takuya Kadowaki. Teiji Tsuruta lnstitute of Biomedical Engineering, Tokyo Women's Medical College, Tokyo, Japan

152 MECHANICAL SIMULATOR TO QUANTITATE THE LEVEL OF I N V I V O MYOCARDIAL DAMAGE

[PURPOSE]: 1) To q u a n t i t a t e t h e e f f e c t of changes i n t h e c o n t r a c t i l i t y of t h e r e g i o n a l ischemic a r e a on t h e t o t a l c a r d i a c performance and 2) t o e v a l u a t e t h e e f f e c t of an LVAD o r s u r g i c a l removal of t h e ischemic p a r t on t h e r e g i o n a l l y i schemic h e a r t (RIH). [METHOD] A c a r d i a c model c o n s i s t i n g of i schemic and h e a l t h y p a r t s was developed by connec t ing two pneumatic pusher- p l a t e a r t i f i c i a l h e a r t s (PPHA) i n p a r a l l e l . The pressure-volume r e l a t i o n s h i p (PVR) of t h i s model was o b t a i n e d t o s t u d y t h e e f f e c t of reg ion- a l i schemia . [RESULTS] 1) Because E ( t ) , t h e s l o p e of r e l a t i o n s h i p of one t ime i n each cyc le i s c o n s t a n t , ( F i g . 1 ) t h e PPHA has F ig . 1 s i m i l a r t i m e vary ing e l a s t i c char-,, a c t e r i s t i c s a s t h e n a t u r a l h e a r t , ' " t h u s i t s c o n t r a c t i l i t y c a n be e s t i m a t e d from t h e e n d s y s t o l i c $ m o

PVR (ESPVR). 2 ) The s l o p e of ESPVR, Emax, d e c r e a s e s i n t h e i-4

t o t a l ischemic h e a r t model. 3 ) I n 50 IW II

t h e lower a f t e r l o a d r e g i o n , A , ( F i g . 2 1 , 1/Emax of t h e R I H can be Fig.2 e s t i m a t e d a s a l i n e a r sum of 1 1 Emax of each chamber, w h i l e i n t h e h i g h e r a f t e r l o a d r e g i o n B, by:,- t h a t of t h e h e a l t h y p a r t . [CON- : CLUSION] By comparing n a t u r a l h e a r t PVRs t o t h o s e of t h i s model, W.I.

prognos is can be made r e g a r d i n g che e f f e c t s of an LVAD o r s u r g e r y on t h e R I H . Osamu Kawaguchi, *Setsuo T a k a t a n i , Hidemiki S a s a k i , Yokoyama Yuki fusa , Tuyoshi F u j i t a , Tetuzo Akutu, N a t i o n a l C a r d i o v a s c u l a r Center H o s p i t a l *Cleveland C l i n i c A r t i f i c i a l Organ Foundat ion


ABSTRACTS OF THE VIIth WORLD CONGRESS 32 I

153 THE SHEAR STRESS DEPENDENT SELECT- IVITY I N THE ADHESIVE PROTEINS REQUIRED FOR PLATE- LET AGGREGATION

I n c i r c u l a t i n g b lood , p l a t e l e t s a r e exposed t o d i f f e r e n t l e v e l s o f shear s t r e s s i n d i f f e r e n t d i s - t r i c t s o f t h e v a s c u l a r system. I n t h i s s tudy , p l a - t e l e t agg rega t ion induced by v a r y i n g shear s t r e s s was measured i n a cone and p l a t e v iscometer adapted f o r con t inuous r e c o r d i n g o f l i g h t t ransn . i ss ion u s i n g p l a t e l e t r i c h plasma (PRP) f rom p a t i e n t s w i t h c o n g e n i t a l b l e e d i n g d i s o r d e r s o r normal PRP t r e a t e d w i t h s p e c i f i c monoclonal an t i body . A t low shear, 18 dyne/cm2, p l a t e l e t agg rega t ion was d e f e c t i v e i n p a t i e n t s c o n g e n i t a l l y d e f i c i e n t i n f i b r i n o g e n o r p1 a t e 1 e t membrane g l y c o p r o t e i n I I b / I I l a (GPI I b / I I I a ) b u t normal i n p a t i e n t s d e f i c i e n t i n GPIb o r vWF. F i t h i g h shear, 108 dynelcm2, however, agg rega t ion was normal i n t h e a f i b r i nogenemic p a t i e n t and was d e f e c t i v e i n p a t i e n t s d e f i c i e n t i n GPIb, G P I I b / I I I a o r vWF. Ant i -GPIb a n t i b o d y known t o i n h i b i t vWF b i n d i n g t o t h i s r e c e p t o r b locked aggrega t ion i n a h i g h shear f i e l d , b u t no e f f e c t a t low shear . A n t i - G P I I b / I I I a an t i body , on t h e o t h e r hand, i n h i b i t e d aggrega t ion a t l ow and h igh . Anti-vWF p e p t i d e a n t i - body known t o i n h i b i t vWF b i n d i n g t o G P I I b / I I I a , b u t n o t t o GPIb, comp le te l y i n h i b i t e d aggrega t ion o n l y a t h i g h shear . These f i n d i n g s i n d i c a t e t h e shear s t r e s s dependent s e l e c t i v i t y i n t h e adhesive p r o t e i n r e q u i r e d f o r p l a t e l e t agg rega t ion .

K.KawaKami, M.Fukuyama, K.Sakai, I.Itagaki*, K.Kawano**, M.Handa** and Y.Ikeda**. Iept. Chem. Eng. Waseda Univ., Toray Industries I n r . and School of Med. Keio Univ.**

155 Kt/V & PCR (PROTEIN CATABOLIC RATE) WITHOUT 3LOOD SAMPLES

We have developed a technique for estimating Kt/V b PCR without a single blood (B) sample. The method is based on serial measurements of outlet dialysate (D) urea concentration during dialysis. The fixed volume, single pool urea model, ne- glecting urea generation during dialysis, yields:

CB = CBOe-Kt/V (1 )

CD = CDOe-Kt/V ( 2 )

Substituting K = QDCD/CB in (1) and simplifying:

Zegression of h(CD) vs t yields a straight line with slope -K/V. Kt/V derived from the slope is mathematically equivalent to h(CBpre/CB ost) but may underestimate true Kt/V because of tge assumptions of fixed volume and negligible urea generation during dialysis. Several simple techniques are available to correct for these assumptions and improve the accuracy of this estimate. One can also calculate urea removal from the ln(CD) vs t regression.

CD is the log mean CD obtained from the regression. This approach yields values for removal that are within 1-2% of total dialysate collection. In the steady state, urea generation = urea removal. From urea removal, one can estimate the generation rate and hence the PCR. The above techniques are simple, reliable and reproducible, and have a major advantage of not requiring blood samples.

- Urea removal = QD x 5 x t (3)

P. Keshaviah Baxter Clinical Engineerinn Laboratory 825 South 8th Streit. Suite 722 Yinneapolis, MN 55404 USA

154 DEVELOPMENT OF ADSORBENT FOR FREE-HEMOCLOBIN(F-Hb) It is well-known that renal failure is caused

by hemolysis. Its possible causes may be F-Hb and stroma o r their combined action. We have developed an adsorbent that is capable of selectively adsorbing F-Hb.

The adsorbent(HR-T) was prepared by combining porous silicagel(100A in pore size and 100-200 mesh in particle size), as carrier, with tyramin. as ligand. using silan-coupling agent, as binder. This adsorbent was theoretically based on the adsorption mechanism of haptoglobin. Its adsorption is considered to be achieved by hydrophobic of phenol in tyramin. which adsorbs only F-Hb of dimer. It is provided with selectivity allowing almost no other protains to be adsorbed.

I t s adsorption performance was evaluated by the Freundlich formula. The amount of adsorption of F-Hb by the batch method reached 33mg/HR-Tml. I n plasmaperfusions performed on dogs w i t h O.Sg/kg i v of Hb using column containing HR-T 90ml. 80% reduction in the total Hb was obtained, indicating that the total amount of F-Hb in the blood flow had been adsorbed. In addition, the perfused dogs showed no structure of acute tubular necrosis as obserbed in the non-perfused dogs. This fact has also proved that the removal of F-Hb can lead to the prevention o f renal failure.

I t will be considered that HR-T can be taken up as one of the artificial reticula-endothelium to prevent hemolysis triggering the development into multiple organ failure as well as remove Hb by incorporating it in extra-corporeal circuit. Hideki Kawanishi. Taro Tsuchiya. Takaaki Mochizuki, Mayumi Horibe, Fumio Yoshimoto Akane-Foundation Tsuchiya Hospital, Japan Medical Supply Co. Ltd. Hiroshima. Japan

156 INTRAARTERIAL PERFUSION OF PYRIDOXYLATED HEMOGLOBIN-POLYOXYETHYLENE CONJUGATE(PHP) IN THE HINDLIMB REGION OF ANESTHETIZED DOGS.

To evaluate potential clinical usefulness of a newly introduced oxgen carrying blood substitute (Pyridoxylated Hemoglobin-Polyoxyethylene conjugate :PHP), we perfused the right hindlimb with PHP solution in 7 anesthetized dogs. The right hindlimb region was perfused via the right external iliac artery using extracorporal circuit with a pump at varing flow rates. Collateral flow was minimized by ligating all other major arteries supplying the right hindlimb. PtO was measured using an intravascular PO monitorf636,KONTRON). A P O 2 sensor was inserte2 into gracial muscle. Systemic arterial pressure(SBP) was measured via the internal carotid artery and perfusion pressure (PP) was via the deep femoral artery. Perfusion with PHP solution at a low flow rate (20ml/min) decreased Pt02, but an increase in the perfusion rate(40-50ml/min) started to elevate Pt02 from

PP was increased proportionally to changes in flow rate. The increase in PP during perfusion with PHP solution was smaller than that of blood- perfusion. These results indicate that PHP solution is able to transport significant amount of oxgen to tissue and its lower viscosity vivo,

Yoshitoshi Kida, Takashi Yamakawa, Shyuichi Iwasaki , Nobuyuki Furusho, Yoshihiro Kadowaki, Seinosuke Iwata, Yuichi Gyoutoku, Katsuhide Nishi. Pepartment of pharmacology, Kumamoto University Medical School and Life Science Laboratories, Central Laboratories, Ajinomoto Co.,Inc., Yokohama Japan

pre-perfusion level.

__

Artificial Organs, Vol. 13, NO. 4, 1989


157

159

APPLICATION OF CCD CAMERA FOR FLOW VISUALIZATION OF ARTIFICIAL HEART VALVE

I m p l a n t a t i o n of a r t i f i c i a l h e a r t v a l v e i s a s a f e procedure. However, t h e r e a r e some l a t e v a l v e r e l a t e d compl ica t ions s t i l l remain t o be s o l v e d . Hemolysis and thrombus f o r m a t i o n have been a l l o c a t e d t o t h e hemodynamic d i s t u r b a n c e due t o t h e improper va lve des ign . T h e r e f o r e , a through f l u i d dynamic c h a r a c t e r i z a t i o n and e v a l u a t i o n o f d i f f e r n t a r t i f i c i a l v a l v e i s impor- t a n t f o r t h e b e t t e r v a l v e development.

A new f l o w v i s u a l i z a t i o n system w a s deve loped , which u t i l i z e d a CCD camera (FCD-10, Ikegami Go, Japan) combined wi th a image p r o c e s s i n g d e v i c e ( TV-200, Japan Abio t ronics Go.) . By u t i l i z i n g t h e system, f low f i e l d s downstream o f 22mm S t . Jude Medical , Medi t ronics Hal l , and Duromedics v a l v e s were e v a l u a t e d i n a s t e a d y - s t a t e f low c o n d i t i o n . The t e s t f l u i d was a 48% g l y c e r o l / w a t e r s o l u t i o n wi th a dynamic v i s c o c i t y of O.O5(St) a t room tempera ture . P o l y s t y r e n e beads (Amberi te XAD-7, 20-60 mesh) were used as v i s u a l t r a c e r . The d a t a i n p u t o f t h e b r i g h t n e s s w a s accumulated f o r t h e t ime d u r a t i o n of 1 / 3 , 1 , and 2 seconds . The s t ream l i n e s of t h e t r a c e r were o b t a i n e d c l e a r l y , which showed comformable f low p a t t e r n r e p o r t e d by o t h e r s . The v e l o s i t y p r o f i l e of t h e f i e l d could be c a l c u l a t e d e a s i l y by t h e computer p r o c e s s i n g .

e a s y and u s e f u l method t o s t u d y t h e f l u i d dynamics of a r t i f i c i a l h e a r t v a l v e .

J u k i a k i Kikuta , Yoshinor i Mitamura?, Toshiyuki Shimooka, Shun Murabayashi andToshi Yuhta U n i v e r s i t y of Hokkaido, Tokai Univers i ty*

T h i s new system u t i l i z i n g CCD camera i s a v e r y

EXTRAVASCULAR LUNG WATER DURING HEMODIALY SIS

Several authors reported regarding the cause of hypoxemia during hemodialysis (HD), for example, suppression of respiratory center by acetate, impaired oxygen diffusion, pulmonary vascular leukostasis, although precise mechanism remains still unknown. We examined extravascular lung water (EVLW) in HD patients using Lung Water Computer (MTV 1100@, Nihon Kohden Corporation), based upon the hy- pothesis that the impaired oxygen diffusion might be attri- buted to HD-induced hypoxemia. EVLW was measured by means of double indication method using sodium ions as a non-diffusible indicator and the heat as a diffusible indicator (thermo-saline method), and concurrently hemodynamics were measured by Swan-Ganz catheter, and arterial blood gases were analyzed. In €ID patients, EVLW just before the initiation of HD was significantly greater than healthy control, and it increased after the initiation of HD, then it decreased gradually with time. Both arterial oxygen tension and cardiac output decreased, on the other hand, pulmonary vascular resistance increased during HD. Judging from the increase in EVLW after the initiation of HD, the increase in EVLW is due to increase in pulmonary capillary permiability from unknown mechanism. So-called HD-induced hypoxemia may be related to the increase in EVLW.

[AUTHOR’S NAME1 Kimikawa, M., Teraoka, S., Nakagawa, Y., Itoh, F., Fujita, S., Ohshima, Kawai, T., Agishi, T., Ohta, K.

[INSTITUTION] Kidney Center, Tokyo Women’s Medical College.

158

160

OPTIMAL AND PHYSIOLOGICAL CONTROL FOR A NEW MOVING-ACTUATOR TYPE ELECTROMECHANICAL, TOTAL ARTIFICIAL HEART

In t h e new moving-actuator t y p e e lec t romechanica l t o t a l a r t i f i c i a l h e a r t system, t h e o r e t i c a l a n a l y s i s and c a l c u l a t i o n of s o l u t i o n s for a l l c o n t r o l problems and implementat ion of c o n t r o l system were performed. The c o n t r o l problems a r e s e p a r a t e d i n t o two major s u b j e c t s : v e l o c i t y and position c o n t r o l of a b r u s h l e s s d c motor a s an energy c o n v e r t e r and o u t p u t c o n t r o l of a r t i f i c i a l h e a r t a s a blood pump. The f i r s t p a r t is v e l o c i t y and p o s i t i o n c o n t r o l t o assure t h a t t h e motor f o l l o w s a predetermined opt imal v e l o c i t y p r o f i l e wi th minimal energy consumption, and t o g u a r a t e e z e r o i n i t i a l and f i n a l v e l o c i t y . Using both opt imal c o n t r o l t h e o r y and p a s s i v e a d a p t i v e c o n t r o l system as a robus t c o n t r o l l e r , problem f o r m u l a t l o n and s o l u t i o n independent o f t h e o p e r a t i o n a l environment o f a r t i f i c i a l h e a r t were achieved , arid t h e r e s u l t s of mock c i r c u l a t i o n tests show t h a t t h e o p e r a t i o n under opt imal c o n d i t i o n was always b e t t e r t h a n t h e o t h e r cases wi th lower average i n p u t power and root mean s q u a r e v e l o c i t y error. The pump o u t p u t c o n t r o l is t h e second p a r t and t h i s p a r t p r o v i d e s t h e r e q u i r e d responses of t h e a r t i f i c i a l h e a r t t o t h e t ime-varying phys io logica l demands. The b a s i c requi rements o f t h e responses a r e pre load s e n s i t i v i t y , a f t e r l o a d i n s e n s i t i v i t y . and t h e balanced v e n t r i c u l a r o u t p u t s . To s a t i s f y t h e s e c o n t r o l requi rements , t h e effects of s e v e r a l c o n t r o l parameters and a noninvas ive pre load e s t i m a t i o n were i n v e s t i g a t e d , and t h e r e s u l t s of mock c i r c u l a t i o n tests are very encouraging. Hee C. Kim, Byoung G. M i n , Sang H. Lee, I n Y . K i m , Jong W . K i m , J in W. Choi, J i n T. K i m , Dae Y. Jung Department of Biomedical Engineer ing , Col lege o f Medicine, Seoul Nat iona l U n i v e r s i t y .

PREVENTION OF HEMOGLOBINURIC RENAL FAILURE BY HEMOADSORPTION WITH HR-T

I n t r a v a s c u l a r hemolys is i s an impor tan t cause of a c u t e r e n a l f a i l u r e (ARF). T r a d i t i o n a l r e n a l p r o t e c t i v e measures have been of l i m i t e d success . We e v a l u a t e d t h e r o l e of pigment a d s o r p t i o n by HR-T (Tyramine-s i lane-s i l ica g e l beads) i n t h e p r e v e n t i o n of t h i s form of ARF. One day water depr ived m a l e Sprague-Dawley rats r e c e i v e d an i n t r a v e n o u s i n j e c t i o n of human hemoglobin (Hg) (135mg/100g body weight ) b e f o r e and a f t e r a s i n g l e p a s s a g e over a n HR-T column (6.5g Hg/20g HR-T) fo l lowed by resumpt ion of water i n t a k e (BUN and c r e a t i n i n e i n mg/dl) .

T i m e Hg Untrea ted (N=8) Hg p o s t HR-T (N=10) - BUN C r e a t i n i n e C r e a t i n i n e

0 h r 2422 0.4820.03 2922 0.6420.11 24 h r 141211* 3.5 +_0.55* 1 8 2 l # 0.7t0.02 48 h r 147+26* 3.220.94* 19216 0.56+0.06

Hemoglobin l e d t o azotemia (*P<O.OOl) and d i f f u s e t u b u l a r n e c r o s i s and o b s t r u c t i o n w i t h Hg conta in- i n g casts on h i s t o l o g i c examinat ion. I n j e c t i o n of p o s t HR-T Hg d i d n o t l e a d t o any f u n c t i o n a l o r morphologica l r e n a l d e t e r i o r a t i o n . Indeed BUN d e c l i n e d (#P<O.OS) r e f l e c t i n g t h e resumption of water i n t a k e . W e conc lude t h a t pigment adsorp- t i o n by HR-T i s a n e f f e c t i v e p r o t e c t i v e measure a g a i n s t hemoglobinur ic r e n a l f a i l u r e and i t s a p p l i c a t i o n as an e a r l y hemoadsorbent may a l l e v i a t e t h e t o l l of t h i s c o n d i t i o n .

H a j i m e Kimura, Taro Tsuchiya , Masafumi Sugiyama, G r a z i e l l a Abu-Jawdeh, and S a l i m Mujais . Northwestern U n i v e r s i t y , Chicago, IL , USA and Japan Medical Supply Co., Hiroshima, Japan.



161 TPE GLUED CAYBON FIBE2 ELECTRODES FOR 162 CHANGES I N D I A L Y S I S PROCEDURE BY THE CORRECTION D I .WP:~RAGIVI PAC 1 NG. OF ANEMIA W I T H r - H u E P O

Carbon f i b e r s w i t h f i b r i n g l u e was u s e d a s an e l e c t r o d e f o r t h e s t i m u l a t i o n of phrenic nerves. The e l e c t r o d e s w e r e a ? p l i e d f o r t h r e e mongre l clogs and w e r e t e s t e d t h e e f f e c t i v e n e s s . The r i g h t s i d e t h i r d i n t e r c o s t a l s p a c e was opened w i t h 4 c m i n c i s i o n , and the upper rnediastinum was opened. The carbon lead was g lued t o both phrenic nerves by means of t h e f ibr inogen and thrombin. A pla t inum p l a t e was implanted in the hypodermis a s a c o u n t e r e l e c t r o d e . T h e i n t e r e l e c t r o d e impedance, th reshold c u r r e n t for s t imulat ion and t i d a l volumes were measured a t v a r i o u s t i n e up t o 9 weeks a f t e r implanta t ion . The s t i m u l a t i o n was done o n l y when t h e s e p a r a m e t e r s w e r e m e a s u r e d 3.1nder a n e s t h e s i a . T h e m o n o p o l a r b i p h a s i c a l t e r n a t i v e b i d i r e c t i o n a l c u r r e n t (AEDZ) waveform was used for s t i m u l a t i o n . From 3 weeks a f t e r the i m p l a n t a t i o n , t h e i n t e r e l e c t r o d e impedance i n d i c a t e d s t a b i l i z e d va lue of 300 - 400 ohii. The t h r e s h o l d c u r r e n t w e r e 0.8 - 1.3 mA a t 9 wee!ts a f t e r implanta t ion . These va lue were smal I enoush f o r s t i m u l a t i o n of t h e nerve. The maximal evoked t i d a l volume were 26 - 29 ml/kg a t 9 weeks a f t e r i 3 p l a n t a t i o n . E f f e c t i v e c o n t r a c t i o n of diauhraogms w e r e o b s e r v e d for 9 weeks. Thouzh t h e e l e c t r o d e l e a d s w e r e p a s s e d t h r o u g h t h e c h e s t w a l l , t h e r e i s no c a s e of n e r v e i n f e c t i o n d u r i n g t h e s e e x p e r i n e n c s . U s i n g t h i s e l e c t r o d e , t h e o x f o l i a t i o n of t h e phrenic nerve i s not necessary and the nerves can be p a i n t a i n e d i n t a c t s t a t e and tho r i s k of t h e o p e r a t i o n can be minimized. l<irnura,?i++, Sugi ura,T."', Fukui ,Y.*, Togawa,l.t*, Harada,Y.*** *Grad. Sch. of E l e c t r . S c i . " ~ T e c ? . , **Res. I n s t . o f E l e c t r . , S h j z u o k a Univ. ++%-+'Ist Dept . of Surg . F ' a x m a t s u Univ. Sch. of i k d . , f iz ia inatsu, Japan

163 JXTERACTION OF BLOOD AND A I R I N VENOUS LIME A I R c u p CHAMBER

164

Contact of blood and a i r i n a d i a l y s i s r i r c u i t i s one of t h e non-physiological c o n d i t i o n s which could cause unfavorable e f f e c t s d u r i n g hemodialysis. We s t u d i e d t h e e f f e c t of b lood-a i r i n t e r a c - t f o n i n a vep.oTls l i n e a i r t r a p cbamber(V-chamber) on p l a t e l e t s and leucocytes .

l e v e l s i n t h e V-chamber. A t h igher blood l e v e l , Slood s u r f a r e w a s calm, but a t l o w e r l e v e l , t h e s u r f a c e was per turbed and bubbled. Prothrombin t ime(PT), a c t i v a t e d p a r t i a l th romboplas t in t ime (APTT) , f i b r i n o g e n ( f b e ) , ant i thrombid(ATI0 , plas- ainogen(p1g) and ct2-plasmin i n h i b i t o r (u2PI) were measured h e f o r e and a f t e r t h e d i a l y s e s . Thin lay- e r of middle chain t r iglycer ide(MCT) was f l o a t e d on t h e blood i n t h e V-chamber i n o r d e r t o s e p a r a t e blood and a i r . and t h e n PT,APTT,fbg,ATB,plg,aZPT, p l a t e l e t aggregation,PF4 and BTG w e r e a l s o mpasur- Ed. I n v i t r o , f r e s h blood w a s incubated i n revo- l u t i n g loops according t o t h e Chandler ' s method w i t h o r without a i r , and PT.APTT,fbg,ATJand p l g were measured and blood cells w e r e counted. Leucocytes decreased when t h e blood l e v e l i n t h e V-chamber was lowered. P l a t e l e t aggrega t ion wi th ADP increased a f t e r p a s s i n g through t h e chamber and t h i s i n c r e a s e was prevented by MCT. In v i t r o , p l a t e l e t s more decreased when blood v a s revolu ted w i t h a i r t h a n without a i r .

Blood and a i r c o n t a c t i n t h e V-chamber decreased leucocyte and increased p l a t e l e t s a g g r e g a b i l i t y . These changes may cause unfavorable e f f e c t s t o t h e p a t i e n t s and l e a d t o s e v e r a l compl ica t ions accom- anyi in^ l o n g term hemodialysis t rea tments .

Dia lyses were performed under 2 d i f f e r e n t blood

- . Y L + =u o r i i K i t m t p , Shigeru Kiyama il b" iko Ikezaki , Mahito Nakayama'and Tatsuo k a b TRe 3rd Department of I n t e r n a l Medicine, Kumamoto

Masao Tomi a

Univers i ty Medical School , Kumamoto, Japan

To e l u c i d a t e t h e i n f l u e n c e s on improvement i n anemia wi th r-HuEPO(EP0) on hemodialysis ( H D ) e f f i - c i e n c i e s and procedures , 62 HD p a t i e n t s under EPO t rea tment were s u b j e c t e d . Reduct ion r a t e ( R R ) s of s m a l l molecular substances(BUN, C r , UA, K and P ) , plasma and whole blood v i s c o s i t y , t h e degree of blood c l o t t i n g i n e x t r a c o r p o r e a l c i r c u i t and t h e changes i n HD procedures were r e t r o s p e c t i v e l y eva- l u a t e d a t t h e t w o p o i n t s , i . e . , b e f o r e and a f t e r EPO t r e a t m e n t , whend H t r eached t o 10%. Af te r EPO t r e a t m e n t , mean H t v a l u e rose from 18.6% to 30.8%, and concomitant i n c r e a s e i n p l a t e l e t counts was observed. Whole blood v i s c o s i t y i n c r e a s e d s i g n i f i - c a n t l y a long w i t h t h e r i se i n H t . S i g n i f i c a n t reduc t ion i n RRs of C r and UA a f t e r EPO t rea tment requi red i n c r e a s e i n blood flow r a t e and/or membrane s u r f a c e a r e a of d i a l y z e r , and pro longat ion of HD d u r a t i o n i n about 10% of t h e p a t i e n t s . S i m i l a r l y , dosage of P-binder i n c r e a s e d i n 7 pa- t i e n t s because of decreased RR and t h e r i s e i n a p p e t i t e . Hyperkalemic tendency was a l s o n o t i c e d , and 7 p a t i e n t s r e q u i r e d K-exchange r e s i n o r l o w K d i a l y s a t e . I n c r e a s i n g r e s i d u a l b lood i n d i a l y z e r l e d t o t h e increment of h e p a r i n dosage and t h e use of a n t i - p l a t e l e t drug i n 7 and 2 c a s e s , r e s p e c t i v e l y .

I t is concluded t h a t c o r r e c t i o n of anemia w i t h EPO provides s e v e r a l d i sadvantages on HD e f f i c i e n - c i e s and a n t i c o a g u l a t i o n , however, these problems can be e a s i l y overcome by convent iona l HD techniques and adequate medica t ions . Er iko Kinugasa, Fumiyoshi Nakayama, Tadao Akizawa, Shozo Koshikawa Fuj igaoka H o s p i t a l , Showa U n i v e r s i t y Yokohama, Japan

THE EE35CT OF PLASMAPHERESIS ON PLASMA VISCOSITY

The effects of double f i l t ra t ion plasmapheresis(DFPP) and cryofiltration to change the plasm viscosity w e r e studied, and the factors in plasma which influent t o the plasm viscosity w e r e investigated.

Materials and methcds:three cases of cryo- g lobur inha and three cases of hyperlipidemia were studied. Evaflux-5A(membrene porz size: 300; thickness:40pm) as the 2nd filter were used for DFPP and cryofiltrztion. Plasma viscosity was mnib red durig the therapy, and the peripheral b l d f l m of pre/post plasmpheresis w e r e evaluated by thermography. Futhernwre, the relation between plasma proteins and the plasm viscosity was investigated in these cases.

the DFPP and cryofiltra.tion therapies. Clinically, subjective and objective symptoms were +roved and peripheral w r a t u r e were increased according to the inprovemat of peripheral blood flow in c rycq loburhka cases. The peripheral blood flm w e r e also *roved according to the decrease of plasma viscosity i n h p r - l i p i d h a cases. And we found that the concentration oft-doburin and fibrinogen were the i q - ortant factors influent to the plasma viscosity, in these cases.

f i l traion were the effective therapies to decrease the plasm viscosity.

M.Kitamura, M.Hida, S.Hiraga, T.Satoh

wpt . of Transplantation I, School of redicine Tokai University

Fesults:Plasm viscosity was decreased during

In conclusion, we found that DFF'P and cryo-



165

167

AORTIC VALVE RING m G E M E N T WITH LEFP ANTERIOR

PROFILE BILEAFLE2 VALVE

St. Jude Medical prosthesis are used for various procedures of cardiovascular surgery. surgical procedure of aortic valve ring enlargement by the incision of left anterior fibrous trigone(W) and usefulness of bileaflet-type prosthesis for this procedure wre studied in 8 mnyrel dogs. A transverse aortic incision was mde into the camissure between left and right coronary cuspids. Aortic valve was resected and the size of aortic valve rinq was measured. %le aortic incision was longitudinally ehtended into IAET. A fusiform Xenomdica patch was sewn with continuous sutures into the LAFT incision and into the aortic rmt. After this enlarga.?ent, the aortic valve ring was 10% or more larger than the original size. The low profile bileaflet valve could be a prosthesis of choice for this procedure of aortic valve ring enlargement because of its syimetric orientation of leaflets and larger efPective valve orifice area.

FIBROUS TRIGONE INCISION: USEFULNESS OF Low

Recently, l o w profile bileaflet valves like

A new

Massya Xitamura, Masahiro hdo, Akimasa Hashimoto, Hitoshi Koyanagi Dept. of Cardiovascular Surgery, H& Institute of Japan, 'Ibkyo Women's Mxiical College,Tokyo,Japan

BIOCOMPATIB IL ITY ASPECTS OF A I E Y CELLULOSE- TRIACETATE ( C T A ) OIALYZER

S i e v i n g c o e f f i c e n t s (SC) o f IOU m o l e c u l a r n e i g h t p r o t e i n s ( b e t a - 2 - m i c r o g l o b u l i n (b211). m y o g l o b i n (myo) . rctinol-binding-protein, a c i d a l p h a - 1 - g l y c a p r o t e i n . a l p h a - 1 - a n t i t r y p s i n . p r e a l b u m i n , a l b u m i n ) a n d e f f e c t s o n u h i t e b l o o d c e l l s (Y8C) a n d c o m p l e m e n t c o m p o n e n t C3a n e r e t e s t e d u s i n g a C T A membrane ( C T 1 1 0 a n d CT190. B a x t e r , U S A ) . P l a s m a l e v e l s o f 8211 (11.8 kD) d e c r e a s e d s i g n i f i c a n t l y d u r i n g 3 h o u r s f r o m 38;6+-1.8 t o 24.5+-1.9 m g / l . p<O.OOl ( C T 1 1 0 ) a n d f r o m 32.2+-5.6 t o 16.1+-3.1 m g / l , p < O . O 2 5 (CT l e 0 ) . l l y o (17.2 kD) d e c r e a s e d f r o m 166.4+- 19.2 t o 114.4+-12.2 n g l m l n i t h C T 110. The p r o t e i n s n i t h a h i g h e r m o l e c u l a r n e i g h t d i d n o t c h a n g e s i g n i f i c a n t l y . T o t a l r e m o v a l o f b211 n a s 120 mg and o f m y o 1.1 19 ( p e r 1' membrane s u r f a c e a r e a / 3 h o u r s d i a l y s i s ) . S C f o r b2H a n d myo u a s a b o u t 0.6. F o r t h e o t h e r p r o t e i n s t h e membrane n a s n e a r l y i m p e r m a b l e ; YBC d e c r e a s r a f r o m 5.0+-0.55 t o 4 . 5 6 + - 0 ; 4 6 c e l l s l n l ( C T 1 1 0 ) a n d f r o m 7.00+-0.50 t o 4.85+-0;67 c e l l s l n l (CT 190) . Y i t h i n t h e f i r s t 5 ' C3a i n c r e a s e d n i t h CT 1 1 0 f r o m 307+-73 t o 6 5 4 + - 1 9 8 n g / m l ( a f f e r e n t ) a n d f r o m C55+-155 t o 1 0 7 8 + - 2 4 4 n g / m l ( e f f e r e n t ) . W i t h C T 1 9 0 C3a i n c r e a s e d f r o m 3 7 9 + - 3 0 t o 950+-163 n g / m l ( a f f e r e n t ) a n d f r o m 1 7 4 3 + - 5 8 3 t o 3371+-553 n g l m l ( e f f e r e n t ) . Con- c e r n i n g p e r m e a b i l i t y , d e g r e e o f l e u k o p e s i a a n d c o m p l e m e n t a c t i v a t i o n t h e membrane seems t o b e c o m p a r a b l e t o t h e p o l y s u l f o n e membrane.

K l i n k e B. R l l c k e l A . A b d e l h a m i d S. F i e g e l P. Y a l b D: O e u t t c h e K l i n i k f i r O i a g n o r t i k , A u k a m n a l l e e 33. 0-6200 Y i e s b a d e n . Yes t -Germany

166

168

DESIGN OF A FUZZY LOGIC-BASED SUPPORT SYSTEM FOR ARTI- FICIAL HEART CONTROL

This study represents a design method of a fuzzy logic-based intelligent system to support decision making for artificial heart control. The system provides diagnostic information and control laws to the controlling variables, pump outputs and dose frequencies, for keeping the circulatory system physiologic.

three groups of fuzzy rule: (1) t o determine laws to the controlling variables on empirical knowledge, (2) to select a proper level of circulatory system models necessary for diagnostic suggestions depending on the circulatory conditions and run the model, (3) to determine laws to the controlling variables interpreting the analytical results in (2 ) . An engineering work station involving parallel two

CPU's is used. The one is for fuzzy inference, and the other solves a selected circulatory model with on- and off -line data obtained from the circulatory system. The use of the fuzzy logic is effective to represent

knowledge f o r the designed support system because there is much indefinite domain knowledge in the rapidly evolving field of artificial heart control. More- over, the on-line computer simulation with circulatory system models enhances the capability of the system. This is because the obscurity inherent in the medical knowledge can be clarified by the analytical reasoning by the mathematical models.

Tadashi Kitanura: Kyushu Institute of Technology, Japan Pumio Iwaya: Fukushima Medical College,Japan

The knowledge base of the support system consists of

ROLE OF HEPATO-COLONIC UREA RECYCLING IN THE HYPERAMMONEMIA OF UREMIA

A hepato-enteric cycle for urea exists in most manrmals whereby urea secreted into the GI tract is metabolized to ammonia by bacterial and enteric ureases. Ammonia enters the portal circulation and is utilized in the hepatic synthesis o f urea. In the absence of renal excretion, enteric secretion of urea may be increased. The present study aimed to determine whether amplification of this hepato-enteric urea cycle is responsible for the hyperammonemia observed in uremia. Sprague-Dawley rats were distributed in three groups: a sham group, a group that underwent bilateral nephrectomy (Nx) and a nephrectomy group with urea loading by o r a l gavage. Animals were sacrificed 48 h after surgery and blood collected f o r measurement of creatinine and BUN (in mg/dl) and ammonia (in uM). (*p<O.Ol vs sham) (tp<O.Ol vs Nx)

Group (N) Creatinine BUN Ammonia Sham (6) 0.45+0.03 21+3 30+2 Nx ( 8 ) 7.59+0.34* 241+13* 56+7* Nx+urea (7) 5.35:0.25* 338{16*t 14i~21*t Urea loading led to an accentuation of the hyperammonemia that was observed with nephrectomy. Furthermore, we found a significant correlation between ammonia levels and BUN in the total groups (rs0.83, p<O.Ol), These results suggest that increased enteric urea secretion contributes to the hyperammonemia observed in the uremic syndrome. Jens Klinkmann, Peter Ivanovich and Mujais, VA Lakeside and Northwestern University, Chicago, IL, USA and Wilhelm-Pieck-Universitat, DDR-2500 Rostock.

Arfificial Organs, Vol. 13, No. 4, 1989


169 DEVELOPING AN OPTIMAL POSITION FEEDBACK CONTROLLER THAT MINIMIZES THE ELECTRIC ENERGY CONSUMPTION OF THE EVAD

An electric ventricular assist device (EVAD) converts electric power into blood flow by moving a pusher plate against a flexible blood sac. This paper addresses the development of an optimal, position feedback, pusher plate controller. The controller minimizes the electric energy consumption of the EVAD, and consequently reduces the size of the required battery pack.

The control law formulation utilizes the measured pusher plate position as the only feedback signal. It incorporates statistical information o f the targeted patient population, and optimizes the expected value of the EVADs performance. It is shown that a time shift manipulation of the feedback gain functions can drive the W A D at various speeds. This technique is used for adjusting the EVADs beat rate to meet the body's cardiac output demand.

Mock loop tests of the optimal pusher plate controller were conducted at blood flow rates of 5, 8, and 9 [l/min], and initial aortic pressure of 80 [mmHg]. The energy savings in these tests were 0.8 @I%), 0.35 (SYo), and 0.79 (1 8%) [Joules/cycle], correspondingly, when the performance of the optimal controller was compared with the performance of the current velocity controller. Furthermore, the optimal pusher plate controller reduces the motor's peak power from 35 to 15 [Watts]. This peak power reduction will ease the design o f the transcutaneous energy transmission circuits.

Glenn K. Klute, Uri Tsach, David B. Geselowitz The Bioengineering Program and The Department of Mechanical Engineering, The Pennsylvania State University University Park, PA 16802, U.S.A.

171 P N ~ ~ ~ ~ ~ r ~ ~ ZATIOI.T O F .S,F.iALL DIA",iETER G R W T S OF LONG FICRITdS

A n i d e a l s u b s i t u t e , i n $ a r t i c u l a r f o r small diameter a r t e r i e s , i s n o t

b y a n a t i v e ves se l t i s s u e a f t e r l o n g i m p l a n t a t i o n . W e h a v e r e v e a l e d t h a t s m a l l l i a m e t e r g r a f t n e e d s v e r y p o r o u s s t r u c t u r e c o a t e d w i t h b i o d e g r a d a b l e a n d a n t i t h r o m b o g e n i c m a t e r i a l s t o e n s u r e s t a b l e e n d o t h e l i a l l i n i n g o n t h e s u r f a c e . Ex,>anded g o l y t e t r a f l u o r o e t h y l e n e (EPTFE) i s h i g h l y i n e r t a n d has b e e n u s e d f o r a r t i f i c i a l g r a f t . B u t , t h e c o m m e r c i a l l y a v a i l a b l e g r a f t s of f i b r i l l e n g t h 2 0 - 3 0 m i c r o n , do n o t provide good c e l l a n d t i s s u e i n g r o w t h among f i b r i l s . a f i b r i l l e n g t h of a S o u t 1 0 0 m i c r o n a n d t h i n w a l l e d g r a f t , of w h i c h t h e i n n e r s u r f a c e is coated w i t h c o l l a g e n - h e p a r i n c o m > l e x . Coated and n o n c o a t e d g r a f t s w e r e i m ? l a n t e d i n t o r a t a b d o n l i n a l aor ta . T n e c o a t e d g r a f t s s h o w e d good n e o i n t i m a g r o w t h a n d e n d o t h e l i z a t i o n . On t h e c o n t r a r y , t h e n o n c o a t e d g r a f t s s h o w e d W O r h e a l i n g process a n d n e o i n t i m a g r o w t h . T h e s e r e s u l t s s u g g e s t e d t h a t a n i n i t i a l 2:Lasma ? r o t e i n l a y e r f o r m e d o n t h e s u r f a c e 0:: t h e g r a f t a t i m p l a n t a t i o n i s i m $ o r t a n t t o i n d u c e s t a b l e n e o i n t i m a g r a o w t h b e c a u s e c o l l a g e n - h e p a r i n l a y e r w o u l d be & T r a d e d wi.t:hin o n e m o n t h .

~t i s t h o u g h t t o be replaced

W e select

Makoto Kodama R e s e a r c h I n s t i t u t e for P o l y m e r s a n d T e x t i l e s T s u k u b a , Ibaralci , J a p a n

170 ASSIST CIRCULATION BY RETROGRADE CARDIO- SYNCHRONOUS PERFUSION O F CORONARY SINUS

I n our l o n g s u r v i v a l exper iments on 4 G dogs and c a l v e s w i t h induced a c u t e h e a r t f a i l u r e i t w a s s t u d i e d t h e i n f l u e n c e of a s s i s t c i r c u l a t i o n by r e t r o g r a d e ca rd io - synchronous p e r f u s i o n (RCP) of coronary sinus on t h e b i o e n e r g e t i c s , metabolism and f u n c t i o n of i s chemica ly i n j u r i e d myocardium. The RCP method was f i r s t r e p o r t - ed by t h e a u t h o r s a t t h e h I n t e r n a t i o n a l Congress of Hear t S tudy S o c i e t y i n 1980 and a t t h e I X World Congress of' Card io lo- g i s t s i n 1982 i n Noscow. S ince t h a t t h e a u t h o r s improve6 t h e t e c h n i c a l means f o r RCP and s t u d i e d i t i n combination w i t h d e f i b r i l l a t o r , ba l loon assist, o r v a r i a - t i o n i n l e f t a t r i a l p re load and unload.

The RCP a p p l i c a t i o n i n o w exper iments improved t h e cardiodynamics, t h e e l e c t r o - l i t e end ac id-base ba l ance , and r e s t o r e d t h e l a c t a t e / p y r u v a t e r e l a t i o n , t i s s u e enzyme a c t i v i t y and AT'P c o n t e n t i n myocardium. A l l ou r b iochemica l and ECG r e s u l t s were proved by t h e e p i c a r d i a l maping by Maroko and by morphometrical s t u d i e s , which a l s o r e v e a l e d the r e d u c t i o n o f is- chemical a r e a s i n myocardium.

The RCP method w a s s u c c e s s f u l l y a p p l i e d i n two p a t i e n t s w i t h a c u t e myocardial i n - i a r c t i o n , h e a r t fa i lure and u n s t a b l e s t e - nocard ia .

Leonid F. Koblov, V l a d i m i r E. Tolpekin , Arkady Ia. Kormer, Ga l ina K. T jun ina I n s t . of T ransp lan to logy & A r t i f i c i a l Organs, l i n i s t r y o f Hea l th , Moscow, USSR.

172 LASER ANGIOPLASTY FOR AV FISTULAS I N PATIENTS WITH CHRONIC HEMODIALYSIS

One of t h e major problems with chronic hernodialysis i s s t e n o s i s or occlus ion i n an a r t e r i o v e n o u s f i s t u l a . Recent ly , percutaneous t rans luminal ba l loon a n g i o p l a s t y (PTA) has become ,accepted as e f f i c i e n t therapy f o r a s t e n o t i c l e s i o n i n an AV f i s t u l a . However, PTA i s not s u c c e s s f u l f o r a long segmental complete occ lus ion o r hard s t e n o s i s . Furthermore, we need t o approach t;ie problems of r e s t e n o s i s i n chronic p a t i e n t s . Accordingly, we have eva lua ted percutaneous t rans luminal l a s e r a n g i o p l a s t y (PTLA) i n 9 cases of chronic hernodialysis. We int,rorluca.' 7 - 0 F r shea th i n t o t h e AV f i s t u l a and observed i n s i d e t h e shunt by angioscopy. And then , we used an SLT Nd-YAG Laser c o n t a c t method (probe d iameter ; 1.8 - 2.2 .nr) f o r PTLA. Subsequent ly a f t e r PTLA, we performed PTA. I n t h e 3 p a t i e n t s p r e s e n t i n g completely- s tenosed lesions, we obtained s u c c e s s f u l d i l a t a t i o n . I n t h e o t h e r 6 CRGPS wi th s t e n o t i c l e s i o n s , we vaporizec! a l l abnormal c o n s t r i c t u r e s . For cases i n which PTA a lone cannot o b t a i n s u c c e s s f u l blood f l o w , we can r e s t o r e blood flow i n t h e AV f i s t u l a by apply ing PTLA.

Nobuhiko KoRa, Takashi S a t o , S h i n j i Uchiyama, Koji Kohchi, Koga Hospi ta l , Kurume Ci ty , Japan

Artificial Organs, Vol. 13, No . 4, 1989

326 ABSTRACTS OF THE VIIih WORLD CONGRESS

173 A NEW TKILAYEK AH'I'IFICIAL SKIN CIIMI'OSEII [IF ('OLI.AGEN MATRIX

Recent ly we have Iwen Lound i h . i i t l i e c.01 l ag r~ i ious i i ia ter i . i l cmposed of FiLrill~ir i w l l agen a n d the lieat dcnaturt:d collagen w I tli 1 he Iiydrothci. ina1 c r o s s l i n k i n g wd- t.rniisf igui-tad t o t l l v t o ~ ~ l i e ~ - l i v e tissue of the pseudoderiiiis--~ike w i l l i i n a veek i n su1)ciitaneiJus implantat i on iniodel o f i.;itn.

111 this study, whcn col lagr l l - - l lased dress inx w a s g r a f t e d onto full - t h i c l m e s s excised dermal w ~ ~ a n d s on t h e Imck o f r a l s . t he l i i s t o l ~ ~ n i r a l s t u d y showed a1 t l ie v a r i o u s stage5 of IWUIII-1 heal inx . A UPIV I r i - layer a r t i f i c i a l skin w a s ~cmposrd nf Imttl-)in layer of. t Iir f ibri I lar crr1 lagen and t h y h e a t dc.natrired cell I agen(FC-ItAC) w i t h the dehydrothermii l cross- I j i i b i n g and the cPn t raL 1ayc.r of t h e fil~rill~ii~ CI I 1 1 a gen ( FC ) w i t h t 11 e 1-1 iein i CR 1 cross 1 i n k i 11 g and the upper l a y e r of 3 silicon elastomer.

:iyl)eared of t h e .;t r n c t u r r of s i~oi ige s t a t e . 3 n d he- i'amc! a colloIdol s ta t ( ! . 7 days a f t e r g ra f t inz . f i - b rOlJ las t s were 0lJservt:d a t t h e graft-normal d e r m i s ~~oundnl~y, f i b r o h l d s t s and nt 'ut rophi 1s m i g r r n t Pd at t he c e n t r a l p a r t . O n t.he o t h e r hand. regenerated ep ide rma l shee t m i g r a t e d f'roin the wound rrlzti jus t a s d e v i d c d Iwtweeii FC-HA(: and FC layer.

4 and 7 weeks after g r a f t i n g , f i b i - c h l a s t s and c a p i l l a r i e s infiltrated t:vently <]lid a newly ( '011-

n e c t i v e t i s s u e which composed of a f ~ ) l d anrl wide c o l l a g e n f i h e r was formed w i t h inter5titIal A healed epidermal was c:ovt:red the w o u n d w h i l e and the epidermal ridge was observr :d , f u r l hcrinorr: I lle p r e s e n c e of' basement membrane was o)nf i ri11cd from elect roil micrograph and histological study

1 day a f l e r g r a f t i n g , FC--1IAC l a y r r .aIre~dy di.i

Flikio Koide, Krn--ichi Osalti ' T ~ d ~ n i c ; ~ l 1MD LIivision,Tc.rrin~o CO. ,Fuj i , Shizrioka,

175 L IP ID AND BLOOD RHEOLOGY I N PATIENTS W1TH FAMILIAL HYPERCHJLESTEROLEMIA (FH) U S I N G LOVASTA- T I N ALONE OR IN COMBINATION WITH LDL-APtERESIS

The hypo l i p idemic agent l o v a s t a t i n (Merck Sharp & Dohme), 40 mg d a i l y , was used t o t r e a t 20 p a t i - e n t s ( 1 1 males and 9 females) aged 32-60 years w i t h heterozygous FH. I n 10 p a t i e n t s (Group 1 ) on c h o l e s t e r o l - l o w e r i n g d i e t s f o r 3 months, l o v a s t a - t i n was found t o decrease c h o l e s t e r o l (C) and tri- g l y c e r i d e (Tg ) l e v e l s by an average o f 30 and 16%, r e s p e c t i v e l y , and inc reased h i g h d e n s i t y l i p o p r o - t e i n s (HDL) by 14% (p < 0.05) . I n a d d i t i o n , asymp- t o m a t i c b lood v i s c o s i t y ( n ) and l o w shear v i s c o - s i t y ( n ) were a l s o i n c r e a l e d by 12.08+5.06 and 32.4t9.68, r e s p e c t i v e l y ( p < 0 .05) , y i e l d s t r e s s (To) , by 52.0+17.5% ( p < 3 .05) , even though hema- t o c r i t ( H ) was decreased by 10.34+2.77% ( p < C.01). Changes i n plasma v i s c o s i t y ( n ) were i n s i g n i f i -

I n l G p a t i e n t s (Group 2 ) who underwent LDL- apheres i s , a 3-month use o f l o v a s t a t i n caused an a d d i t i o n a l r e d u c t i o n i n C and Tg l e v e l s by 25 and 14%, r e s p e c t i v e l y , and a 8% inc rease i n HDL ( p < 0.01), whereas n , n , and H were i n s i g n i f i c a n t l y changed ( p > 0.04). PAL-apheresis a p p l i e d a long w i t h l o v a s t a t i n the rapy s i g n i f i c a n t l y improves b l o o d rheo logy and c h o l e s t e r o l - l o w e r i n g e f f e c t s i n p a t i e n t s w i t h FH.

cant . P l

G. Konovalov, N. M ikha i l ova , A. Rogoza, 0. Atkov, V. Kukharchuk A l l - L h i o n Card io logy Research Center, USSR Academy of Medica l Sciences, Moscow, USSR

174 CFXYGES IN PLASMA LEVELS OF ATRIAL NATRIURETIC PEPTIDE DURING PLASMAPHERFSIS

Plasma levels of atrial natriuretic peptide(ANP) decrease during hemodialysis, caused by drastic hemodynamic changes, but there have been few reports concerning plasma ANP levels during plasmapheresis. Plasma AWP levels were measured sequentially during plasmapheresis in 6 patients with familial hypercholesterolemia. This treatment was performed with a double membrane filtration (m 8500, Kuraray) o r a selective LDI. aheresis method using dextran-sulfate cellulose columns(Kapeka). Plasma ANP levels at the time of 0.2, 1, 2, apd 3 liter plasma treatment were, respectively, 26.2215.6 (Mean+SD) pg/ml, 22.056.5, 25.3211.0, and 23.4211.8. There were no apprecjable changes in plasma ANP levels throughout the treatment. This finding differs from the results obtained with hemodialysis, and supports the view that the hemodynamics during plasmapheresis i s stable. In addition, ANP and arginine vasopressin levels were also measured in plasma passed through the dextran-sulfate cellulose column. ANP levels significantly decreased, while vasopressin levels did not change by passing the column. These results suggest that the dextran-sulfate column has the different affinity f o r peptide hormones according to their classes. Shunichi Kojima, Mariko Harada, Shuichi Nomura, Morio Kuramochi, Akira Yamamoto. Terun Omae National Cariovascular Center

176 A TOTAL ARTIFICIAL HEART (T4H) FOR NEONATES A I l D INFAI ITS AS A BRIDGE TO TRANSPLAN- T4T I ON.

T r a n s p l a n t a t i o n o f neonata l h e a r t s has been i n i t i a t e d . The y e a r l y number o f h e a r t t r a n s p l a n - t a t i o n s i n neonates and i n f a n t s i s expected t o be a p p r o x i m a t e l y 3,000 f o r N o r t h America. O f t hese neonates and i n f a n t s , some w i l l need a TAH as a b r i d q e t o t r a n s p l a n t a t i o n .

A p n e u m a t i c a l l y d r i v e n TAH was des iqned t o f i t t h e p e r i c a r d i a l c a v i t y o f a neonate. F i t t r i a l s i n cadavers have shown t h a t t h e o u t e r dimensions conform t o t h e anatomy o f t h e ches t . I n f l o w and o u t f l o w t r a c t s a r e i n accep tab le a l i gnmen t w i t h normal anatomy o f a t r i a , pulmonary a r t e r y and a o r t a . A 6 m l s t r o k e volume w i l l , w i t h a h e a r t r a t e o f 100-120 bpm, g i v e adequate c a r d i a c o u t p u t . The s i z e o f i n f l o w v a l v e s i s 12.Dmm O.D. and 9.0mm O.D. f o r t h e o u t f l o w v a l v e s .

A l l p a r t s , i n c l u d i n g t h e t r i l e a f l e t va l ves a r e made by vacuum f o r m i n g . Double lumen t u b i n g serves b o t h v e n t r i c l e s .

The t e s t i n g p r o t o c o l f o r t h i s new TAH and r e s u l t s w i l l be presented. D u r a b i l i t y t e s t i n g i s c u r r e n t l y t a k i n g p l a c e showing p r o m i s i n g r e s u l t s . To p rove r e l i a b i l i t y under c o n t r o l l e d c o n d i t i o n s , t h e cascade i n f a n t mock c i r c u l a t o r y system w i l l be used. I n v i t r o exper iments w i l l be per formed t o measure hemolys is and i d e n t i f y p r e d i l e c t i o n s i t e s f o r thrombus f o r m a t i o n . I m p l a n t a t i o n i n an imal model i s a n t i c i p a t e d .

The m a t e r i a l used was po lyu re thane ( P e l l e t h a n e ) .

E Kopper t ; N B ishop; P Swier; M Ochs; S Topaz; J v Griensven: LS Yu; B Yuan; WJ K o l f f . Dept . of Surgery, Univ . o f Utah, S a l t Lake, Utah

USA


ABSTRACTS OF THE VIIth WORLD CONGRESS 32 7

177 FEMORAL STRAIGHT PTFE GRAFT AS ALTERNATIVE BLOOD ACCESS FOR HEMODIALYSIS

Blood a c c e s s w a s c r e a t e d u s i n g a t a p e r e d expanded PTFE g r a f t a t t h e t h i g h o f t h e f i v e hemodialyzed p a t i e n t s f o r whom it w a s imposs ib le t o make an i n t e r n a l s h u n t a t t h e upper e x t e r m i t y and an app- r o p r i a t e saphenous v e i n g r a f t was n o t a v a i l a b l e .

One end of t h e g r a f t wi th a d iameter of 5 mm w 1 3 s anastornosed t o t h e p o p l i t e a l a r t e r y i n end-to- s i d e f a s h i o n , t h e g r a f t was p l a c e d i n t h e subcutaneous t u n n e l and then t h e o t h e r end of 7 mm i n d i - ameter was anastornosed t o t h e g r e a t e r saphenous v e i n i n end-to-s ide f a s h i o n i n four cases and t o t h e femoral v e i n i n one c a s e .

eti two weeks after g r a f t i n g . There were f o u r e p i - sodes o f th rombot ic o c c l u s i o n b u t t h e g r a f t was e a s i l y thrombectomized wi th a Forgaty c a t h e t e r . G!-aft i n f e c t i o n and aneurysm format ion was noted i n one c a s e , r e s p e c t i v e l y . The g r a f t remained p a t e n t f o r more than 18 months i n t h r e e o f t h e f i v e p a t i e n t s . The b lood flow through t h e g r a f t measured by t h e u l t r a s o n i c duplex system was ai-ound 500 ml/rnin.

I t w a s concluded t h a t a s t r a i g h t PTFE g r a f t a t t h e t h i g h is more e a s i l y thrombectomized as compa- r e d t o a loop g r a f t and t h a t i t should be an app- r o p r i a t e a l t e r n a t i v e b lood a c c e s s .

G r a f t puncture and hemodia lys i s could be start-

Kazuyoshi Kubota, Akih i ro Kawauchi, Hideo Ohta, Ycshih isa Chiba, Aki ra Inoue, Tadashi Koike. Cepartment of Surgery , Showa. U n i v e r s i t y , School c f Medicine

179 SIMPLER METHOD OF ASSESSING FREE HEMOGLOBIN AND HAPTOGLOBIN TREATMENT FOR HEMOGLOBINEMIA C O M B I N E D WITH LONGTIME EXTRACOAPORAL C I R C U L A T I O N

Hemoglobinemia by mechanical hemolysis was found i n t h e c a s e s under longt ime e x t r a c o r p o r a l c L r c u l a t i o n w i t h c a r d i a c s u r g e r y . For t h e t r e a t - ment of hemoglobinemia i t was n e c e s s a r y t h a t q u a n t i t a t i v e a n a l y s i s of f r e e hemoglobin was per- fermed r a p i d l y and s imply .

This column method was s i m p l i f f i e d measurement by means of sepharose immobil ized haptoglobin . This method w a s e v a l u a t e d i n 20 p a t i e n t s (9 v a l v e r t p l a c e m e n t , 2 v a l v e p l a s t y and 9 CABG) under longt ime e x t r a c o r p o r a l c i r c u l a t i o n and compared wi th o r d i n a r y method. I n r e s u l t s , f r e e plasma hemoglobin was 49.1?31.4mg/dl by column method and 42.6+29.2mg/dl by o r d i n a r y method respec- t i v e l y . T h e r e s u l t s showed t h a t t h i s column method was u s e f u l measurement of f r e e hemoglobin a s w e l l a s o r d i n a r y method. The o t h e r hand,we used t h e haptoglobin i n j e c t i o n (Green-Cross) f o r t h e t r e a t m e n t and t h e preven- t i o n of hemoglobinemia a f t e r e x t r a c o r p o r a l c i r c u - l a t i o n . Haptoglobin (4000u.) was used beforehand i n t h e pr iming s o l u t i o n of e x t r a c o r p o r a l c i r c u - l a t i o n .

Free plasma hemoglobin a t t h e end s t a g e of e x t r a c o r p o r a l c i r c u l a t i o n was Omg i n haptoglobin t r e a t e d group and 3b.0?25mg/dl i n no t r e a t e d g-roup. The r e s u l t s s u g g e s t t h a t haptoglobin in . iec t ion was e f f e c t i v e drug f o r p r e v e n t i n g of menhanical hemolysis .

Ta’:suhiko Kudo, Tsuyoshi Shimizu, Naoki Konagai, Te-:suya Osada, Yuriko I s h i i , Takeshi Tatsuta’i H x h i o j i Medical Center of Tokyo Medical Col lege . g< ‘The Green Cross Corpora t ion .

-

178 EFFECTIVENESS AND LIMITATION OF LVAD FOR TREAT- MENT OF PROFOUND PUMPING FAILURE

(LVAD) w e r e s t u d i e d exper imenta l ly i n swines w i t h c a r d i o g e n i c shock due t o a c u t e myocard ia l i n f a r c - t i o n (&!I). Hemodynamics, EVR, LV max d p / d t , T T I and PVR were p r e c i s e l y e v a l u a t e d i n e a r l y s t a g e a f t e r t h e i n i t i a t i o n of t h e LVAD. Twenty-one swines were used i n t h i s exper imenta l s t u d y and AM1 w a s made by means of m u l t i p l e l i g a t i o n s of t h e coronary arteries. V e n t r i c u l a r f i b r i l a t i o n occurred i n 11 o u t of 21 swines a f t e r p r o d u c t i o n of AM1 and mean p e r c e n t a g e o f t h e i n f a r c t e d a r e a of LV f r e e w a l l by means of NBT s t a i n i n g w a s 63%. By a p p l i c a t i o n of LVAD f o r t h e profound f a i l i n g h e a r t , a s i g n i f i c a n t d e c r e a s e of LV max d p / d t and T T I and a marked i n c r e a s e of EVR w e r e observed . Bes ides a d iminished l e f t v e n t r i c u l a r pre load and a f t e r l o a d , a d e c r e a s e of t h e c a r d i a c work and a n i n c r e a s e of t h e coronary blood f low could be o b t a i n e d . During LVAD a s a t i s f a c t o r y sys temic c i r c u l a t i o n s s u p p o r t could be main ta ined i n a o r t i c p r e s s u r e more than 90mmHg. However r i g h t c a r d i a c f u n c t i o n w a s n o t changed even by u t i l i z a t i o n of LVAD. The l i m i t a t i o n of t h e e f f e c t of l e f t v e n t r i c u l a r assist by only LVAD was i n about 1800 dyne s e c cm-5 from t h e view of pulmonary v a s c u l a r r e s i s t e n c e (PVR).

The e f f e c t s of l e f t v e n t r i c u l a r assist d e v i c e

Maki Kubota, Maseyoshi Okada, Masanao I m a i , Kazuo Nakamura 2nd Dept. o f Surg. , Kobe U n i v e r s i t y Medical School, 7-5-2, Kusunoki-cho, Chuoh-ku, Kobe, Japan

180 INCREASING THE INTERVAL BETWEEN LDL-APHERESIS PHOCEDLRES DUE TO LOVASTIN THERAPY I N PATIENTS WITH FAMILIAL HYPLRCKILESTEROLEMIA (FH)

Over 2-4 yea rs , LDL-apheresis was performed i n 10 p a t i e n t s (7 males and 3 fema les ) aged 33-57 y e a r s w i t h heterozyaous FH u s i n g a scheme.

Four p a t i e n t s had LDL immunoadsorption w i t h means o f columns c o n t a i n i n g p o l y c l o n a l a n t i b o d i e s , 3 p a t i e n t s , those c o n t a i n i n ? monoclonal a n t i b o - d i e s t o LDL, and ano the r 3 p a t i e n t s had LDL p l a s - ma a d s o r p t i o n w i t h columns c o n t a i n i n g h e p a r i n and sepharose.

I n t h e p a t i e n t s r e c e i v i n g c h o l e s t e r o l - l o w e r i n g d i e t s , a l ong - te rm a p p l i c a t i o n o f LDL-apheres is a t 7-14-day i n t e r v a l s r e s u l t e d i n an average 4C- 6C% decrease i n c h o l e s t e r o l (C) and LUL. Lovas ta - t i n (Merck Sharp & Dohme) g i v e n i n doses o f 20 t o 60 mg d u r i n g 6 months a d d i t i o n a l l y l owered C and LDL b y an average of 2 5 3 5 % and decreased C redu - c t i o n r a t e s a f t e r LDL-apheresis.

The a d d i t i o n a l t h e r a p e u t i c e f f e c t s enabled t h e i n t e r v a l between t h e LDL-apheresis procedures t o be i nc reased f rom 1 t o 2 weeks i n 3 p a t i e n t s and one p a t i e n t t o be t r e a t e d w i t h o n l y drugs.

V . Kukharchuk, C-. Konovalov, S. Pokrovsky, I. Adamova, E. Bokchubayev, E. Volkova A1 1 -Union Card io logy Research Center, USSR Academy o f Medical Sciences, Moscow, USSR

Artficial Organs, Vol. 13, No. 4, 1989


181 THE EFFICACY OF CRYOFILTRATION FOR IWLTIPLE ZYELOMA

conditions occur due to abnormal protein production. They are bleeding tendency, retinopathy, disturbance of central nervous system and so on. Therefore the removal of abnormal protein is important in addition to chemotherapy. We applied cryofiltration (CRYO) for the purpose of M-protein removal in 6 patients and fo r improvement of hyperviscosity in one patient. 4 1. of plasma is treated in one CRYO procedure. Average removal of total protein, IgG and IgA are 16.8%, 19% and 24% respectively. The blood viscosities are reduced to about 85% to 91%. In one case o f complicated renal failure, urine volume was increased from 0 ml/day to 1800 ml/day, and in another case Ccr was increased from 6 .5 l/day to 23.2 l/day. This is thought to be due to the consequence of microcir- culation improvement in the kidney. No complication due to M-protein is observed during the period of CRYO therapy.

and prophylaxis of the complications of multiple myeloma.

Kazutaka Kukita*, Jun-ichi MeguroX, iQotoki Yonekawa*, Akio Kawamura', Nobuhiko Abe", Kazutoshi Seto**, Naoki Kobayashi**, Tatsuro Irie **, Ken-ichi Kawamura**, Toshio Higa", Masaharu Kasaix*, Teizo Ariyama'**, Keiko Makita**** *Dept. of Surgery, "Dept. of Internal Medicine, Sapporo Hokuyu Hospital, Artificial Organ & Trans- plantation Hospital, Sapporo, ***2nd Dept. of Surgery, Asahikawa Medical College, Asahikawa, ****lst 3q:it. of Surgery, Hokkaido Univ., Sapporo, .ia?an

In multiple myeloma patients, various abnormal

In conclusion, CRY0 is effective to the therapy

182 A MECHANISM FOR AN RISE IN PLASMA BETA-Z-MICRO- GLOBULIN FOLLOWING HEMODIALYSIS.

According to our previous studies, an rise in plasma B2M following hemodialysis(HD) could not be explained merely by hemoconcentration or by enhanced synthesis of B2M or by enhanced release from circulating blood cells. This study was designed to clarify the mechanism for this rise of BZM during HD. P o s t HD plasma levels of BZM, myoglobin, and alpha-1-microglobulin were compared to predialysis levels, which were significantly increased by 7-17 % even if corrected for hemoconcentration. This may indicate that these rises in plasma levels are due to transitional shift of low molecular weight proteins(LMWPs) from interstitial sFace to intravascular space. To study the intercompartmental shift of LMwps dcring HI), in vitro experiment was done usig CAPD drainage fluid with or without 5 % albumin simulating intravascular and interstitial fluids passed through cuprophane membrane dialyzers. LMWPs were shifted from interstitial space to intravascular space concomitant with the movement of water. The concentrations of LMWPs were increased with inverse proportion to the reduction of extracellular fluid volume(ECFV). In conclusion, increased plasma level of B2M following HD is mainly due to the reduction of ECFV by fluid removal.

Kazuo Kumano, Masato Nanbu, Makoto Koyama, Shuichi Kusakari, Satoru Irie, Tadasu Sakai Kidney CenLer, Kitasato University Hospital Sagamihara, Kanagawa, Japan

183 The New Viennese Small TAH - Experimental a n d 184 Nd-YAG WEX AND U R E W i PREPOLyMER(UP) ADHESlM: First Clinical Experience FOR MICROENDONEURJAL ANASTOMOSIS

For bridging to transplantation, a new small TAH heart design has been developed. The two three layer membrane pumps (left: 87 cc; right 75cc; mechanical valves and screwed connectors) for orthotopic implantation have been used successfully in calf experiments. Pumping with a frequency of 117 f 2,4 beatdmin and with a cardiac output of 7.4 f 0,7 Umin, a survival of 180 days was reached without problems. On of March 1989 the New Viennese Small TAH was implanted into a 45 year old patient (height: 160 cm/ weight: 75 kg) suffering from an end stage coronary heart disease. The patient deteriorated (mean aortic pressure: 38 mmHg; cardiac output: 1,8 to 2,l Vmin; renal dysfunction; developing anuria and multiple organ failure) while waiting for a donor heart. Even though his pericardial space was very small no fitting problems appeared. Excellent fitting could be demonstrated by x-ray and oesophageal sonography, which showed no compression of the atrias by the ventricles. Additionally this sonographic method seems to be of important value for detecting thrombotic material in the atrias. By using a pumping frequency of 104,3 * 8,7 beats/min a cardiac output of 5,8 f 0,63 Umin was achieved. The plasma hemoglobin was 4,l f 0,48 mg/dl. Even though blood circulation was reestablished, after a TAH duration of 12 days, multiple organ failure persisted, renal function did not improve and due to infection TAH pumping had to be stopped.

Rokitansky A., Laczkovics A,. F'rodinger A., Schima H., Losert U., Wolner E. 2nd Surg. Dept. Univ. of Vienna

The aim of t h i s study was to t ry to find a rapid & simple method of nerve a n a s t m s i s . The experiments of end to end micr~endoneurial anastanosis were achieved by using a combination of Nd-YAG laser & Up adhesive on the 60 s c i a t i c ner-ves of SD rats . The results are showed below:

U s i n g a power setting of 10 watts & pulsed mode of 0.5 seconds on the laser, it was easy t o obtain good endoneurial anastomosis, without causing serious tissue damage; but the act ivity of anti- t e n s i l e strength was not included. The UP adhesive might s a t i s f y the object of maintaining the laser anastomosed nerve ends i n apposition unti l natural healing effects f irm union. The time required was about 5 minutes w h i c h signif icantly less than that required when using suture method. The electranyographical & histopathological studies a t 8 & 12 weeks postoperatively showed that the operative patency rate was over 95$, good t i s sue healing without any s ignif icant local adverse reactions were found & the early recovery was comparable with the results of suture method & further study of t h i s technique is warranted.

San-Chih L e e , Shigeru Amano, Kounosuke Jinnai, Kazusada Yoshitake, Fmitada Hazama, Thoru Tad, Takehisa Matsuda Dep. Oral & Maxillofacial Surgery ,%*a University of Medical Science Otsu c i t y , Shiga, Japan.

Artificial Organs, VoI. 13, No. 4 , 1989


185 NET ULTRAFILTRATION (UF) MAY NOT ELIMINATE BP.CKFILTRATION (BF) DURING H I G H FLUX HEMODIALYSIS (HFHD)

W e have r e c e n t l y d e m o n s t r a t e d t h a t EF c a n be d i r e c t l y measu red i n v i t r o d u r i n g HFHD a t z e r o n e t UF. BF r a t e s were d e t e r m i n e d a t l o w d i a l y s a t e f l o w r a t e (Qd) by measu r ing changes i n t h e l o c a l c o n c e n t r a t i o n of a macromolecu la r m a r k e r i n t h e d i a l y s i s s o l u t i o n t h r o u g h sampl ing p o r t s added t o t h e d i a l y z e r h o u s i n g . F u r t h e r s t u d i e s h a v e shown that BF ra tes a r e i n d e p e n d e n t of t h e r a d i a l p o s i t i o n o f t h e sampl ing ports (r.=3) and t h a t BF r a t e s a t Qd o f 100 ml/min w d e r e s t i m a t e those a t Qd of 450 ml/min (p<.Ol, n = 4 ) . The i n f l u e n c e o f n e t UF on BF w a s t h e n d e t e r m i n e d f o r 3 d i a l y z e r s w i t h d i f f e r e n t w a t e r p e r m e a b i l i t i e s (P) . I n v i t r o r e s u l t s (n=3) u s i n g whole b l o o d w i t h a b lood f low ra te of 200 ml/min and Qd o f 100 ml/min w e r e (mean + SD):

P n e t UF BF rate D i a l y z e r (ml/hr/mmHg) (ml/min) , (ml/min) FE 0 91 10 0 4.8 f 1.7

10 4.1 C 1.0 :'i l t r a l 31 i 5 0 1.5 f 0 . 4

10 n .d . GFS l 2 O P l u s 4 1 0 0.9 -f 0.6

1 0 n.d. n.d. i n d i c a t e s n o detectable BF. A t z e r o n e t UF, BF i n c r e a s e s w i t h i n c r e a s i n g P. N e t UF may l o w e r BF r a t e s b u t n o t i n d i rec t p r o p o r t i o n t o n e t UF. BF w a s e l i m i n a t e d a t a n e t UF o f 1 0 ml/min o n l y f o r d i a l y z e r s w i t h a l o w P. We c c n c l u d e t h a t d e s p i t e a s i g n i f i c a n t ra te o f n e t UF, EF c a n n e v e r t h e l e s s o c c u r d u r i n g HFHD. J c h n K. L e y p o l d t , B a r b e l Schmidt , Hans J. Gur land NeF8hrology Depar tmen t , Med ica l C l i n i c I , Klinikum G r o s s h a d e r n , U n i v e r s i t y of Munich, MLr.ich, F e d e r a l R e p u b l i c o f Germany

--

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187 NLLSCLE CXMFOSITION AND NUTRITIONAL nAl7J.S IN DIALYSIS PATIENTS

The nutr i t ional s t a tus in 25 dialysis patients was evaluated with conventional methods (such as anthropmetrics and serum proteins) and with determinations of muscle protein and high-energy phosphate s tores . Percutaneous muscle biopsies were taken a f t e r a n overnight fast i n 14 CAPD pat ients (8M/3F;59+13 ys;$ideal body weight (IBW) 104514%) and 1 1 HE pat ients (3M/8F; 38512 ys;IBW 92+32%) t o determine the r a t i o muscle alkali-soluble in t r ace l lu l a r protein (ASP)/DNA and the muscle contents of adenosine triphosphate (ATP), phosphocreatine (PCr) , f r e e (Cr) and t o t a l (TCr) creat ine (expressed as pg per g of dry muscle weight). The r e su l t s were compared with data from healthy controls ( C ) (n.81, for ASPDNA n:28): - ASP/DNA A T P PCr Cr TCr CAPO 286258a,b 21+3a,b 79211 47212 128215 HD 381279 2 623 94+7a m+io 143~iza

C 3495611 2423 7628 492 8 124+11

Mean 250. ap<G.Gl compared w i t h C , bp(O.01 compared w i t h HD

Muscle ASP/DNA (which is a sensi t ive index of protein depletion on the cel lular l eve l ) as well as muscle ATP were reduced i n CAPD but not in HD patients. In addition, serum a lbmin ( 3 3 4 and 39+3 g/L respectively) and midarm muscle c i rcmference (MAMC)-(26+3 and 30~4 an respectively) were lower i n CAPD than in HD patients. MAMC correlated with ASPDNA in the CAPD pat ients (r.0.57, p<O.E) whereas s e r m a l b m i n correlated with ASP/DNA i n the HD pat ients (r-0.69, p<0.05). These data indicate that 1) muscle protein deple- tijm and reduced muscle energy s to re s a re commonly found i n CAPD pat ients , 2) MAMC is a predictor of muscle protein de f~c iency i n CAPD pat ients , whereas 3) in HD pat ients s e w n albmin seems to be the s ingle best predictor of muscle protein s to re s as evaluated by ASP/DNA.

_- Liidholm B,Ahlberg M, b r a n y P, Heimbiirger 0, Pettersson E, Hultman E, @ergstr%m J. Dept of Renal Medicine and Clin Chem 11, Karolinska Ins t , Hu,lrlinge Univ Hosp, Stockholm, Sweden.

1% HEMOSTASIS OF SOLID VISCUS TRAUMA BY A NOVEL ELASTOMERlC SURGlCAL ADHESlvE

There are still many problems in the management of internal bleeding during surgery, especially, solid organs such as the liver, pancreas, spleen etc.Although many new materials and instruments have been developed for repair and hemostasis, they are not,as yet,totally satisfactory. Recently we have developed a novel elastomeric surgical adhesive, based on a hydrophilic urethane prepolymer.We used this material(PUP-134) in the management of internal bleeding in the dog & rat. Animals were anesthetized, surgically explored, and a solid organ crushed 01- cut. The sirface of the traumatized area was canpressed with a piece of teflon 01' silicon,which was painted with a very thin layer of PUP-134 (to prevent pseudomass fonnation),for about 2 minutes, and then removed. This material adhered very well to the tissue surface, preventing any bleeding.

and histopathologic studies(24hrs to one year after application) revealed a mild degree of inflannnatory reaction in the earlier stages. After 48hrs we found some organ adhesion over the treatment area, but this c d d be detached easi1y.After one year,tissue healing was almost canplete .These experiments demonstrated that this technique and material had the following advantages:l)rapid curing and adherence to the traumatized surface;Z)good elastmeric properties; 3 ) good healing;4) nontoxicity; 5)minjmal inflannnatory reaction;6) easy handling.

Kuo-Juei Lin, Thoru Tani, Kenji Numa, Hajime Abe, Toyokazu Yoshioka, Masashi Kodama 1st Department of Surgwy, Shiga University of Medical Science, Seta, Otsu, Japan

Gross

188 A R E T H E R E DIFFERL'NT YORPIIOLOGLCAL CHASGES CF PARIETAL PERITOSFL'M I N I)TXSETIC AND SOSDIAEiETJC I'REMIC ?ATIF.VTS PKIOR T I CXPD?

From J u n e 1983 t o !larch 1989 59 p a t i r n t s !ptsJ (28 men , 2 1 women) dged f rom 2 5 L O 78 v r s r s (36 .1516 .9 ) were t r ? a t c d w i t h C A P D . 2 3 of thei:i were d i a b e t i c s . 2 5 opened s u r g i c a l b i o p s i r j of p a r i e t a l per iconeum ( P P ) from t h e a n t e r i J r ohdo- m i n a l wa l l were r a d e d u r i n g i n s e r t i o n of CAI'D c a t h e t e r . 10 % n e u t r a l p u f f e r e d f o r m a l i n , Rrasi l -Bo: i in and McDowell were used f o r f i x a t i o n of P P . Spacecens were p r e p a r e d f o r l i g h t mic roscopy (he :na toxy l in e o s i n , T r i ch rome , Masson, PAS, van Gieson-h 'e igdrr SAB) and t r a n s m i s s i o n e l e c t r o n mic roscopy (OsO!. , Fpon 6 1 2 ) . I n d i a b e t i c s (DP) s u b m e s o t h e l i c c o l - l a g e n f i b e r s were m u l t i p l i e d compared w i t h nun- d i a b e t i c s (KP) and p e n e t r a t e d i n t o t h e sca rc i ' f a t t i s s u e . E l a s t i c f i b e r s were no t m u l L i p l i e d L O t h e same r x t e n t . The whole t h i c k n e s s of submesothc- l i um was 2 -3 t i n e s g r e a t e r a n d t h e d i s t a n c e o i f i r s t - l i n e s m a l l \ . e s s e l s from t h e meso the l ium was i n c r e a s e d 3-5 t i n e s . A b a s a l mrmbrnne of smal! v e s s e l s was c o n t i n u o u s i n DP t o o , b u t t1.ickc.r . The number of mast c e l l s was c o n p a r a b l e i n D? and Nl', mast c e l l s were r a r e and l o c a t e d i n t h e deep submeso the l ium n e a r v c s s e l s . O u r f i n d i n g s supporc a ctieory t h a t glucose i n p e r i t o n e a l d i a l y s i s s o l u t i o n c o o p e r a t e s i n i n d w c i n g p o s t r e a t n e n t changes o f PP, v e r i f i e d by b i o p s y i n p t s a f t e r o l ong- t e rm CAPD t r e a t m e n t program.

j . ~ i n d i i , A.F.Bren, D . F e r l u g n , J . D r i n o v r c , A.I lvala , A.Gufek, U n i v e r s i t y Y c d i c a l C e n t e r , Dp t . of Nephrology, ZaloSka 7 , 61000 L j u b l j a n a , Y u g o s l a v i a



189

19 1

PROPHYLACTIC INTRAVENTRICULAR PUMPING BY HEMOPUMF IN HIGH RISK CORONARY ANGIOPLASTY

The concept of left ventricular (LV) support during high risk angioplasty (PTCA) is widely accepted, despite the non availability of adequate non invasive system ! Hemopump, an original axial flow blood pump has been evaluated in this indication. The pump is inserted under local anesthesia, via the femoral artery, prior to any major maneuver on the coronary arterial system. Pumping is set to the maximal turbine speed permitting a 2 , 5 - 3,5 I./min. LV bypassed flow. The system has been evaluated on two patients, with an extremely severe coronary disease and a contra indication for aorto coronary bypass surgery. On both cases, an adequate support was obtained : increase in thermodilution cardiac index from 1,8 L/min/mz to 2 , 4 L/min/mz, drop from 18 mmHg to 14 m H g of the pulmonary wedged pressure. This improvement in haemodynamic indices was observed as LV rythmic disturbances, AV block and ventricular tachycardia, occurred tempo- rarily during the time of complete coronary occlusion. Mental alertness was maintained during the entire procedure. Angioplasty was successful in both cases. Hemolysis remained minimal PFH < 4 mg/dl during the 4 hours procedure.

Conclusion : Hemopump appears to be a safe and efficient technic f o r patients proposed for high risk.

D. Loisance, J.L. Dubois-Rand&, PH. Deleuze, M.L. Hillion, J. OkudC, J.P. Cachera, H. Geschdnd C.H.U. €icnri Hondor, Creteil, France

-~

Asialoglycoprotein Model Polymers f o r Hybrid

Recently, cultured hepatocytes can be applied to hybrid artificial liver as well as hepatic biosimulator. It should be important to design a good substratum for such hepatocytes culture systems. On hepatocytes surface membrane, the a.sialoglycoprotein (ASGP( receptor plays an important role on the clearance of ASGP from plasma. It is well-known that the ASGP receptor binds the nonreducing galactose residues of ASGP.

We synthesized some oligosaccharide-carrying polystyrene and attempted to apply them to culture of hepatocytes. can selectively attach on lactose-carrying pol - styrene (PVLA) surface. Calcium ion was indispensalbe for hepatocytes attachment to PVLA substratum, and hepatocytes attached on PVLA substratum were easily detached by treatment with EDTA. Moreover, the interaction between hepatocytes and PVLA depended upon microtubles, and had potentiality to attach at low temperature.

tain melibiose (PVMeA) o r cellobiose (PVCA) or maltose (PVMA) moieties, to examine the influence of different structure of oligosaccharide on cellular recognition. The polymers were investigated from a point of view of calcium ion dependency and cometitive inhibition effect of the polymers on hepatocytes attachment.

Artificial Liver.

It was found that hepatocytes

We synthesized other new polymers, which con-

Atsushi Maeda, Seishiro Tobe, Toshihiro Akaike, *Kazukiyo Kobayashi, "Hiroshi Sumitomo, Faculty of Technology, Tokyo University of Agriculture and Technology, 2-24-16, Nakamachi, Koganei, Tokyo 78L, *Faculty of Agriculture, Nagoya University, Chikusa, Nagoya 464

190

192

ANALYSIS OF ADSORBED SERUM PROTEINS (SP) ON THE ARTIFICIAL HEART (AH) BLOOD PUMP AND ITS INFLUENCE ON THROMBUS FORMATION (TF)

Though it has been suggested that TF on the smooth surface of biomedical polymers is influenced by the SP adsorbed, previous studies have not yet elucidated the SP effects.

The objectives of this study were to clarify what kinds of SP are adsorbed on the surface of AH pumps after long term pumping and how those SP would influence on platelet adsorption and TF in that region.

Sacs of the blood pump used in AH animal experiments and in clinical cases of ventricular assist device (VAD) were investigated. These sacs were made of polyvinyl chloride coated inside with anti-thrombogenic materials. The adsorbed SP (albumin, Ig-G, fibrinogen and compliments) were detected using a immuno-peroxidase stain. The adsorption of SP on the surface of the sac and its influence on TF was investigated by macroscopic observation of SP mapping on the surface of the sac and microscopic analysis of SP distribution in cross section.

Both albumin and Ig-G were adsorbed on the inner surface of the sac and the adsorbed albumin formed a uniform layer with a smooth surface; however the Ig-G layer was uneven, which may relate to TF in the region.

Quantitative evaluation of adsorbed SP on sacs used in clinical cases of VAD is now under study using radio-isotope conjugated antibody method and auto-radiography.

- K. Mabuchi, I. Sugawara", K. Imachi and K. Atsumi Institute of Kedical Electronics, Faculty of Medicine, University of Tokyo, JAPAN "Institute of Medical Science, University of Tokyo

ARTIFICIAL ORGANS AS A TOOL FOR F"SI0LoGIcAL INVRSTIGATIONS

The rapid growth of artificial organs (AO) was characterized by the development and clinical application of various devices and therapeutic procedures. While A 0 have had a major impact on present day health care, the utility of A0 as an investigative physiological tool is generally overlooked. In lipid apheresis, for example, the transport and metabolism of cholesterol can be quantified. Further, lipid apheresis can rapidly reduce the plasma levels of cholesterol to slow the progression of atherosclerosis and provide a means to study this disease process. Biliary solute removal by extracorporeal plasma sorption in jaundice is applied to investigate the modulation of immune functions. Such evaluations of the physiological consequences of biochemical or immune system abnormalities provide the rationale for further A0 development. In addition, the ability of A0 technologies to rapidly correct some physiological deficiencies and to regulate solute and cell concentrations provides a powerful investigative tool. In the maturing A0 field more efforts to use the technology as an investigative tool should be given. Such studies with A0 will contribute to our understanding of the diseased physiological system.

Paul S. Malchesky, Andrzej Werynski, Yukihiko Nose, The Cleveland Clinic Foundation, Cleveland, Ohio, USA



193 IMPROVED BIOCOMPATIBILITY BY PLASMA HODIFICATION OF SURFACE FOR CELLULOSIC DIALYSIS MEMBRANE.

Plasm, an ionized gazeous s t a t e of nnt ter , can be used f o r t h e chemical m d i f i c a t i o n of surfaces f o r biomater ia l a p p l i c a t i o n s . S u b s t i t u t i o n o f OH-groups f rom anhydroglucose u n i t of c e l l u l o s e i n f l u e n c e membranes propert ies such as protein adsorption and human conplement a c t i v a t i o n .

Carbon T e t r a f l u o r i d e (CF4) -Plasma i s produced by radiofrequency (13.56 MHz) discharges i n a reaction vessel where t h e pressure was 0.2 mntrg. The power input was 500 W and Cuprophan membrane samples were subni t ted t o ionized CF4 a c t i o n du r ing 15 minutes.

C a l i b r a t e d samples (5 cm2) of d i f f e r e n t d i a l y s i s membranes, Cuprophan (CU) , CF4-Plasm modified Cuprophan (F-CU) , Polyac ry lon i t r i l e (AN-69) and Polycarbonate (PC) a r e incubated i n 0 . 5 ml human normal serum (HNS) a t 37'C during 30 min f o r CSa-desArg generation rate evaluat ion. Incubat ion of NHS without membrane sample i n t h e same experiment conditions served a s control. Serum C3a-desArg concentrat ion w a s measured by r a d a i m o a s s a y (Amersham RPA 518) .

Non-treated CU membrane e x h i b i t e d h igh C3a-desArg generation r a t e (5232 f 412 ng, n - 9) compared t o t h a t of CF4-Plasm m d i f i e d F-CU membrane (2464 f 263 ng, n - 5 ) which i s i n t h e same range of t he basal generation r a t e of c o n t r o l experiments without membrane sample (2110 f 1 2 1 ng, n - 6 ) . PC membrane e x h i b i t e d l o w C3a-desArg gene ra t ion r a t e (2683 f 341 ng, n - 4 ) whereas AN-69 showed l i k e l y p r o t e i n a d s o r p t i o n s i n c e i t s appa ren t generat ion r a t e was lower (844 f 33 ng, n - 4 ) than t h a t of c o n t r o l experiments.

I t i s concluded t h a t CF4-Plasma mod i f i ca t ion of c e l l u l o s i c membrane s u r f a c e i s a b l e t o prevent human complement ac t iva t ion . P lasm technology, which i s clean and s imple, may be more promising than complex and contaminant o t h e r chemical processea.

U, G . Legeay, G. Jehenne, D. T ibe rgh ien , D . Delafaye. Hospi ta l Necker, P a r i s ; I .R .A.P . , Le Mans and Hospi ta l Vendbme, Vendbme: France.

195 MODULATION OF CLASS I AND CLASS I1 M H C EXPRESSION ON HUMAN ENDOTHELIAL CELL BY SHEAR STRESS

Expression of MHC class I1 antigens on human endothelial cells (HEC) might negatively influence the patency rate of small caliber

While MHC class I and class I1 expression has been documented on endotheliaf cells and their inducibility by IFN in viuo has been reported, very little is known of the physiological factors affecting this expression in vivo.We have investigated the effect of shear stress on the MHC expression of Human endothelial cells from the microvasculature(HMEC) HMEC were obtained from omenlal tissue during surgery. purified over Percoll gradient and plated on Primaria plastic dishes until1 confluence was obtained .All cells were positively stained using an anti factor VIII antibody. The cells were seeded on a Poly-L-Lysine precoated Aclar film for an over night and exposed 10 shear stress for 30 hours to a wall shear s u e s in the chamber with three pressure regimens:36 dynedcm2 (physiologic rate )20 dynes/cm2 and 80 dynesIcm2 Indirect immunofluorescent staining showed a homogenous increase of class I expression (W6-32) and appearance of class II(CA.206) expression in clusters of cells with very faint expression in other cells.Two types of cells were particularly brightly stained: rounded cells and elongated cells.S&nning electromicroscopy confirmed the "activated morphology of this population.Moreover precoating with fibronectin instead of poly-L-Lysine enhanced class11 labeling.Control in static system using gamma IFN(500u/ml) in thz medium presented the same staining. and the same cell shape change.Reversibility of class11 expression was observed when shear stress was discontinued. This provides a model to study the involvment of MHC expression in endothelial cell activation under physical constraint? ,in the atherosclerosis process,and in vascular surgery..

graft.

- Martin-Mondiere C*".Caprani A', Desgranges P* ,Charron D". * Centre de Recherches Chirurgicales, CHU CRETEIL FRANCE " !;ervice dHCmatologie CHU Pitit-SalpBuikre, PARIS FRANCE "INSERM 256,Hop.Broussais. PARIS, FRANCE

194 HEMOFILTRATION(HF) EFFICIENCY IMPROVEMENT BY ADDING fIEMOPERFUSION (HP)

We i n s e r t e d i n HF c i r c u i t (hcmofi l ter Hemoflow F80 s u b s t i t u t i o n f l u i d 30 1, p o e t d i l u t i o n j a c a r t r i d g e containing 70 g of collodion-coated a c t i v a t e d charcoal (Sorbex 70) i n order t o l n c r e a s e HF ef f ic iency . With t h i s method we t r e a t e d 5 chronic uremic p a t i e n t s f o r 12months. Previously they had been t r e a t e d with HF only f o r 6 months. The clearances (ml/min) determined a f t e r 60 min from the beginning of the session, with blood flow 300ml/min, were the following: HF HF+HP Incr . Urea 114215 128210 + 12% Creat inine 114+15 179+ 6 + 57% Uric ac id 115z 7 219212 + 85% Beta-2- Microglobulin(B2M 742 6 148210 +low Parathonnone (PTBi 77+ 5 141+ 8 + 83%

months of HF+HP treatment ,decreased as follows: urea -7.5%, c r e a t i n i n e -2M, u r i c ac id -1696, B2M -2296, PTH -3796. The r e s u l t s show HP addi t ion t o H F increaees remarkably c r e a t i n i n e , u r i c a c i d , B2M, PTH removal, while urea removal increase is negl ig ib le . Therefore we th ink the method HF+HP can show an i n t e r e s t i n g development i n the treatment of p a t i e n t s with high serum levels of uremic t o x i n s which are not e f f i c i e n t l y removed by conventional blood p u r i f i c a t i o n methods. R .Marangoni ,F .Civardi ,R .Savino ,A .Manfredi, C.Avanzi,F.Hasi,R.Cimino,R.Colombo Nephrology and Dialysis Unit, Ospedale d i Bol la te , Bollate-MI, I t a l y

P r e d i a l y t i c values, 8etermin;d a f t e r 12

196 HUMAN ENDOTHELIAL CELLS TREATED AS EXTRACELLULAR MATRIX DOES NOT INDUCE CLASS I1 MHC EXPRESSION ON HOMOLOGOUS ENDOTHELIAL CELL SEEDED.

Activation of human adult endothelial cells (HAEC) is known to be a procoagulant event. Presence of Class11 antigen of the major histocompatibility complex (MHC) is a good marker of activation for HAEC. Endothelial cells from microvasculature express collagen IV and laminin on their membranes. Both of them have adhesive properties for HAEC and no thrombogenic effecth this study, HAEC were treated as exmcelliular manix and used for cell seeding as well. Presence of ClassII antigen has been evaluated on monolayer endothelial cells grown on these exaacellular matrix. HAEC were purified from fresh omental tissu, minced, washed, digested in a mixed solution of collagenase-dispase, passed under meshs. Cells were selected on a Percoll gradient, plated on Primaria plastic dish for 3/4 days, until confluence. They are tested with factor Vl l I and W6-32 antibodies, using indirect immunofluorescence. Extracellular matrix (ECM), prepared according to our own method consisting in enrichment of bFGF. Confluent layer was treated by hypotonic choc.which preserve biochemical structure of ECM and its ability to present bFGF. ECM were seeded with autologous and homologous HAEC Expression of Class I and Class I1 of MHC was studied using monoclonal antibodies: W6-32 for Class 1, CA.206 for Class 11, with an indirect immunofluorescence technique. Results showed an homogenous layer with a cobblestone morphology. No change affected Class I and Factor VIII expression.Class I1 was present only on round likely dividing cells. No difference was observed between auto and homologous experiments Homologous HAEC treated as ECM appear to be suitable to induce human endothelial cell lining in arterial implants.

Martin-Mondiere C"*, Desgranges Po-,Tardieu M-, Bmitault D-, Charron D* ' Cenue. de Recherches Chirurgicales, CHU CRETEIL FRANCE * Service dHCmatologie CHU Pitit-Salp&iere, PARIS FRANCE -Lab. de Biotechnologie ,Universitt Paris XII, FRANCE



197 DEVELOPMENT OF PORTABLE SPEECH INPUT DEVICE FOR CONTROL OF MOBILITY FUNCTIONS

OF PARAPLEGICS.

Current methods for controlling Functional Electrical Stimulation (FES) systems that restore standing and walking in persons with paraplegia rely on hand activated switches mounted on crutches or walkers. Voice command of FES systems may be a more flexible method of control. Such systems will need to be portable and reliable, but may require recognition of only 16 to 32 commands. We have developed a voice recognition system based on a multilayered network technology. We have tested a bread-board version of the system using a desktop computer and found that its recognition accuracy for 16 command words was 97%. The system is now being implemented in a portable form which fits into a box of 19x1 1 x5 cm. It consists of a microphone and detector which produces a pulse for each zero crossing of the filtered microphone voltage. A micro- processor tmnsforms these pulses into an array of 32 zerocrossing frequencies, and according to the multilayered network, which is constructed during the training mode, sends 1 of 16 commands to the stimulator. The hnction of this neuroprosthetic input device will be demonstrated.

Susumu Maruno, Andrew Schoenberg Physical Medicine and Rehabilitation Div. , Medical Center

University of Utah, Salt Lake City, Utah, USA

199 A HAND-MADE VALVED CONDUIT WITH HIGH-POROSITY KNITTED GRAFT AND GLUTARALDEHYDE-TREATED AUTOLO- GOUS PERICARDIAL TRILEAFLET VALVE

Considering high incidence of late obstruction of the xeno-graft valved conduit utilizj-ng low- porosity Dacron graft and also from the limited availability of fesh or cryopreserved allograft, we introduced a new composite valved conduit of low porosity knitted graft (Milliknit; Golaski Lab.) with hand-made pericardial trileaflet valve (PV). At operation, a rectangular strip of autologous pericardium was tanned by glutaraldehyde and sewn inside of the preclotted graft as a t r i - leaflet valve. Its clinical efficacy as right ventricle to pulmonary artery (PA) extracardiac conduit was evaluated in consecutive 10 patients with various complex cardiac lesions (age: 4-23, average 7.8 yrs). The graft size was 16 to 22 mm. There were 2 operative deaths, 1 with single ventricle and transposition, and another with palliative conduit repair, but the causes were not related to the conduit. Eight patients mainly of tetralogy of Fallot with PA atresia tolerated the surgery well and survived. The graft was very pliable and its conformability was excellent as of the allograft. At the follow-up of 3 to 23 months (average:9 months), Doppler study showed trivial or only mild valve regurgitation of the condiut PV. Platelet scintigram showed no apparent deposition of the platelet at the region of the conduit (n=3). Although long- term follow-up is required, the result indicates that this new valved conduit may be useful as an alternative to the xeno- or allograft conduit. Hikaru Matsuda, Katuhiko Miyamoto, Hiroaki Kawata, Yosihisa Tokuan, Yasunaru Kawashima 1st Dept. Surgery, Osaka Univ., Fukushima, Osaka, 553 Japan

198 ANALYSIS OF THE CLINICAL FACTORS FOR THE SURVIVAL AFTER LEFT HEART BYPASS USING VENTRICULAR ASSIST DEVICE FOLLOWING OPEN HEART SURGERY

Clinical factors affecting the survival were analyzed in 7 pts who received LVAD after open heart surgery last 2 yrs.

Group-]: Three infants with complex cardiac lesions(age:5 to 11 mon), required 6 3 , 64 hrs and 13 days support using BP-50(Bio-Pump). All pts were weaned, but 2 died within 1 week from infection and cerebral injury. One with left AV valve replacement died 8 weeks after prolonged support(l3 days) from renal failure and infection.

Group-;?: I n the other 4 pts(age 15-67 yrs), 2 with coronary artery bypass and 2 with aortic valve replacement, LVAD was performed using BP-80 (Bio-Pump) in 3(32-126 h r s ) and pulsatile assist device(Toyoioj in l(3 days). One patient died on LVAD ( 5 days) from multiorgan failure(M0F) with persisting high venous pressure. The other 3 pts were weanea(32, 86, 86 hrs) and survived. The interval between the initial attempt to wean from cardiopulmonary bypass and the start of LVAD was short in t::e survived pts(n=3, <4.5 hrs) than a non-survivor(8 hrs). Catecholamine doses during LVAD was also large (3 drugs) in a non-survivor and minimum in survivors(1-2 drugs).

These results indicated that: 1)the poor long- term result in infants was due to severity of the anomalies and the susceptibility to infection and other complications, and 2) in adult, long-term survival rete may increase by starting LVAD without delay and switch to biventricular assist if LVAD alone is insufficient to prevent MOF. Hikaru Matsuda, Ryousuke Matsuwaka, Mitsunori Kaneko, Takafumi Washi, Katsuhiko Miyamoto, Toru Kobayashi, Yasunaru Kawashima, First Dept. Surgery, Osaka Univ., Osaka, Japan

200 Novel Surface Modification Technology Based on Photoreactive Chemistry

This paper addresses to develop a novel sur - face modification technology based on photoreactive phenyl azido chemistry. The principle behind this is that phenyl azide is converted to highly reactive nitrene by UV-irradiation(250- 340nm) under ambient conditions, resulting in spontaneous formation of covalent bonding.

The surface modifications were carried out by two alternative methods. One is via irradiation of cast polymers or adsorbed by proteins, both of which are chemically pre-modified with phenyl azide groups. The other is via surface modification by bifunctional reagent having phenyl azide and activated ester groups and subsequent reactions of adsorbing proteins or cast polymers with surfaces. The examples of the first approach were demonstrated: polystyrene films were cast by hydrophilic dimethyl acrylamide copolymers or adsorbed by proteins pre-modified with phenyl azide groups. The films were then UV- irradiated. ESCA and contact angle measurements evidenced that cast polymers or adsorbed proteins were chemically fixed on surfaces upon irradiation. The hydrophilically modified surfaces drastically reduced both platelet and endothelial cell(EC) adhesion. Two-dimensional patterning of adhered ECs were demonstrated by patterned UV-irradiation.

Thus, the newly developed surface modification technology finds various applications including modification of fabricated devices.

Takehisa Matsuda, Kazuhiko Inoue, Eiichi Ozeki, and Tetsuzo Akutsu, National Cardiovascular Center, Suita, Osaka 565, Japan



201 Novel A r t i f i c i a l Matr ix: Solu t ion-Cas tab le C e l l Adhesion-Promoting Polymers

Recent s t u d i e s on c e l l b io logy have iden- t i f i e d t h e t r i p e p t i d e . RGD(Arg-Gly-Asp), as t h s minimal amino a c i d sequence common t o adhes ive s i t e s of adhes ive p r o t e i n s such as f i b r o n e c t i n and f i b r i n o g e n . This prompted u s t o develop s o l u t i o n - c a s t a b l e polymers having RGD-containing p e p t i d e , GRGDSP(G1y-Arg-Gly-Asp-Ser-Pro).

The s t a r t i n g v i n y l monomers used a r e N- methacryoxy succ in imide and N-vinyl benzoyloxy succ in imide . The a t tempt t o p r e p a r e macromers k- i th GRGDSP as a s i d e cha in v i a d i r e c t r e a c t i o n w i t h t h e s e monomers r e s u l t e d i n u n s a t i s f a c t o r y y i e l d . However, r e a c t i o n s of GRGDSP w i t h copolymers composed of t h e s e v i n y l monomers having ac- t i v a t e d e s t e r and o t h e r v i n y l monomers ( s t y r e n e and methyl methacry la te ) s u c c e s s u f u l l y incor - pora ted GRGDSP i n t o s i d e cha ins . This was con- f i rmed by s p e c t r o s c o p i c analyses(1R & NMR). ESCA measurements showed t h a t t h e outermost l a y e r s of c a s t f i l m s c o n t a i n GRGDSP r e s i d u e s . Upon immersion i n t o water , h y d r o p h i l i c GRGDSP f r a c t i o n w a s sur face-enr iched . Bovine en- d o t h e l i a l c e l l s ( E C s ) adhered w e l l on GRGDSP- c o n t a i n i n g polymer f i l m s i n t h e presence o r absence of serum. The de laminat ion of adhered E C s spontaneous ly occured by a d d i t i o n of RGDS.

Thus, s o l u t i o n - c a s t a b l e GRGDSP-polymers could s e r v e a s a r t i f i c i a l basement m a t r i c e s f o r c e l l c u l t u r e and hybr id a r t i f i c i a l o rgans , i n which c e l l adhes ion i s d r i v e n by molecular r e c o g n i t i o n of a r t i f i c i a l l i g a n d by c e l l adhes ion r e c e p t o r s .

Takehisa Matsuda, E i i c h i Ozeki and Tetsuzo Akutsu, Dept. Bioengineer ing , N a t i o n a l Car- d i o v a s c u l a r Center , S u i t a , Osaka 565, Japan

203 ELOOD ACCESS FOR PLASMAPHERESIS

The making o f b lood access is impor tan t p r o c e s s f o r t h e t r e a t m e n t of p lasmapheres i s . We s e l e c t s u i t a b l e method for t h e p a t i e n t among t h r e e t y p e s of blood a c c e s s depending upon t h e o r i g i n a l d i s - e a s e . For 16 p a t i e n t s w i t h hemorrhagic tendency due t o f u l m i n a n t h e p a t i c fa i lure , s u r g i c a l i n s e r - t i o n of double lumen c a t h e t e r t o r t . femoral v e i n v i a g r e a t e r saphenous ve in i s performed. On t h e o t h e r hand, t h e double lumen c a t h e t e r t o s u p e r i o r vena cava v i a r t . s u b c l a v i a n v e i n by b l i n d punc- t u r e w a s i n s e r t e d t o 6 p a t i e n t s wi th m u l t i p l e myeloma showing no ev idence o f hemorrhagic tendency.

I n t e r n a l a r t e r i o - v e n o u s shunt was a p p l i e d t o 8 p a t i e n t s wi th rheumatoid a r t h r i t i s and 3 p a t i e n t s with immune complex d i s e a s e who needed p e r i o d i c t rea tment of plasrnapheresis . However, t h e suc- c e s s f u l ra te o f shunt patency f o r t h e s e p a t i e n t s i s only 25%. When t h e r e c o n s t r u c t i o n of i n t e r n a l shunt seems t o be d i f f i c u l t , w e perform t h e arte- r i a l s u p e r f i c i a l i z a t i o n of b r a c h i a l or s u p e r f i c i a l femoral a r t e r y . The s e l e c t i o n of s u i t a b l e blood a c c e s s depending upon t h e o r i g i n a l d i s e a s e and t h e p a t i e n t s v e s s e l c o n d i t i o n is e s s e n t i a l l y important f o r t h e t r e a t m e n t o f plasrnapheresis . Jun-ichi Megurox, Kazutaka Kukita*, Motoki Yonekawai, Akio Kawamura', Nobuhiko Abe**, K?.zutoshi Setox*, Naoki Kobayashi*+, T a t s u r o I r i e **, Ken-ichi Kawarnura**, Toshio H i & a * * , Masaharu Kasai**, Te izo Ariyama***, Keiko Makita**** *Uept. of S u r g e r y , **Dept. o f I n t e r n a l Medicine, Sapporo Hokuyu H o s p i t a l , Ar t i f i c i a l Organ & Trans- p l a n t a t i o n H o s p i t a l , Sapporo, ***znd Dept . o f Surgery, Asahikawa Medical Col lege , Asahikawa, ****ls t Dept. of Surgery , Hokkaido Univ. , Sapporo, Japan

202 CAHDlAC FUNCTION ESTIMATION UNDER PUMP-ON CONDITION TO DECIDE WEANING TIME FROM LVAD

To dec ide weaning t i m e f rom t h e LVAD wi thout expos ing p a t i e n t s to d a n g e r , a c a r d i a c func t ion est imat ion method wi thout d i scont inuing pumping was proposed . Because t h e le f t v e n t r i c l e a n d the L V A n feject blood i n p a r a l l e l i n a t r i o - a o r t i c b y p a s s , i n t e r f e r e n c e is f o u n d i n severai hemo- dyrlainir. parameters . If t h e damage of t h e h e a r t is s e v e r e a n d t h e e n t i r e c i rculat ion i s maintained b y l h e assisL p u m p , t h e b o t h h e a r t s s c a r c e l y i n t e r f e r e with each o ther . However, a c c o r d i n g to t h e recox-erj of t h e d i s e a s e d h e a r t , t h e h e a r t ejects more blood a n d t h e d e g r e e of t h e in te r - f e r e n c e increases . T h e d e g r e e of t h e i n t e r f e r e n c e r e f l e c t s t h e f u n c t i o n of t h e n a t u r a l hear t .

Art L V A D w a s i m p l a n t e d b e t w e e n t h e left a t r i u m a n d t h e a o r t a of six mongrel d o g s a n d was driven in a s y n c h r o n o u s mode. Changing de lay ( T d ) e v e r y 10% of c a r d i a c per iod , hernodynamic f luc tua t ion w a s m e a s u r e d i n both t h e i n t a c t a n d corormry-l igated h e a r t s . In t h e i n t a c t condi t ion, t h e p u m p f l o w f l u c t u a t e d i n t h e r a n g e of 610ml/nr in/ lOkg (Td=O%; c o - p u l s a t i o n ) a n d 310 (Td=50%; c o u n t e r p u l s a t i o n ) . H o w e v e r , i n t h e damaged h e a r t , the r a n g e d e c r e a s e d to 54O(Td=O%)- 470(Td=50%). T h e r e d u c t i o n of t h e f luc tua t ion was a l s o o b s e r v e d i n cardiac o u t p u t , l e f t a t r i a l p r e s s u r e , arid arterial p r e s s u r e . Same r e s u l t s w e r e o b t a i n e d from beat-by-beat a n a l y s i s of t h e hemodynaniics u n d e r a n a s y n c h r o n o u s pumping.

From t h e a b o v e r e s u l t s , i t c a n b e concluded t h a t t h e w e a n i n g t i m e is d e c i d e d f r o m t h e hernodynamic f luc tua t ion w i t h o u t expos ing patients t o d a n g e r .

Y.Mi mum2, K.0taki3. k:In:t?zl.ELect. , Znd.Qept.S~rg.~, Hokkaido Univ.; Hokkaido Tokai Univ.', Sapporo , J a p a n

ti' .M ts

0.x laboratory has been working on an a r t i f ic ia l ventricle since 1983. As a result, we have developped a mdified technique for a t r ia l cannulation that avoids mny of the difficult problem posed by cannulation at this location. Atrial shunting i s carried out without extracorporal circulation or a t r ia l clanping, using a Lkcron tube. ?he purpose is to describe the technique as it was used in m r e than 1CO experimnts on sheeps and calves. We stress a few points of irrportance for clinical applications : with this technique, the risks €or herorrage, gaz &li, disconnecting fran the a t r im, secondary displacmnt inside the heart are significantly lower. In case of tenporary circulatoly assistance, the explantation is facilitated.

We conclude that our mdified technique using a Dacron connector i s better than convent io~al techniques in tern of reproducibility, sirrplicity , and long-term reliability.

It can be suitable for short tenn or penranent assistance using any type of a r t i f ic ia l ventricle.

T. bsana, J.R. kn t ihs , P. Havlik, P. hracciole, J.J. Pa&e, R. Gulino. - Labratoire de Recherches aimrgicales - Marseille.



205 PERIOPERATNE D I E f S I S OF PATEWTS WITH GASTROINTESTLNAL DISORDERS INDICATED TO SURGICAL TREATICW.I!

A long-term survey of opera t ive f i l e s e s t a b l i s h e d t h a t major number of p a t i e n t s surgicalLy t r e e t e d f o r co lo- rec ta l cancer (CRC) died a f t e r opera t ion due t o heavy r e n a l d i sorders . Another oup o f p a t i - e n t s on haemodialysis (HDYsuffered seve- r e b leedings due t o exacerbated gas t ro in- t e s t i n a l d i s e a s e s and were i n d i c a t e d t o opera t ion too. Based on t h i s f a c t , t h e a u t h o r s o f p resent s tudy analysed d a t a o f co l labora t ion betaeen nephrologist-haemo- G i a l g s i s t , s u g e o n end i lmunologis t exa- a i n a t i n g p a t i e n t s on HD i n d i c a t e d t o ope- r a t i o n end v ice versa . A t o t a l o f 1 4 pa- t i e n t s vere s t u d i e d i n 2 groups: I - ma- l i g n a n t : 6 cases viith CRC ( 4 n i t h chronic r e n a l f a i l u r e p r i o r t o o2era t ion and 2 mith acute r e n a l f a i l u r e n f t e r ) ; s L . r g i c a l t reatment : abdomino-perineal e - r t i rpa t ion ( K i l e s ) , Iiartnnn o?era t ion , sphincteropre- se rv ing operat ion. I1 - benignant: 8 pa- t i e n t s on HD %.-{ith g a s t r o i n t e s t i n a l complica t ions : 6 exacerbated u l c i , 1 acute ulcus and 1 ulcus + haemorrhagic g a s t r i t i s . B-11-Ron and vagotonia t r u n c u l a r i s e e r e t h e opera t ive i n t e r v e n t i o n s f o r t h i s group, By qi,r,plying both, IiD cnd s u r g i c z l t reatment i n combination, a l l p a t i e n t s viere a l i v e 6 months af te i - ogera t ion except 1 (acute heenorrhage). Concl.>sion: a c t i v e c o l l a b o r a t i o n - e f f e c t i v e r e su l t s .

Kr.Metodiev, M.Bojkov, D.Nenov Higher In s t . LIedicine, 9002 Varna, Bulgar ia

BIOSPECIFIC SORBENTS F O R M E D I C A L U S E BAS- ED O N SYNTHETIC ACTIVE CARBONS

S y n t h e t i c a c t i v e c a r b o n s (SAC) o f v a r - i o u s p o r o s i t y a n d s t r u c t u r e a r e w i d e l y u s e d for s o r p t i v e d e t o x i c a t i o n o f body flu- i d s a n d wounds. T h e i r t h e r a p e u t i c a c t i o n i s b a s e d on t h e a b i l i t y t o remove n o n s e l e - c t i v e l y v a r i o u s s u b s t a n c e s m a i n l y w i t h low m o l e c u l a r w e i g h t . I n o r d e r t o p r o v i - de them s e l e c t i v e p r o p e r t i e s we d e v e l o p e d me thods o f p h y s i c a l and c h e m i c a l i m m o b i l i - s a t i o n of p r o t e i n s i n c l . a n t i b o d i e s , e n z - ymes , a n t i g e n s a n d o t h e r c l a s s e s o f chem- i c a l compounds ( D N A , ATP, a m i n o a c i d s ) . The c h o i c e o f t h e i m m o b i l i s a t i o n t e c h n i q - u e d e p e n d s on t h e d e s i r e d a i m o f t h e s p e - c i f i c s o r b e n t : f o r b a n d a g e s on wounds phy- s i c a l a d s o r p t i o n i s s u f f i c i e n t b e c a u s e t h e l i g a n d l e a k a g e from t h e s u r f a c e u s u a l - l y i s n o t d a g e r o u s . T h i s a p p r o a c h i s impo- s s i b l e i f t h e s o r b e n t h a s t o c o n t a c t w i t h b l o o d or p l a s m a . Only c o v a l e n t l i n k a g e en- s u r e s i r r e v e r s i b l e a t t a c h m e n t of t h e l i g - and t o t h e s u r f a c e as it w a s shown by ra- d i o i s o t o p i c a n d f l u o r e s c e n t s t u d i e s i n t h e s y s t e m s w i t h i m m o b i l i z e d m y e l i n e b a s - i c e n c e p h a l y t o g e n i c p r o t e i n , 18,5 kD a n d a n t i - I g C r a b b i t . SAC w i t h i m m o b i l i z e d ATP p r o v e d t o remove s e l e c t i v e l y h e a t - s h o c k p r o t e i n s f rom mode l p l a s m a ; SAC w i t h c o v a - l e n t l y c o u p l e d I g G - r a b b i t a p p e a r e d t o b e s e l e c t i v e s o r b e n t s t o w a r d s a n t i - I g G r a b - b i t i n t h e p r e s e n c e o f t h e o t h e r p r o t e i n s . B i o s p e c i f i c SAC a r e s t a b l e f o r 3-6 mon ths . M i k h a l o v s k y S . , Noscov A . , A l e k s e y e v a T . , M e t a l ' n i k o v a N., G u r i n a N . I n s t . G e n e r a l I n o r g a n i c C h e m i s t r y , I n s t . Onco logy P r o b l e m s , K i e v , U S S R

206 DUF'LEX WPPLER ULTRASSKGRAFWIC EVALUATION OF RENAL ALLCGFLAFE

h p l e x Doppler sonography has been used r ecen t ly i n the d iagnos is of acute r e j ec t ion . Moreover. t h i s method is usefu l t o de t ec t many o the r com- p l i c a t i o n s of rena l a l l o g r a f t s . We have evaluated 24 p a t i e n t s a f t e r r ena l transplantation ( 1 2 with normal rena l func t ion , including 2 with lymphoce- l e , end 12 with func t iona l derangements: 3 with acute r e j e c t i o n , 2 with chronic r e j ec t ion , 2 with obs t ruc t ive nephropathy. 3 with rena l a r t e r y s t e n o s i s , 2 with cyclosporine-induced tubular da- m a g e ) . me ultrasonographic examinations w e r e performed with a duplex doppler scanner (Toshiba SAL 100). W e used 3 . 7 5 and 5.00 MHz l i nea r probes f o r the morphological evaluation ( r ena l a l l o g r a f t pos i t i on ; longi tudina l max diameter; parenchymal thickness: rena l cross-sectional area: co l l ec t ing system; pararenal space). W e employed a 2 . 2 5 M H z duplex phased a r r a y sec to r probe for t he blood flow eva lua t ion (main renal a r t e r y : segmental, i n t e r loba r and arcua te a r t e r i e s ; rena l v e i n ) . The r e s u l t s w e obtained demonstrate the u t i l i t y of duplex doppler sonography i n the follow-up of renal a l l o g r a f t p a t i e n t s .

V . Migaleddu*.M.Cossu.G. Simonetti*.C.B. S o r b Divisione d i Nefrologia e D i a l i s i . USL 1; and * I s t i t u t o d i Scienze Radiologiche. Universita d i Sassa r i . 07100 S a s s a r i , I t a l y

208 EFFECT OF GLUTARELDEHYDE CONCENTRATION ON COLLAGEN

C R 0 S S U " G AND ABSORPTION.

Collagenous tissues for implantation are generally treated with glutaraldthyde in saturating concentxations (0.5% w/v or greater). These tissues have been shown to be highly resistant to degradation and to elicit minimal immunogenic response. Although highly successful for porcine hem valves, this treatment has not been successful for the trearment of orthopaedic xenograft tissues (e.g. tendon and ligament), the treated material being too stiff and failing to form adequate junctions with tendon or bone.

(GA) concentration on the mechanical and biological Propcmes of tendon kangaroo tail tendon (approx. 1-2 cross-section) has been mated with GA from 0.01% w/v to 0.5% w/v in phosphatc/citntte bnffer pH7.4, then sterilised by 25OkGreys of gamma irradiation. The ternpratm of onset of t h d d e n a d o n . Td, of the treated tendon has been determined and samples have been implanted intramuscularly in rabbits,

previous studies have shown only marginal difTerences in mechanical properties between unmated and 2% w/v GA-trcatcd tendons. The thermal denaturation studies showed little iacrcaSt in Td at 0.01% w/v GA. a rapid rise in Td with GA trcatmnt from 0.02596 to 0.075% w/v GA and appmnt d o n of crosslinking above 0.1% w/v GA. Tmument by GA within the concentration mge examined should aUow controllad resorption to occur.

To examine the effect of a range of glutaraldehyde

BX-Miltharpc, KSCbindhc~ and s.c.Roe Centre for Bkndical Engineering Univmity of New South Wales, AUSTRALIA

Artficial Organs, Vol. 13, No. 4, 1989


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IN V I T R O AND I N V I V O EVALUATION OF A NEW HOVING- ACTUATOR TYPE ELECTROMECHANICAL TOTAL ARTIFICIAL HEART. A new type o f e lectromechanical t o t a l a r t i f i c i a l heart(TAH) based on t h e c i r c u l a r r o l l ing-cyl inder mechanism was developed t o overcome t h e c r i t i c a l problems i n motor-dr iven a r t i f i c i a l hear t such as la rge s ize and d i f f i c u l t i e s i n f i t t i n g the hear t t o a t r i a l remnant and a r t e r i a l vessels. The new blood pump cons is ts o f th ree major pa r t s : r i g h t and l e f t v e n t r i c l e s and pump actuator i nc lud ing a small s ize , h igh to rque brushless dc motor as an energy converter. The t o t a l weight and volume o f the pump are 7909 and 660m1, respec t ive ly . The a r t i f i c i a l v e n t r i c l e i s a polyurethane (Pel lathane , BOW Chemical) b lood sac and i n the pump ac tua tor , t h e motor r o l l s back and f o r t h on a c i , - cu la r t rack , which causes the a l te rna te blood e jec t i on . The performance and r e l i a b i l i t y o f the pump were evaluated i n mock c i r c u l a t i o n and animal implant experiments. The r e s u l t s o f mock c i r c u l a t i o n tests show t h e s u f f i c i e n t cardiac o u t p u t o f S(L/min) a t t h e a o r t i c pressure of :SO(mmHg) and the hear t r a t e o f 12O(BPM). I n i n v i vo experiment, t h e pump was implanted i n a c a l f ( m o u t 100Kg) f o r t o t a l hear t replacement, and i t had been operated f o r 100 hours w i th the animal 's exce l l en t phys ica l cond i t i on . The whole system i i c l u d i r i g pump, c o n t r o l l e r , and con t ro l a lgor i thm has performed we l l t o improve the prospect o f c l i n i c a l app l i ca t i on o f our TAH system.

BWun4 G. MA, Hee C. K i m , Sang H. Lee, I n Y . kim, .Jong W . K i m , J i n W. Choi, J i n T . K i m , Dae Y . Jung 3epartment o f Biomedical Engi neer-1 ng, College o f Medicine, Seoul Nat ional Un ivers i ty .

SCANNING mCI'R0N MICROsoOPIC(SEC4) STUDIES ON aRAmcs/BLooD l3rmWAE

F i n e ceramic h e a r t v a l v e , c o n s i s t i n g of a s i n g l e c r y s t a l a l u m i n a d i s c a n d t i t a n i u m n i t r i d e ( T i N ) hous ing , h a s been s u c c e s s f u l l y implanted i n sheep (J. Biomater. Appl., i n p re s s ) . In t e rac t ion &tween ceramic raterials and p l a t e l e t w a s s t u d i e d i n d o g s t o i n v e s t i g a t e b l o o d compat ib i l i ty of ceramics.

A test r ing w a s implanted i n t h e i n f e r i o r vena cava i n 10 dogs f o r 2 hours. The r i n g was 7 mm i n inner diameter, 8 mm i n o u t e r diameter, and 9 m i n l e n g t h . T e s t materials w e r e s i n g l e c r y s t a l alumina, TiN, po lyc rys t a l l i ne alumina, segmented polyurethane (Toyoh , TM-3), s i l i c o n e (P ie rce , S u r f a S i l ) , and g lass . Af t e r t he experiment, the test material w a s f i xed i n 2.5 % glutaraldehyde, dehydrated by ethanol, and dried by c r i t i c a l - p o i n t method. The t es t material was examined by SEM every 100 p from t h e edge of the r ' ng . N d r of p l a t e l e t s i n t h e area of 50 X 50 p i was counted.

A d h e 5 e q p l a t e l e t s w e r e 161 2 1 7 (mean S.E.)/10 p ( ~ 4 1 ) on s i n g l e crystal alumina, 285 - + 3 5 ( n = 1 9 ) o n T i N , 360 k 3 7 ( n = 2 1 ) o n p o l y u r e t h a n e , 4 3 0 2 3 ( n = 2 5 ) o n p l y c r y s t a l l i n e alumina, 439 31 (n=5) on g l a s s , and 534 '+ 64 (n=15) on s i l i cone . P l a t e l e t s w e r e s i g n i f i c a n t l y ( ~ ~ 0 . 0 1 ) few on s i n g l e c r y s t a l a lumina compared w i t h o t h e r materials. Also : : . g n i f i c a n t l y f e w p l a t e l e t s a d h e r e d o n TiN compared w i t h s i l i c o n e (p<O.Ol), g l a s s (pc0.05), a d po lyc rys t a l l i ne alumina ( ~ ~ 0 . 0 5 ) .

It can be concluded that s ing le crystal alumina and TiN have weak i n t e r a c t i o n w i t h p l a t e l e t , and have good blocd compat ib i l i ty . Y.Mitamura*, K . G t a k i * * , T.Yuta**, and T.Mikami** * F a c u l t y of Engnq. , H o k k a i d o T o k a i U n i v . , Sapporo, Japan, ** Hokkaido Univ., Sapporo, Japan

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HEMODIALYSIS AND ACTIVATION OF SERUM LYSOSOMAL EN2YMES:FROM A VIEW POINT OF RELATIONSHIP TO AMYLOIDOSIS

Possible relationship of se rum lysosomal enzymes wi th development of amyloidosis was studied in pa t i en t s w i t h or without hemodialysis. M e t h o d s : Four types of lysosomal enzyme ( a c i d phospha t a se , g lucuroni dase , g lucos i dase , d ipep t idy l aminopept idase) ac t iv i t i e s i n sera of 2 4 p a t i e n t s w i t h HD and normal subjec ts were measured by fluorescent techniques . Resu l t s :The values of se rum lysosomal enzyme a c t i v i t i e s i n HD p a t i e n t s were s i g n i f i c a n t l y h igher than those of continuous ambu la to ry pe r i tonea l d i a l y s i s (CAPD) p a t i e n t s , non-HD chronic r ena l f a i l u r e pa t i en t s or normal c o n t r o l s . Rapid increase in these enzyme a c t i v i t i e s w i t h t r a n s i e n t leukocytopenia was seen in a lmos t a l l the p a t i e n t s d u r i n g HD. Moreover, a n ascending r a t io of enzyme ac t iva t ion caused by HD was s ign i f i can t ly h ighe r i n the g r o u p of p a t i e n t s with amyloidosis. The re was a co r re l a t ion of ac t iva t ion of lysosomal enzymes such a s p ro teases , w i t h serum Bz-microglobulin levels which migh t be i n t e r r e l a t e d t o the deve 1 opmen t of d i a lys i s amy 1 oidosis . Conclus ion: HD may cause a n increase in lysosomal enzyme a c t i v i t i e s in the serum, poss ib ly r e spons ib l e fo r the pa thogenes i s of amy 1 o i do s i s . Minakuchi,J., Kawachima,S., Saito,A., Sa to ,A . , Natori ,Y., Kawashima. Hosp., Tokushima, Shinseikai Daiichi Hosp., Nagoya, Tokushima Univ., Tokushima Japan

ALTERATON I N CD4' T CELLS / CD8' T CELLS RATIOS I N CON A STIMULATED LYMPHOCYTES BY SYNTHETIC POLYMERS. - I N V I T R O EVALUATION -

During ex t racorporea l c i rcu la t ion(EC) such a s hemodialysis, changes i n lymphocytes subpopu- l a t i o n and func t ions have been reported. Dialy- s is membrane e f f e c t s on such changes have been considered. I n t he present study the e f f e c t of syn the t i c polymers on lymphocytes were inves- t i g a t e d i n v i t r o i n terms of changes in T c e l l subpopulation and 1L-2 production. Murine sp l en ic lymphocytes were cultured w i t h

ConA i n t he presence o f g l a s s beads coated with d i f f e r e n t polymers, namely ce l lu lose ace- ta te (CA) , polyvinyle alcohol(PVA) , polyacrylo- nitorile(PAN). Af te r 72 h r s , the expressions of C D 4 and CD8 ant igens on the cu l tured lymphocytes were analyzed by FACSCAN. Fur ther , amounts of IL-2 i n the cu l ture supernatants were quant i f ied by GiJls's method +and compared.

The r a t i o s of CD4 T cells/CD8 T c e l l s were cons tan t ly h i g h e r ( l . l ) i n lymphocytes cu l tured i n presence of various polymers than those i n con t ro l cu l tu re s where no polymer beads were added(0.9). However, i n s ign i f i can t d i f f e r - ence was seen among lymphocytes cu l tured with C A , PVA and PAN. Furthermore, each c e l l cu l tu re produced almost same amounts of IL-2 desp i t e t h e presence and absence of t he polymers(CA 4 3 , PVA 52, FAN 49 and con t ro l 43) .

The present f ind ing suggests these influences on lymphocytes should be taken i n t o consid- e r a t i o n , when p a t i e n t s a r e t r e a t e d by EC. Ayumi Mito, Shun Murabayasi, Tosio Yuta, Chikako -1nabuch;T Kaauya Iwabuchi? and iiazunori Onoe? Dept . of Biomed. ~ n g , * Ins t . of Immunol. s c i . Univers i ty of Hokkaido, Sapporo, Japan


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THERAPEUTIC EFFECT OF HEPATOCYTES ENTRAPPED WITHIN Ca-ALGINATE ON DAMAGED HEPATOCYTES

We have been studying the liver functions in rat hepatocytes entrapped within Ca-alginate for the purpose of developing a hybrid artificial liver. Entrapped hepatocytes have abilities to synthesize and secrete plasma proteins. We examined whether entrapped hepatocytes can secrete soluble factor stimulating liver functions in hepatocytes damaged with D-galactosamine. Ability of tyrosine aminotransferase(TAT) induction, which is a liver-specific function, was decreased by the addition of D-galactosamine in dose dependent manner. Entrapped hepatocytes were co-cultured with the damaged monolayer-cultured hepatocytes. The decreased ability of TAT induction was recovered by the co-culture. Moreover, the ability of TAT 'induction was stimulated by cultivation with conditioned medium prepared from entrapment culture. These results suggest that entrapped hepatocytes synthesize and secrete the factor which stimulate TAT induction. It is regarded as significant that entrapped hepatocytes can supply the factor which increase the abilitles of damaged liver functions. The factor could stimulate the TAT induction in normal hepatocytes. The liver functions of entrapped hepatocytes will be increased by the addition of the factor. It means that volume of reactor containing entrapped hepatocytes can be reduced in hybrid artificlal liver. Purification of the factor is now under way.

Yoshiharu w, Noriko Yoshikawa, Toshihiko Akimoto, and Kiyohito Yagi Faculty of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan

EFFECT OF LEFT HEART ASSIST ON RIGHT VENTRICULAR FUNCTION.

The detrimental effects of left heart bypass (LHBP) on right ventricular (RV) global function are known. To further elucidate the mechanisms of such interventricular relationship, the venous return (VR) to the RV was controlled with a roller pump while varying ratios 3f CHBP were induced via interatrial septa1 and/or transapical left ventricular cannulation. In group A dogs (n=11) RV dp/dt with a catheter tip transducer, and regional myocardial contractile force (MCF) by strain gauges sutured to the RV juxtaseptal (RVJS) and RV free wall (RVFW) were measured. In group B (n=8) the systolic segmental shortening fraction (SSSF) of the interventricular septum(1VS) and the RVFW were measured on 2D-echocardiograms. Stepwise increase of LHBP ratios from 60 to 103% of the VR with either cannulation technique resulting in progressively decreasing LV volumes and LV ejection fraction (EF) induced significant (p c 0.05, Student's "t" test) reduction o f the RV dp/dt, RVMCF,concomitant increase of the RVED dimensions and decreased RVEF. These changes occur mostly at the expense of the I V S and the RVJS regions, where the negative effects are maximal, especially during maximal left ventricular decompression. Jonclusions: LHBP impairs the normal contribution of the LV to global RV function by interfering mainly with the regional contractility of the interventricular septum and the juxtaseptal region of the RV wall. When LHBP ratios of greater than 80-90% of the systemic VR are required to support a patient, biventricular bypass i s recommended.

i Mivamoto. Jack M. Matloff*. Dpt. Cardiovascular Surgery. Kokura Memorial Hospital, Kitakyushu, JAPAN *Cedars Sinai Medical Center, Los Angeles, CA. USA

. .

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216

BIO-HIHETIC SHA ARTIFICIAL MUSCLE: ITS CONCEPT AND ACTUALIZATION

Artificial muscles have been developed through the two kinds of approaches. One is undertaking for molecular reconstruction to mimic the structure of skeletal nuscle, which is one of the most efficient functional actuators a t molecular level. and remains in the basic reseach level. The other is to mimic only functionallu, such as electric motors, hydraulic driven devices, and "new actuators", which include Shape Memory Alloy(SnA~. SHA is applying as actuators of robots, artificial hands/legs, artificial organs, etc. because of direct energy conversion from thermal energy to mechanical Pover without any noise and of Power weight ratio advantage. It has, however. weak points of less actual Power and of control difficulty. The third approach to mimic both structurall~ and func tionally was proposed in this paper. Firstly the artificial sarcomere, which is a structural and functional minimum unit. using SHA wire was developed a s C O ~ P O - nents of the hio-niaetic SHA artificial suscle. The artificial muscle was consisted of the artificial sar- comeres connected in series and/or in parallel. This resulted in longer strokes and Bore powerful. Further- more. some kinds of manipulators were developed using the artificial muscles a s actuators. Push/~ulI action mechanisn to recover the stroke latency by tvo sets of the artifical muscles. so-called antagonists, revealed more excellent performance and controllabilit~ than the ordinary coil spring antago- nistic action mechanism.

Hi toshi HIYAKE Nagaoka Universi ty of Technolos~ Physical Education and Health Care Center Kami tomioka-cho 1603-1, Nagaoka. Japan 940-21

HEMODYNAMIC PARAMETERS INFLUENCING CLINICAL PERFORMANCE OF NOVACOR LEFT VENTRICULAR ASSIST DEVICE

The interrelationships between hemodynamic variables including right ventricular (RV) performance with filling/ejection dynamics of the NOVACOR left ventricular assist system (LVAS) were determined in 10 of 11 patients who received LVAS as a bridge to heart transplant. 8 were successfully transplanted and one is currently supported. Data were obtained intraoperatively, at periodic intervals up to 48 hours post implant and at explant. The hypotheses investigated included: 1. RV performance influences LVAS filling characteristics, 2 . LVAS pump output is influenced by systemic vascular resistance (SVR). During the period of LVAS support (1-107 days), pumping characteristics included a mean filling volume of 56 ml ( 2 4 - 7 0 ) , residual volume of 4.9 ml (1-18), pump rate of 113/min (63-175) and pump output of 5.81/min (2.8-8.2). Average left ventricular pressure of the native heart was 55/10 mmHg.

Multiple regression analysis identified pulmonary vascular resistance (PVR), RV stroke work index (RVSWI) and pulmonary capillary wedge pressure but not RV ejection fraction, pulmonary artery pressure or central venous pressure as the most important correlates with LVAS filling volume. (p(.001,R2=.6) In addition, LVAS pump ou t - put was influenced mainly by RVSWI, PVR and SVR. (p(.001,R2-.8) We conclude that LVAS performance is highly dependent upon RV function and systemic +pulmonary vascular resistances.

Yuji Miyamoto, Robert Kormos, Harvey Borovetz, Thomas Gaisor, Robert Hardesty, Bartley Griffith Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania USA



217 EFFECI'S OF LEFT WNTRICULAR ASSIST DEVICE (LVAD) ON A VENTRICULAR SEPTAZ, PERFCBATION (VSP) MODEL USING AN IN-VITRO ASSIST CIRCULATORY SYST3L

O p e r a t i o n is the last resort to r e s c u e the p a t i e n t who developed VSP c o m p l i c a t i n g acute myocard ia l i n f a r c t i o n w i t h cardiogenic shock. A LVAD ap-pars t o be a powerful ajunct i n this o p e r a t i o n , h o w v e r t h e amounts of e f f e c t i v e n e s s of LVAD on VSP has not been assessd. Therefore, w e e v a l u a t e d hemody- m i c b e n e f i t s of a LVAD an in-vi t ro assist c i r c u l a t o r y sys tem which w a s em- posed w i t h a pair of a i r driven a r t i f ic ia l hearts ( A H ) , mock circulatory system and LVAD. F i r s t , w e made VSP models wiL& various grades o f l e f t ventr icular failure by regulating t h e d r i v i n g pressure o f AH. Then, w e divided them i n two groups ; Nonshock group (BP>SOmmHg,n=l5) and Shock g r o u p (3P<90nmHg,n=l7), and investigated c o m p a r a t i v e l y the hernodynamic effects of LVAD(counterpu1se drive) i n two groups. A s ta t i s t ica l c a n p a r i s o n between t m g r o u p s was mde by a paired Wilcoxon m e t h o d .

I n Nonshock group, t h e mean aortic pressure(Aop-m, 7 7 t 3 - 8 7 4 mtQ) and cardiac o u t p u t (al,3.W.4-5.7d.8 Umin) increased s i g n i f i c a n t l y ( p 0 . 0 1 ) and the left a trial pressure (LAP ,I ?&-&3mHq) ,p~lmonary s y s t e m i c f l o w ratio(Qp/Qs,l.M.3-1.3a.2) and shunt f low(SF, 2.5-10-7-1 .W.9 l/min) decreased s i g n i f i c a n t l y ( p 0 . 0 1 ) . Also i n shock group the Aopm(5%-7%6 mnHg) and CO

(2.84.2-3.5-10.5 l / m m ) increased(p0.01 ),and the LAF'(1h 6-%5 nmHg) ard Qp/Qs(2.1d.1-1.9?0.2) decreased(p0.01) . However t h e SF(3.04.4-3.1?0.4 l/min) did not decreased.

Thus, because t\e SF did not decreased i n t h e Shock group, a LVAE alone did n o t ' x n e f i t and surgical closure of s h u n t has to be done.

1;azumi Mizuquchi, Soichiro Xi'camura, Kanj i Kawacfii , Hironori Whyashi, Ryuichi Morita and Yoshiaki KO\.

L e p e r b e n t o f Surgery 111, N a r a M e d i c a l C o l l e g e , el l0 Shi jo-cho , Sashihra, Nara 634, Japan.

i n a VSP m o d e l u s i n g

219 ADVANTAGE OF THE HYPOTHERMIC SELECTIVE CEREBRAL FERFUSION I N ANEURYSM OF THE AORTIC ARCH

C e r e b r a l damage should be prevented i n t h e s u r - g i c a l c a s e s of aneurysm of t h e a o r t i c a r c h . For t h i s reason , we have used t h e hypothermic s e l e c - t i v e c e r e b r a l p e r f i s i o n (HSCP) s i n c e 1982.

The purpose of t h i s p r e s e n t a t i o n i s t o c l a r i f y t h e p r o t e c t i n g manner from t h e c e r e b r a l damage and i t s r e s u l t s i n such cases.

T h i r t e e n cases of aneurysm of t h e a o r t i c a r c h underwent t h e c o r r e c t i v e o p e r a t i o n i n c l u d i n g t h e r e c o n s t r u c t i o n of t h e branches of t h e a r c h under t h e s u p p o r t of t h e HSCP. The venous d r a i n a g e w a s performed from t h e SVC and t h e I V C , and t h e oxygena ted b lood w a s poured i n t o t h e l e f t femora l a r te ry(50ml /Kg/min) , t h e b r a c h i o c e p h a l i c a r t e r y (3ml/Kg/min) and t h e l e f t common c a r o t i d a r t e r y (3ml/Kg/min) under t h e g e n e r a l deep hypothermia of 20 "c. The a r t e r i a l p e r f u s i o n p r e s s u r e w a s main ta ined a t 50mmHg.

Seven of 13 cases (54%) were s u r v i v e d a f t e r t h e s u r g e r y , and t h e major causes of d e a t h w e r e r e n a l f a i l u r e i n 3 cases, mass ive b l e e d i n g i n 2 and LOS i n 1. The t r a n s i e n t l e f t hemipleg ia w a s s e e n i n only 1 c a s e . Both t h e c e r e b r a l oxygen consumption and t h e c e r e b r a l l a c t a t e e x t r a c t i o n d u r i n g t h e I1SCP were minimal ly main ta ined i n t h e s u r v i v e d uses .

I n conclus ion . t h e hypothermic s e l e c t i v e cere- b r a l p e r f u s i o n i s a s a f e assist c i r c u l a t i o n i n che t r e a t m e n t of aneurysm of t h e a o r t i c a r c h .

LCetsuo Mizutan i , Kazuhisa Shikano, I s a o Yada, I l i r o s h i Yuasa, Minoru Kusagawa ')apartment of Thorac ic and Card iovascular Surgery , Ifie U n i v e r s i t y School of Medicine, Tsu, Japan

218 EVALUATION STUDIES OF SHORT AND LONG TERM EFFECTS OF PLASMA EXCHANGE ON VARIOUS RENAL DISEASES

change (PE) were e v a l u a t e d on v a r i o u s 23 r e n a l d i s e a s e s ( SLE 7, MRA 3 , RPGN 5 ( g o o d p a s t u r e ' s syndrome 1 ) , MPGN 2 , membranous GN wi th r e n a l v e i n thrombosis 1 , pr imary a m y l o i d o s i s 1 and myeloma k idney 4 ( Bence-Jones type 3 ) ) .

PE was performed on pr imary and secondary G N combined w i t h s t e r o i d a n d / o r immuno-suppressant and a n t i - c o a g u l a n t a g e n t , and on myeloma and amy- l o i d o s i s w i t h chemotherpies and d i m e t h y l s u l f o x i d e . 2-3L plasma was exchanged o r t r e a t e d by each s i n - g l e membrane PEs o r double f i l t r a t i o n PEs. 3-13 t i m e s PEs were achieved on each p a t i e n t s .

2-3 months s h o r t term e f f e c t of PE on r e n a l f u n c t i o n s were e v a l u a t e d . Ccr were s i g n i f i c a n t l y improved i n a l l 7 SLE, 1 of MFlA, 2 of RPGN, 1 of MPGN and membranous G N . Other 2 of RPGN and 1 of I4.PCN needed HD. I n a m y l o i d o s i s , Ccr was i n c r e a s e d b u t n e p h r o t i c syndrome was worsened. I n t h e PE e f f e c t i v e 4 of SLE and 1 of RPGN, p r o t e i n u r i a was i n c r e a s e d t r a n s i e n t l y . A l l 4 myeloma were t r e a t e d by HD i n i t i a l l y , b u t i n 3 of them, HD could be d i s c o n t i n u e d af ter PE, and u r i n e volume was i n - c r e a s e d i n another one.

I n 3-27 months, 2 of SLE, 1 of MPGN, 2 of myeloma and amyloidos is d i e d of s e p s i s . I n l o n g te rm o b s e r v a t i o n ( mean 49.3 months 1, HD were i n i t i a t e d i n 4 of t h e PE e f f e c t i v e 12 l i v i n g pa- t i e n t s ( RPGN 2 , membranous GN l , myeloma l ) .

The s h o r t and l o n g term e f f e c t s of plasma ex-

Masao Hizune, H. Hasegawa, T . Tsuzuki , H. Hasegawa T . F L j i s h i r o , T. Oeawa and S. Kawashima I n t e r n . Ned. Fuj i ta -gakuen H e a l t h Univ. Toyoake, Aichi , Japan

220 INFECTION AND THROMBOSIS: PREFERENTIAL ATTACHMENT OF BACTERIA ON ADHERENT THROMBI

Thrombosis and infection are the two most common problems associared with implanted prosthetic devices. A possible association between infection and thrombosis has been speculated but not yet confirmed by experimental data. This report wiil demonstrate that cenain bacteria may preferentially adhere to fibrin formed at the blood- material interface and may, in this manner, contribute to the process which results in sustained infection.

Cultures of Pseudomonas aeruginosa or Staphylococcus epidermidis maintained in Trypticase Soy Broth were added to fresh bovine heparinized (5 U/ml) blood in vitro. When necessary, bacteria were also labelled with Trans3sS. A test chamber was used to study the interaction of bacteria with test surfaces under static condition and a flow chamber was used to evaluate bacterial adhesion under laminar or non-laminar flow. Test surfaces (glass, polystyrene. glass coated with Biomer) were used either as such (control) or treated with various plasma proteins. In some experiments, fresh non heparinized bovine blood was allowed to clot under controlled conditions to obtain surfaces with adherent thrombi. Blood in which bacteria or bacteria plus gentamicin were added was then incubated (or circulated) for a predetermined time (3-24 hours) at 37 C and 90% RH. At the end of this incubation, test surfaces were rinsed free of non-adherent bacteria as well as blood components, fixed with 2% buffered glumaldehyde and either stained and examined under light microscope or critical point dried and processed for scanning electron microscopy. Surfaces with 35.7 labelled bacteria were analyzed either by scintillation counting or auloradiography. It was noted that bacteria Dreferendallv attached in large numbers to areas of a test surface where ihrombus was adherent. Preliminary studies also suggest that this preferential attachment was more uronounced in areas where a greater number of platelets were adherent. These observations strongly suggest that thrombus may serve as a nidus for pathogenic organisms.

S.F. Mohammad, M.M. Ali. G.L. Burns and D.B. Olsen Artificial Heart Res Laboratory. Univ of Utah, Salt Lake City, Utah, USA


338 ABSTRACTS OF THE VIZth WORLD CONGRESS

221 THROMBOGENESIS IN BLOOD PUMPS: HEMATOLOGIC CHANGES IN CALVES WITH PARACORPOREAL LEFI VENTRICULAR ASSIST DEVICE (LVAD)

Thrombogenesis caused by blood pumps was investigated in calves receiving a series of paracorporeal LVADs. In this animal model, the uptake and return cannulae placed in the left atrium and the descending aorta respectively were connected to a pneumatically driven 85 or 100 cc LVAD (with Medtronic-Hall mechanical valves) external to the chest wall. Circulation of blood through each LVAD ranged from 6 hrs to 4 days. The blood circulated through the LVADs @ 4 Wmin. Animals were heparinized (5000 v) prior to each LVAD change and blood was drawn at frequent intervals. The following parameters were monitored: Prothrombin Time, Activated Partial Thromboplastin Time; Platelet, WBC and RBC counts; Plasma Free Hemoglobin (T'FHb); Platelet aggregation; Factors V. X, XII. Fibrinogen, Antithrombin III; Fibrinogen /Fibrin Degradation Products (FDP) and blood chemisq.

No change in RBC count, a gradual decrease in WBC and a slight fluctuation in platelet count was observed. PFHb stayed below 3 mg/dl. Factor XI1 concentration increased initially and then returned to the baseline level every time a new LVAD was connected to the same animal. Factors V and X increased gradually throughout the study and independent of the ventricle changes in each animal. The FDP concentration stayed below the detection limits in all animals lhroughout the study. No change in circulating levels of Fibrinogen. AT 111, Sorbitol Dehydrogenase or total protein Concentration was observed. Serum LDH and SGOT gradually increased during the first two ventricle changes in each animal leveling off thereafter.

The advantage of this ex vivo animal model included i) evaluation of short (minutes) and longtenn (days) effects. and ii) evaluation of the effect of a number of LVADs on the same animal. The observations suggested that a number of hematological parameters change as a result of the exposure of blood to a prosthetic device. No detectable increase in FDP concentration suggests that it may not be a useful marker for thromboembolism in a bovine model.

S.F. Mohammad, G. Pantalos, S. Sanossian, K. Solen, G. Bums, L. Reynolds and D.B. Olsen. Univ. of Utah, Salt Lake City, Brigham Young Univ, Provo and Univ. of Illinois, Chicago, USA

222 IMPROVED HEMOCOMPATIBKITY OF POLYMERS TREATED WITH A COMPLEX OF ALBUMIN-IMMUNOGLOBULIN G

Efforts to develop hernocompatible polymers include modification of blood contacting surfaces with anticoagulant or antiplatelet agents or passivation with plasma proteins. particularly albumin. Studies reported from this laboratory in the past have shown that cenain surfaces pretreated with a naturally occuring complex of alb-IgG become relatively more hemocompatible (reduced platelet adhesion, minimal thrombus) when compared with untreated (control) or surfaces treated with albumin alone. Since adsorbed proteins, including alb-IgG desorb rapidly when exposed to circulating blood, alb-IgG was immobCid on glass or Biomer as follows: 2 mg/ml solution of bovine IgG was crosslinked wilh glutaraldehyde on the test surface. Crosslinked IgG was then treated with mercaptoethanol and incubated with a solution of albumin (5 mg/ml, previously reduced with rnercaptoethanol) under conditions that allowed reassociation of &sulfide bridges beween IgG and albumin.

Alb-IgG immobilized on glass or Biomer by the above method showed considerable reduction in the adhesion of Illln-platelets in circulating blood in vitro. Under identical experimental conditions, untreated (conuol) or surfaces with crosslinked albumin alone were not as effective in reducing the adhesion of platelets. A significantly greater number of platelets adhered on surfaces with crosslinked IgG. These observations suggest that immobilization of albumin-IgG may have a greater promise in improving the hemocompatibility of polymeric surfaces.

S.F. Mohammad, S.W. Kim and D.B. Olsen Dept of Phannaceutics and Artificial Heart Research Laboratory, Univ of Utah. Salt Lake City, Utah, USA

Since a few years, our group has proposed an alternative nnde of pmping blood inside the body.

(Xlr device is a non centrifugal, valveless, low speed rotary p q , electrically powered, based on Wankel engine principle.

We developped an inplantable electrical actuator resulting in a coqact, sealed mtor-pq unit with electrical and mgnetic crrnponents insulated frm fluids.

The results in the f low curve and in the pqing action show sene c m n points but also s m basic differences compared to classical pulsatile p q s or centrifugal p q s .

The blood caning fran the atrim follows a continuous nwvemmt without any stop Elow but with variations creating pulsatility. Ejection and filling of the p"p are simlca- neous. It is always an active filling. Hydraulic efficiewy depends on clearance in the pimping chamber and outlet port pressure. A 60 cc device allows flows up to E-9 liters. lhe inplantable mtor is cyclindrical in shape, has a mderate wight (490 grams) and presents a good efficiency (32 % for a rotary speed of 90 'pm against a man aortic pressure of 150 m of Hg).

We conclude that our device could be proposed after further experirrental studies, as an LVAD for short term assistance with a good pranise for pemnent application.

JR. MontiPs, T. Mesana, P. Hwlik, J. Trinkl, JL. h n c k , B. Candelon. Labratoire de Recherches aimrgicales - brseille.



225

221

AH?. HOU'IROYIIIL CYTOPLASNIC AUTOhNTltlODlBS M D RERAL PURCTlOl IW IUlOPATHlC CRgSCEllTlC GLOIIERULONBFHRITIS TREATED BY PLASHA EXCHANGE AND STBROID PULSB.

Anti-neulropbil cyloplasnic aubantibodies (AWCA) have ken found in p a t l e n t s r i t b systemic vascul i t is and/or crescentic glonerulonephritis (GII). In this paper re a n a l y a the behaviour of the Serum levels of A K A , renal function and hislologic features in a 21 yrs old, malt, patient with idiopathic crescentic GW treated by plasma-elchange (PE) and 6- methyl prednisolone 16 mp) pulses. The onset of the disease was abrupt, nith serum cr-eatinine rising to 1.9 Ogldl in L reeks. The Kidney biopsy Shored diffuse crescentic and necrotizlng GN r i t b f ibrin deposits In Bowman's spacc. Hlgh serum levels of ARCA were dctected by immuno iiiiorescence microscopy (IF) dnd by E L M (Palk dnd Jmnette , lancet, 19RU), expressed a s ELlSA units [ IU I ; dnti GBH dnLlhdleS w e r ia l found. A coabinrtl iherapy 11th intensive PE and 6 - u p pulses (1 g/day for 3 days) x a s slarted. is Pi3 sessions ?ere done in b reeks and prednisone p/2 mg/Ig b.?,) ras added. The innunological and clinical dab a t t b e beginning ( A ) , E L the m d of PE cycle (Bj and d!ter a ; sontbs follor up period, IC) are s u o n a r i r e d a s follors:

. . .. . . . .... ..... . -. . . -. .. . . .

A B C A K A ill;) ,Ii [I) -.

A K A (EU n.v.t 0.100) 1.011 O.M9 0 . 0 6 a swum crcai . mg/Cl 4.9 1.6 1 . 3

111 : perini ic lerr pattern.

segmi.n;a I g l o n r r u l d r sc lrrohydi inos is without s u n s of rclivlty. The Lrealment with PE and 6 np pulses indlicrd a dramatic inpravcmcni af renal funtl ion and hl - lo log ic frdtures corr t idtro wilt1 the lIQrPdiildt1011 01 seruu ifvt!: V! hNCI Thear m u l l s are . r i kttplnc r ~ l h LI lc dcttral viers by s o w Authors rho hyplhesin t h a t vascul i t is and crescentic G K could Ix 001 only aSSWldled but also aediated by serum AWCA.

I.. No:,coni, R ?uLcinl, A. Pdsquarlclio, 6. Paleologu, R. Caprioli, P. A S i n i c o I , 1 C I D ~ I . Blv . Hefrologica, Spedali Riunit i S. Chiara, Pira, I Div. #PfrQiDglCa, Osy S. Carlo Horrameo, Hilano, Italy.

. - . . ~ . ... . . ..

1 Second kidney blopsy, [ w f o r n r d after the ?E cycle, shored only

NOISE LEVEL AND PERCEPTION OF THE CLOSING CLICK AFTER VALVE REPLACEMENT WITH ST.JUDE

AND BJORK SHILEY MONOSTRUT PROSTHESES The metallic click generated by the closure of mechanical

prostheses may severely bother patients, but the sound energy and extent of complaints after implantation is not known. In 62 patients after valve replacement with St. Jude Medical (SJM) (n=35) and Bjark Shiley Monostrut (BSM) (n=27) prostheses the sound energy was recorded with a calibrated noise level analyzer at 5, 10 and 100 cm distance to the patient and correllated to their complaints. At a distance of 1 m the BSM valves produced a

significantly higher sound pressure with 30.525 db(A) compared to the SJM valves with 24.124 db(A) (p=O.OOOl), whereas there was no difference at shorter distances. After splitting into kequency bands the highest sound pressure was observed in the high frequency ranges (8 to 16 kHz) which represent the metallic click The BSM valves produced higher sound pressures in all ranges. 71 % of the patients were aware of the noise generated by the valve, 20% had sleeping disturbances and 26% would prefer a more silent valve type. 12 of 27 patients with BSM valves, whereas only 4 of 35 patients with SJM valves whished to have a less noisy valve type (Chi square p=0.003). In patients who could hear their valve the sound amplitude was higher (11.524 db(A)) then in patients who could not (9.124 db(A)) (p=0.04). 9 of 27 (BSM) versus 3 of 35 (SJM) the clicking caused sleeping disturbances (p=O.Ol) and 85% of BSM versus 60%of SJM patients could hear their valve ( ~ 4 . 0 3 ) The noise level of mechanical heart valves should be

considered before selection of a prosthesis, because valves with a higher sound pressure of the closing click cause more complaints. A. Moritz, G. Kobinia, U. Steinseifer, H. Wolters, H.

Keul, K. Neuwirth-Riedl, G.Griinbacher, E. Wolner University of Vienna, General Hospital Klagenfurt Austria R.WTH Aachen FRG

226 COMPARISON BETWEEN I N T E R M I T T E N T AND CONTINUOUS HEMOPURIFICATION I N TERMS OF THE INFLUENCE O N 02-MICROGLOBULIN KINETICS

We i n v e s t i g a t e d [>2-mic rog lobu l in ((12-m) k i n e t i c s d u r i n g a n ex tended p e r i o d , a p p l y i n g a ma themat i ca l model t o a p a t i e n t w i t h c h r o n i c r e n a l f a i l u r e on e i t h e r i n t e r m i t t e n t ( r e g u l a r HD o r HDF) o r con- t i n u o u s (CAPD, CAVH or o t h e r forms o f wea rab le a r t i f i c i a l k i d n e y ) h e m o p u r i f i c a t i o n . The pu rpose o f t h i s i n v e s t i g a t i o n i s t o c l a r i f y t h e l i m i t t o which plasmaG2-m c o n c e n t r a t i o n c o u l d be lowered by e i t h e r form of t h e t r e a t m e n t .

The r e s u l t s i n d i c a t e d t h a t when p a t i e n t s w i t h p r e - t r e a t m e n t p l a sma32-m l e v e l o f 6 0 , 40 and 2 0 mg/L were s w i t c h e d from a c o n v e n t i o n a l HD t o a h i g h l y e f f i c i e n t HDF (C.2-m c l e a r a n c e of 40 mll m i n ) , t h e lower ing l i m i t w a s 39 , 31 and 18 mg/L, r e s p e c t i v e l y .

The r e s u l t s a l s o i n d i c a t e d t h a t e v e n when swi t ched from a c o n v e n t i o n a l HD t o CAPD, t h e d e c r e a s e of p l a s m a r 2-m l e v e l is minimal because of t h e ex t r eme ly smallTj2-m c l e a r a n c e o f 0 .66 m l / m i n by t h e p e r i t o n e a l membrane. However, we e s t i m a t e d t h a t p l a smac2-m l e v e l c o u l d be lowered from 60 mg/L on a r e g u l a r HD t o 25 .7 mg/L on CAVH or o t h e r forms o f w e a r a b l e a r t i f i c i a l k i d n e y , p r o v i d e d t h a t t h e y o f f e r a body f l u i d r ep lacemen t r a t e o f 8 L/day and 3.3 ml/min o f 2-m c l e a r a n c e . I t s h o u l d b e n o t e d t h a t t h e plasma(:Z-m c o n c e n t r a t i o n c o u l d be lowered o n l y from 60 mg/L t o abou t 3 5 mg/L, even i f b e i n g t r e a t e d w i t h a maximally e f f i c i e n t HDF, i n which the?,Z-m c l e a r a n c e i s i n c r e a s e d up t o 100 ml/min.

Thus, we conc luded t h a t t h e most a p p e a r e n t d e c r e a s e o f plasma 1: 2-m l e v e l would be a t t a i n e d by c o n t i n u o u s h e m o p & i f i c a t i o n o t h e r t han CAPD, namely. CAVH o r o t h e r fo rmes of w e a r a b l e a r t i f i c i a l k idney .

H i rovuk i M o r i t a . T a k a h i r o S h i n z a t o , I c h i r o T a k a i , Yosh i ro F u j i t a , H i royuk i Kobayakawa and Ken j i Maeda The Branch H o s p i t a l Nagoya U n i v e r s i t y School o f Medicine

228 AUTOGENEOUS ARTERIAL GRAFTS CREATED BY WRAPPING OF DILATED VEINS WITH REABSORBABLE CONSTRICTIVE MESH TUBES A biologic, arterial graft can be created if dilated, otherwise

unusable veins are wrapped with a consnictive mesh tube. We wanted to proove whether a reabsorbable cosmctive tube creates a well dimensioned vascular graft by induction of neo arterial wall growth. In 8 sheeps a 5 cm segment of the carotid arteries was

resected and the external jugular vein was inserted as a tubular graft. The vein was either wrapped with a polydioxanon (PDS) reinforced polyglactin (VicrylR) mesh (n=4), a Vicryl mesh (n=4) or a Dacron mesh tube (n=3) to achieve a diameter reduction to 7 mm or was used without reinforcement (n=3). At angiography after 6 months the native veins had a

diameter of 19 mm (15-22). the VicrylR reinforced veins measured 9.4 (8.5-10) mm but 3 of 4 developed aneurysmatic dilatations at sites of valve sinuses with a mean diameter of 19 (15-21) mm. PDS reinforced veins measured 7.4 mm (7.1-7.9). 2 of 4 had minor anastomotic aneurysms of 13 and 16 mm, but as those were already present after 2 months, a rupture of the PDS reinforcement must be anticipated. The 2 remaining grafts were virtually indistinguishable from the native artery. The Dacron tubes reduced the vein size most reliably to 7.6 (7.5-7.9) mm but showed some narrowing at the anastomoses (PDS 7.233.4 Dacron 6.1M.4 p=0.016). PDS wrapping reduced the maximal graft diameter to 10.9k4 mm as compared to the native vein of 18.723.5 ( ~ 3 . 0 4 8 ) . Reabsorbable meshes can reduce the diameter of a venous

graft by sufficient strenghtening of the vessel wall. PDS reinforcement needs further technical refinement to prevent early local dilatation, Dacron seems to be a saver alternative in this respect but tends to create anastomotic narrowing. A. Moritz, F. Grabenwoger, A. Windisch, R. Horvath, U.

Windberger, U. Losert, E. Wolner II. Chirurgische Universitatsklinik Wien, Vienna Austria



229

231

PLATELET FUNCTION VS HEMoLySIS PiuWl~~ms mF?

Artificial bloodpumps -cause thromboembolism by two mechanisms: Mechanical trauina and complex immunologicai and cellular reactions, both involving blood plate1ets.Main goal of this study was to find a decent parameter of platelet reaction besides the commonly used indicator of cell damage, plasma free hemoglobin (PHb). 7 different rotary blood pumps were tested in a mock circulation with a priming 1 against 150 mmHg. Fresh whole blood from cattle was taken using standardized technique. Flow, pressure, temperature, blood gases, glucose level and whole blood count were controlled. Our test parameters were PHb, thromboxane B2 (TXBZ), whole blood aggregometry and morphology (SEMI. Each test run was carried out for 180 min. For data analysis new indices for hemolysis and thromboxane release were used. Our data are satisfactory reproducable and allow a ranking of the pumps concerning mechanical trauma (PHb) and surface-induced platelet activation (TXBZ). The amount of TX-production showed good correlation with the material, not with the mechanical trauma.

IN - VITRO TESTING OF BILKIDPUMPS

volume of 2 1 and a flow of 5

M.R.Miiller, A-Wohlfahrt, H.Schima, J.Schaberth, U.Losert, E.Wolner 2nd Dept..of Surgery and Ludwig Boltzmm Institute, University of Vienna, Austria

THE EFFECTS OF EXTRACORPOREAL CIRCULATION ON POST- OPERATIVE RENAL FUNCTION USING MEMBRANE OXYGENATOR -7-GT AS A NEW MARKER-

This s tudy i n v e s t i g a t e s t h e c l i n i c a l e v a l u a t i o n of t h e r e l a t i o n s h i p s between t h e u r i n a r y volume dur ing e x t r a c o r p o r e a l c i r c u l a t i o n ( E C C ) and p o s t o p e r a t i v e r e n a l f u n c t i o n us ing a membrane-oxygen- a t o r . y-glutamyl t r a n s f e r a s e (I-GT, which is a enzyme, r e l e a s i n g mainly from t h e brush border of r e n a l t u b u l e s ) , 62-Microglobulin ( b z - m , low molecu- l a r p r o t e i n and thought t o be a e x c e l l e n t marker of t u b u l a r f u n c t i o n ) , c r e a t i n i n e - c l e a r a n c e ( C c r ) and o t h e r convent iona l parameters i n d i c a t i n g main- l y r e n a l t u b u l a r f u n c t i o n s , were measured i n 30 p a t i e n t s wi th c a r d i a c d i s e a s e . They were d i v i d e d i n t o t h r e e groups accord ing t o u r i n a r y volume(UV) dur ing ECC:Groupl, 7 p a t i e n t s , UV<5ml/min;Group2, 8 p a t i e n t s , 5<UV<lOml/min;Group3, 15 p a t i e n t s l O m l /min<UV. Urinary I-GT i n d e x ( u r i n a r y 7 -GT/urinary C r ) l e v e l s had a p a t t e r n o f change similar t o t h a t o f b2-m. Urinary ',-GT index l e v e l s i n Groupl were e l e v a t e d t o s i g n i f i c a n t l y (~(0.01) higher leve l ; a t t h e e a r l y s t a g e of ECC than Group3 and a l s o cont inued t o show h i g h e r l e v e l s u n t i l t h e t h l r d P o s t o p e r a t i v e day. Futherrnore t h e most r a p i d recovery of C c r was s e e n i n Group3.

t u b u l a r dysfunct ion , t h a t r e n a l damage is g r e a t e r and more prolonged i n Groupl & 2 than i n ~ ~ 0 ~ ~ 3 , and t h a t t u b u l a r dysfunct ion depends on u r i n a r y volume dur ing ECC. I n conclus ion , i n order to n t a i n t h e t u b u l a r f u n c t i o n , we t h i n k i t is very impor tan t t o Secure t h e u r i n a r y volume a t l e a s t Over lOml/min from t h e e a r l y s t a g e o f ECC.

Atsubumi Murakami,Makoto Funami,Masahirc Aiba, Noboru Yamamoto,Kouich Inoue, T o s h i h i r o Takaba Department of Surgery , F a c u l t y of Medicine, Shows U n i v e r s i t y , Tokyo,Japan

This s tudy showed t h a t 1-GT is a good marker of

230 HYDROXYAF'ATITE TRACHEAL -IS EDIUXUC WG L A s W l R F a D ~ r J s r n ~ I R R A D y L T I c N m

Tracheal prosthesis were developed with dense hydroxyapatite tubes in combination with YAG laser irradiation. The lateral irradiation probe emmitting laser in

cicumferentialdirection was applied to destroy selectively mucous secreting cells in the inner membrane circumferentially and uniformly prior to implantaion. The appropriate surface 'temperature which was found to be 6O0S by histological inspection in preceding experiments was realized by monitoring with a thennospot sensor. The tubes implanted in 6 rabbits were fixed by ligation and those having suture holes at the both ends implanted in 13 dogs were sutured tightly to the trachea. The tube was succesfully adhered tightly to the

inner membrane of the trachea in a rabbit pretreated with YAG laser irradiation In case of dogs, the tubes formed no granulation tissues showing few infiltration of inflammatory cells but failed in adhering to the trachea. A dog having the prosthesis lives for more than 17 months up to date without dislocation. However, without pretreatment of YAG laser irradiation, all the tubes were dislocated and rejected because of purulent mumus accumulation The hydroxyapatite tube can be used as a

tracheal access in combination with pretreatment of YAG laser irradiation to the inner membrane.

Katsuki Muneoka, Takayuki Tsuj i, Hideki Aoki, Yoshiharu Shin and Tatsuo Togawa Institute for Medical and Dental Engineering, Tokyo Medical and Dental University, Tokyo, Japan

232 EVALUATION OF CARDIAC FUNCTION DURING HEMODIALYSIS I N DIABETIC NEPHROPATHY AS REFLECTED I N DOUBLE PRODUCT, STROKE WORK I N D E X , SYSTEMIC VASCULAR RESISTANCE AND pnOz

C i r c u l a t o r y f a i l u r e occurs more f r e q u e n t l y d u r i n g hemodia lys i s (HD) i n d i a b e t i c p a t i e n t s than i n p a t i e n t s w i t h c h r o n i c r e n a l fa i lure(CRF) due t o o t h e r causes . C a r d i a c f u n c t i o n measured by a Swan- Ganz c a t h e t e r and ps02 d u r i n g HD of 1 3 d i a b e t i c CRF pat ients(DN group) were compared wi th t h o s e of 18 non-d iabe t ic CRF patients(non-DN group) . Double product(DP, oxygen consumption i n d e x ) , s t r o k e work index(SW1, LV c o n t r a c t i l i t y ) and sys temic v a s c u l a r r e s i s t a n c e index(SVR1, v a s c u l a r response) were e v a l u a t e d p r i o r t o and each hour a f t e r s t a r t i n g HD, and p a O ~ w a s measured p r i o r t o and a t ending HD. R e s u l t s : 1)The r e g r e s s i o n c o e f f i c i e n t f o r t h e r a t e of v a r i a t i o n i n SWI(%SWI) t o t h e r a t e of v a r i a t i o n i n DP(%DP) w a s s m a l l e r i n t h e DN g r o u p ( 0 . 6 6 ~ ~ . 1 .02) , and t h e s e i n d i c e s c o r r e l a t e d h i g h l y i n both groups . 2)The r e g r e s s i o n c o e f f i c i e n t f o r t h e r a t e of v a r i a t i o n i n SVRI(%SVRI) t o %SWI was p o s i t i v e i n t h e DN group, and d i f f e r e d ( p < 0 . 0 5 ) between groups(+0.45vs.-0.26). These i n d i c e s c o r r e l a t e d s i g n i f i c a n t l y i n b o t h groups. 3)The r e g r e s s i o n co- e f f i c i e n t f o r %DP t o t h e v a r i a t i o n i n paOz (4p.O~) w a s n e g a t i v e i n t h e DN group, and d i f f e r e d ( p c 0 . 0 5 ) between groups(-0.39vs.+0.46). I n o u r p r e v i o u s r e p o r t (25 th JSAO) , a h i g h i n v e r s e c o r r e l a t i o n between %SWI and f l u i d removal d u r i n g HD was demonstrated. Our p r e s e n t f i n d i n g s sugges ted t h a t d u r i n g HD t h e DN group had l e s s e f f e c t i v e supply and u t i l i z a t i o n of oxygen and an impai red com- pensa tory mechanism f o r d e c r e a s e s i n c a r d i a c func- t i o n a s s o c i a t e d w i t h i n c r e a s e d f l u i d removal. Tsuneo Murasawa, Yoichi ro Hanyuda, Yoshiyuki Honda, Osamu Suzuki , Yukio Ueda and Fumio Hara Dept. of I n t . Med., Hosp. 2, Nippon Medical School, Kawasaki, Kanagawa, Japan

Artificial Organs. Voi. 13, No. 4, 1989

233

235


l i n t . , \ i ng ress ' ISLO, !< ;o t i l , A b s t r a c t s , p . 1 6 3 , 1 9 8 3 . 2 / ! . l u s i l Z.: S i i n u l a t i o n s o f sorne p a t t i o p h y - s i c ' l3 'j 1 I: s i n t h e c a r r: i o p u I rn Lina r y c i r c u 1 a - t i o n . I . C o n f e r e n c e o f S o c . A c a d e m i e s , P r a g u e , P t u c z e d i n g s 5 , 2 5 5 , 1 9 9 7 . 3 / X u s i l 2.: A l s o r i t h r n o f t h e t o t a l a c t i - r i c i a l h e a r t ( T t \ t i ) . Zontou t e r inoc!el v e r s - i c n , X i ' . Z o n G r c s s ESdO, P r a g u e , . l S s t r a c t s , p . 13, 173il .

M u s i l J a n , S u r g i c a l D e p a r t - m e n t a t id ; i i ~ s p i t a l , Z h a r l e s U n i v z r s i t y , P r a g u e , C z e c h o s l o v a k i a .

PLASNAPHERESIS (PP): ITS CLINICAL AND IMMUNOLOGICAL DIPACT IN CRYOGLOBULINTNU (CG)

PP is the mainstay of treatment in CG unre- sponsive to conventional therapy. While the goal of PP is primarily solute removal, cellular immunity contributes importantly in disease activity and prognosis.

Four CG patients with skin lesions (n=4) and peripheral neuropathy (n=l) treated by plasma exchange (PE) or cryofiltration (CF) with the Asahi APO6M were evaluated. Clinical assessments as well as immunological assessments were studied. Cellular studies consisted of mononuclear cell (MN) transformation, granulocyte chemotaxis, and monocyte phagocytosis. Cryogels and plasmas were also evaluated for modulation of normal MN functions in vitro.

Skin lesions were improved in all patients, but peripheral neuropathy did not change. One patient treated by PE had infections three times in 2 years. MN proliferation showed increases pre to post treatment (10,743+4,637 vs 18,506+ 9,651 cpm). Plasmas and cryogels at protein concentrations comparable to the patient plasmas had a suppressive effect on normal MN proliferation and granulocyte chemotaxis.

These data show that PP can stabilize clinical symptoms and improve immunological functions. Conventional PP caused hypogammaglobulinmia and early filter plugging also in CP. To overcome these problems, CF using new high capacity cryoglobulin filter is under investigation.

Shin'i Na anuma, Paul S. Malchesky, Koji Sawada, Ecilj Zbtrowski, Anna P . Koo, Yukihiko Nose, Cleveland Clinic Foundation, Cleveland, Ohio, USA

234

236

341

DETERtllNATiON OF BlOCOnPATlBlLlTV OF POLYURETHANE (PU) SURFACES IN DYNAMIC EX-VIVO STUDIES

The aim of th is stub+ i s to investigate the biocompatibilitq of the segmenteo polyurethane i PU) biomaterials by a novel jtimulus-response technique. Both in -v i t ro and ex-vivo studies were performed by using rediolabelled albumin (99mT~-HSA) is a tracer

In in -v t t ro s!udie serum physiologic solution was r-eLirculatad through the sorption co lumn containing PU beads Labelled protein solution was puls injected at the inlet, than the i-espunje wet-e rneasured by a w-nrna scinti l lator Animal ( ra ts ) erperiments have been also carried out to confirm the stimulus- tespurise technique ex-vivo. The b l w l from the ra! was recirculated through a s imi lar column used in in -v i t ro studies. Fcadiolabelled Bovine Serum Albumin (99mTc-EiS41 was puls injected into the inlet and the distribution of albumin throughout the system (column+animal) was continuously observed bv a gamma camera which was placed top of exoerimental set-up and the animal The "0" curves obtained i n in -v i t ro studies were used to represent the albumin adsorption &sorption phenomena. The equi l ibr ium concentration 01 albumin was obtained from these curves was 0.06~k0.0041 W( Basis on total in]ection)/cm 2 of PU. The distribution curves obtained i n ex- vivo tests were us& to &fine the dynamic adsorption of albumin. The obtained value was 0.OS3t0.0024X(Basis on total injection)/cm 2 oi PU.

These results cuncluded as, the i n -v i t ro test findings can be used to pre-estimate the ex-vivo behaviour of the biomaterials to be considered.

M. MUTLU*,A.K. Pi$KiN**,M.T ERCAtl***. E. fiSKlN* * Chemical Engineering Department ** Virology and Molecular Biology Department *** Nuclear Medicine Department Hacettepe University, Beytepe Campus, 06532 Ankara, TURKEY

THERHM. EFFECT ON HunoRAL AND CELLULAR SYSTm: IN VITRO STUDY

There is little information available on effects of heat dissipation by implantable, mechanical ventricular assist systems (VAS) on lymphocyte functions and immunological surveil- lance system.

Plasma/serum and cellular components of human and calf blood were exposed to heat separately. The combination of the temperature of 37, 40, 42, 44, 47, 50 and 52°C and the exposure time of 5, 10, 15, 30 and 60 min were selected. The study consisted of survival rate (Trypan blue dye exclusion test), morphological evaluation using electron microscopy, lymphocyte proliferation to mitogens and the effects of heated serum on normal lymphocyte functions.

The results indicated that even brief heat exposure (47"C, 15 min) activated the complement system through both alternative (C3a) and classical pathways (C4a). Heated serum had an inhibitory effect on normal lymphocyte proliferation [16,730+8.483 cpm ( 5 2 " C , 60 min) vs 50,494k 19,473 cpm (37"C), p<0.051. Although lymphocyte retained viability at 44'C, 60 min (91.4t 3.2%), its function had already deteriorated irreversib- ly (6.1% of control value). Species differences in heat tolerance were also noted between human and calf.

These data suggested that heat (>40"C) can directly affect humoral and cellular immune system and may compromise local defense mechanisms to infection and tissue healing.

Shinji Naganma, Hiroaki Harasaki, Denise Zona, Tomoaki Jikuya, Junichi Utoh, Yukihiko Nos&, Cleveland Clinic Foundation, Cleveland, Ohio, USA

Arrifciol Organs, Vol . 13, No. 4, 1989


237 NEW SEQUENTIAL SYNCHRCNIZED D R I V I N G SYSTEM CF 238 INTRAACRTIC BALLCCN PUMPING AND LEFT VENTRICULAR ASSIST DEVICE: INFLUENCE CN ENDCCARDIAL V I A B I L I T Y M T I C AND RENAL BLCCD FLCW I N THEIR CCMBINATICN

v e n t r i c u l a r a s s i s t device (LVAD) have shown remark- a b l e progress i n d i v i d u a l l y , b u t , how t o combine them is s t i l l unknown. New s e q u e n t i a l synchro-- n ized d r i v i n g system was developed t o c o n t r o l concomitant use o f IABP and LVAD, and t h e n , i t s hemodynamic e f f e c t i v e n e s s was eva lua ted i n swine, e s p e c i a l l y on endocardia1 v i a b i l i t y r a t i o (EVR) and r e n a l b lood f low. pass pump-delay d iv ide system; PBP-DDS) made it p o s s i b l e t o change t h e d r i v i n g phase o f IABP and LVAD e a s i l y . I n 1 2 swine, IABP and LVAE were s e t up and t h e s e devices were dr iven i n t h e fo l lowing 5 modes wi th thePBP-DDS; mode I.IABP a l o n e , mode 11. LVAD a l o n e , mode 111. IABP+LVAD (same t i m i n g ) , mode I V , IABP ( e a r l y diastole)+LVAD(late d i a s t o l e ) , and mode V . LVAD(ear1y d ias to le )+IABP(la te d ia - s t o l e ) . b ined use of both IABP and LVAD (mode 111, I V and V ) than by i n d i v i d u a l d r i v e , b u t t h e r e was no a c t u a r i a l d i f fe rence among t h e s e modes. Cn t h e o t h e r hand, r e n a l blood flow was decreased so dramat ica l ly by the same t iming opt imal counter- p u l s a t i o n method of mode 111, t h a t it was thought t o be harmful f o r r e n a l func t ion . But , t h e de lay d i v i d e combination method o f mode I V and V r e s u l t e d i n no change on t h e r e n a l c i r c u l a t i o n . So, it w a s concluded t h a t , t h i s de lay d i v i d e com- b i n a t i o n mode appeared t o be a more promising suppor t t o both f a i l e d h e a r t and r e n a l c i r c u l a . t i o n . Fu.jio NAGASAKA, Yukihiko CRIME, Yukiyasu SEZAI The 2nd Department of Surgery, Nihon U n i v e r s i t y School of Medicine, Tokyo, Japan

I n t r a a o r t i c ba l loon pumping (IABP) and l e f t

This system ( p u l s a t i l e by-

EVR w a s increased more markedly by com-

239 FORMATION OF 4,4'-METHYLENEDIANILI" I N P O L Y U R E T H A N E P O T T I N G C O M P O U N D B Y G A M M A - R A Y STERILIZATION

We f o u n d t h a t 4 , 4 ' - m e t h y l e n e d i a n i l i n e (MDA) was f o r m e d i n p o l y u r e t h a n e p o t t i n g c o m p o u n d s o f d i a l y s e r s by gamma-ray s t e r i l i z a t i o n .

The a m o u n t o f M D A i n c r e a s e d i n p r o p o r t i o n t o s q u a r e o f i r r a d i a t i o n d o s e . F o r e x a m p l e , t h e l e v e l s i n t h e p a r t i c u l a r d i a l y z e r w e r e c a . 1 u g / g a t 5 Mrad a n d 4 u g / g a t 10 Mrad. T h e l e v e l s i n 8 commer- c i a l l y a v a i l a b l e d i a l y z e r s i r r a d i a t e d a t 2 . 5 Mrad w e r e d e t e r m i n e d .

L e a c h i n g o f MDA t o s e r u m f r o m p o t t i n g compound w a s e x a m i n e d . The l e a c h i n g a m o u n t t o s e r u m w a s a s much a s c a . 65% of t h a t t o m e t h a n o l a t t h e s a m e e x t r a c t i o n p e r i o d . When r e p e a t e d t h e e x t r a c t i o n , t h e t o t a l a m o u n t s o f M D A w e r e a l m o s t i d e n t i c a l i n e i t h e r s o l v e n t .

On t h e o t h e r h a n d , no f o r m a t i o n o f M D A i n t h e r m o p l a s t i c p o l y u r e t h a n e s w e r e f o u n d . The d i f f e r e n c e of MDA f o r m a t i o n b e t w e e n p o t t i n g c o m p o u n d s a n d t h e r m o p l a s t i c PU s h o u l d b e d u e t o t h e a m o u n t o f t e r m i n a l a m i n o g r o u p .

T h e a u t o c l a v e s t e r i l i z a t i o n d i d n o t f o r m M D A i n e i t h e r k i n d o f p o l y u r e t h a n e s .

A k i t a d a N a k a m u r a , H i d e h a r u S h i n t a n i N a t i o n a l I n s t i t u t e o f H y g i e n i c S c i e n c e s , D i v . o f M e d i c a l D e v i c e s , 1-18-1, K a m i y o g a , S e t a g a y a , Tokyo 158 J a p a n

ELECTROMICROSCOPIC OBSERVATION OF MICROSTRUCTURE OF HIGH-PERMEABLE DIALYSIS MEMBRANES BY FR (FREEZE REPLICA) METHOD Purpose: A v a r i e t y of high-permeable membranes

with t h e c la im of removing middle- t o high- molecular weight subs tances have been developed r e c e n t l y . I n t h i s s tudy , t h e s u r f a c e and i n t e r n a l m i c r o s t r u c t u r e s of such membranes were observed by PR method f o r comparing t h e d i f f e r - ences between them.

S u b j e c t s and methods: C e l l u l o s e , EVAL, and PMMA membranes were used f o r t h i s s tudy. FRs of t h e s e membranes were prepared i n t h e prev ious ly- r e p o r t e d manner and observed by a t ransmiss ion e lec t romicroscope .

m i c r o s t r u c t u r e a t both t h e s u r f a c e and t h e i n t e r n a l a r e a , but t h e m i c r o s t r u c t u r e was r e l a - t i v e l y loose and n o t so c l e a r . The same r e s u l t s were obta ined with t h e EVAL C and D membranes. A r i g i d boundary l a y e r was recognized on t h e blood s i d e i n n e r s u r f a c e of t h e PMMA BZ membrane b u t n o t i n t h e BK model. The t h r e e t y p e s of membranes showed some d i f f e r e n c e s i n microstruc- t u r e .

i n m i c r o s t r u c t u r e r e s u l t e d from t h e d i f f e r e n c e of t h e i r m a t e r i a l s . The r e s u l t on t h e Bz membrane was a t t r i b u t a b l e t o t h e manufacturing c o n d i t i o n s of t h e hol low f i b e r .

R e s u l t s : The c e l l u l o s e membrane showed a uniform

Conclusion: I t was supposed t h a t t h e d i f f e r e n c e s

HidemuneNAITO*,HajimeNAGASAKA*,TetsuoMIYAZAKI*, Akira KUBOTSU**.HiroyukiAKASU**,YuichiINUKAI**, Sej suke TAKASHIMA** *: A r t i f i c i a l Kidney Department, Konan H o s p i t a l **: Kuraray Co,,Ltd.

240 ELKTRO-l4E€EiWIcWY DRIVEN, cowuTw CONTROLLED DRIVB SYSTEM FOR INTRA-AORTIC BALLOON

To o p e r a t e i n t r a - a o r t i c ba l loons ( I A B s ) more e f f i c i e n t l y , an e l e c t r o - m e c h a n i c a l l y d r i v e n , computer c o n t r o l l e d d r i v e system has been newly designed. IABs a r e dr iven i n a closed-loop helium (He) gas c i r c u i t . The H e g a s is p r e s s u r i z e d and decompressed by a pusher-plate- type gas pump. The pump is a c t u a t e d by a b a l l screw which c o n v e r t s t h e r o t a r y motion of a b r u s h l e s s d c motor i n t o t h e l i n e a r a x i a l movement . The minimum a n d maximum o p e r a t a b l e ba l loon volumes a r e 2 m l and 40 m l , r e s p e c t i v e l y . An 8 - b i t micro-processor based system is used t o c o n t r o l t h e IAB pumping. The d r i v e modes a r e : 1) ECG s y n c h r o n o u s , 2 ) a o r t i c p r e s s u r e synchronous and 3 ) asynchronous. The s y s t e m h a s an a d d i t i o n a l f u n c t i o n f o r t h e pneumatic d r i v e of t h e l e f t v e n t r i c u l a r a s s i s t d e v i c e ( L V A D ) h a v i n g 60 m l s t r o k e volume. The s i z e and weight of t h e system a r e around 550 x 450 x 350 mm and 30 kg, r e s p e c t i v e l y , i n c l u d i n g a b a t t e r y pack for 1 h backup a p e r a t i o n .

I n v i t r o performance t e s t showed t h a t t h e designed system can d r i v e I A B s a t t h e r a t e of 200 bpm a g a i n s t t h e a f t e r l o a d up t o 180 mmHg. The d i a s t o l i c augmentat ion i n a o r t i c p r e s s u r e and t h e i n c r e a s e i n a o r t i c f low were obta ined . The d r i v e p r e s s u r e must be h i g h e r t h a n t h e a f t e r l o a d p l u s 40 mHg. The d r i v e vacuum w a s n o t necessary .

A s an LVAD d r i v e r , t h e out f low of 5 l/min was o b t a i n e d i n v i t r o a t t h e r a t e of 100 bpm a g a i n s t t h e a f t e r l o a d of 100 mHg.

Takao NAKAMURA, Kozaburo HAYASHI, Masakatsu ASADA*, K e i s u k e SAKAI*, T a t s u z o TANABE*. Res. I n s t . o f A p p l . E l e c t r i c i t y a n d * S c h o o l o f Medicine, Hokkaido Univ., Sapporo, JAPAN

Arfificial Organs. Vol. 13, No. 4, 1989

ABSTRACTS OF THE

241 DILATATION OF STENOTIC REGION IN BLOOD ACCESS VESSEL WITHOUT SURGICAL INTERVENTION AT PATIENT'S BEDSIDE

The conventional treatment of choice for vascular stenosis of the blood acsess has been surgical removal of the region. In order to dilate the stenotic region without surgical intervention within a short time at the patient's bedside. we inserted a micro PTA artery dilating catheter and made a special flow metod in 34 patients. First, we identified the location of the stenosis using DSA of the blood acsess and marked it on the skin.Then.we inserted the PTA catheter through the guiding catheterinto the vessel from a point 4 to 7 cn downstream( or upstream ) of the stenotic region.

The PTA catheter was fixed where the tip was just beyond the stenotic region. The dilatation was made by inflating the ballon at 3 t o 8 at5 for 1 min some 4 to 8 times and the heparinized physiological saline

was injected at rate 10 ml/min through the slit between the PTA catheter and the guiding catheter to keep the flow of the vessels. When the procedure w a s uneffectable.two catheter was fixed near the upstrem and downstream of the stenotic region and then the hep arinized physiological saline was injected at 8 to 13 atm through the slit. Following removal of the PTA catheter.we could make the henodialysis treatment at once .294 & 32 ml/min of the extacorporeal blood flow rate could be obtained after the procedure against the level of 140 2 24 ml/min before it. According to the angiographic findings. the vascular diameter was expanded to 194 5 47 X immediately after the dilative procedure in relation to the value before the procedure. At 3 months,the vascular diameter was still 181 5 41 X over the value before the procedure.

K.Nakane , K.Maeda Nagoya Univercity Branch Hospital, Nagoya, JAPAN

243 CLINICAL APPLICATION OF INTRAARTERIAL AXIAL-FLOW BLOOD PUMP

A new 7-mm i n t r a a r t e r i a l a x i a l - f l o w blood pump can minimize the extensive surg ica l procedures and complications associated w i t h implantat ion o f v e n t r i c u l a r ass i s t devices. The pump i s mounted on a f l e x i b l e i n l e t cannula and pos i t ioned across the a o r t i c valve w i t h i n the l e f t ven t r i c l e . An ex terna l console provides power percutaneously v i a a f l e x i b l e d r i v e cable. Since A p r i l 1988, we have used t h i s pump i n 11 pa t ien ts (mean age, 52 years) i n profound LV f a i l u r e (LVF). Ind ica t ions were postcardiotomy shock ( 7 p t s ) , acute myocardial i n f a r c t i o n ( l ) , cardiac a l l o g r a f t re jec t i on (2), and a l l o g r a f t f a i l u r e (1 ) . The pump was inser ted v i a the femoral approach under f luoroscopic guidance i n 7 pa t i en ts , the ascending aorta i n 3, and the abdominal ao r ta i n 1. During the f i r s t 12 hours o f support, mean cardiac index (CI) was 2.13 f 0.4 L/min/m2 and mean a o r t i c pressure (mAoP), 68 f 9 mHg. I n 10 pa t ien ts , hear t func t ion recovered, a l low ing successful pump removal. The mean CI a t pump removal was 2.98 f 0.3 L/min/m' and mAoP, 69 f 9 mmHg. Dura t ion o f support ranged f r o m 26 hours t o 6 days (mean, 70 hours). No device- r e l a t e d i n fec t i ons o r thromboembolic episodes occurred. P1 asma f r e e hemoglobin remained w i t h i n acceptable l e v e l s du r ing pumping durat ion. I n i t i a l data suggest t h a t t h i s pump can support pa t ien ts w i t h LYF e f f e c t i v e l y and safely. The less complicated surg ica l procedure allows f o r s w i f t i n s e r t i o n and reduces the r i s k o f complications.

Takeshi Nakatani, 0. H. Frazier, Steven M. Parnis, John M. Fuqua, J. Michael Duncan. Texas Heart I n s t i t u t e , Houston, Texas, USA


242

2.44

AMYLOIDOGENECITY I N UREMIA

In o rde r t o c l a r i f y the pathogenetic e f f e c t s of uremic condi t ions on beta-2-microglobulin amyloidosis(BZMA), we s tudied amyloidogenecity of uremic serum, using synovial cu l tu re method and a l s o examined synovial t i s sue(ST) of uremic pa- t i e n t s who underwent wi th in 3 months of d i a l y s i s therapy. H u m a n synovial ce l l s (SC) , p recul tured by conventional method f o r a few days, and ad jus t - ed t o lx104/ml, w e r e cu l tured with following mediums; serum f r e e medium(SF), mediums with normal serum(NS), uremic serum(CF5') o r d i f f e r e n t f rac- t i o n s (Fr) of uremic u l t r a f i l t r a t e s . SC p r o l i f e r a - t i on , B2M production and interleukin-l(1L-1) ac- t i v i t y w e r e measured a t 3rd cu l tu re day. t i o n of B2M t o type 1 collagen was observed i n the cu l tu re with SF, NS and CW.

SC p r o l i f e r a t i o n and B2M production were s i g - n i f i c a n t l y higher i n cu l tu re with CRF than those i n N S and SF(pcO.01). Fr , conta in ing low molec- u l a r weight p ro te ins , showed s t ronges t p r o l i f e r - a t ion and B2M production compared t o the o the r Frs . High I L - 1 a c t i v i t y was de tec ted i n the cul- t u r e with CRF. B2M c leary depos i ted t o type l collagen g e l i n CRF cu l tu re . In ST obtained from autopsy specimens of uremic p a t i e n t s within 3 men- t h s of d i a l y s i s per iod , t yp ica l BZMA was recognized.

These r e s u l t s show uremia i t s e l f play; a responsible role f o r t h e development of B Z ~ .

Deposi-

Yutaka Nakashima, Tadao Akizawa, Shozo Koshikawa I n t e r n a l Medicine, Showa University Fujigaoka Hospi ta l , Yokohama Japan

TREATMENT OF HEPATIC FAILURE BY PLASMA COMPONENT EXCHANGE

The purpose of plasma exchange in hepatic failure is to remove accumulated toxic substances resulting from impaired hepatic detoxication, and to supplement coagulation factors which are decreased by impaired hepatic biosynthesis to sustain patients until recovery ensues.

To achieve this efficiently and economically, we have developed plasma component exchange, which is capable of removing selectively low-molecular substances less than 100,000 dakons form blood while retaining necessary high-molecular proteins, using membrane type plasma component separator, EVAL-3A (Kuraray Co., Ltd.) and 2.4 - 4.8 litters of diluted fresh frozen plasma.

The new therapy was conducted a total 45 times in 8 patients with hepatic failure. Five of our 8 patients recovered.

With only half as much fresh frozen plasma, plasma component exchange can provide the same ability to remove toxic substances and supplement coagulation factors as dose conventional plasma exchange using membrane type plasma separator. Takuro Nakayama, Hisashi Yasuoka, Takao %no, Tastushi Kishino Department of Internal Medicine, Kochi Nokyo General Hospital, Nangoku, Japan



245 HEMODIALYSIS SCHEDULE ACCORDING TO SCHOOL RHYTHM AND GROWTH I N TEENAGERS

In order t o comply with the rhythm of school attendance and t o improve d i a l y s i s tolerance, s i x teenagers (14-19 yea r s o ld ) were switched from a 4 . 5-hr double-needle (QB: 250 mllmin), three t i m e s a week t o a 2. 25-hr single- need le (QB: 150 ml/min), f i v e t imes a week d i a l y s i s st r a t egy .

Dia lys i s sessions w e r e performed a f t e r school hours. Dialysate composition (bicarbonate) , d i a lysa t e flow r a t e (500 m l / m i n ) , nature of membrane (polysulfone) and type of d i a l y z e r (F 40 Fresenius) were unchanged.

After 1 6 mnths fo r 3 pat ients and 6 mnths f o r 3 other pat ients , t h e biologic p ro f i l e of t he patients on t h i s new d i a l y s i s s t r a t e g y compared t o t h e s t anda rd d i a l y a i s s t r a t e g y showed no s i g n i f i c a n t change, except a 5 % dec rease i n p r e d i a l y s i s plasma c r e a t i n i n e and a 50% decrease i n heparine admin i s t r a t ion .

It is noteworthy t h a t a l l the pat ients gain a lean b d y mass of 2 Kg and i n three pat ients (0. C., T. D. and A.C.) t h e slope of t h e growth curve (Height i n cm/Time i n m s ) has changed from 0.37, 0.30 and 0.17 t o 0.69, 0.57 and 0.25 r e spec t ive ly .

In s p i t e of i n c r e a s e d d i a l y s i s f requency and a u l t r a f i l t r a t i o n r a t e of 1 L/h for a mean (f SEM) body weight of 31.5 f 2.7 Kg, c l in i ca l tolerance was excellent, probably due t o t h e absence of washout syndrome, gain i n sleeping time and small changes i n body weight and so lu t e concentrat ion.

Most important ly f o r t eenage r s p a t i e n t s , t h i s new d ia lys i s s t ra tegy prevents school absenteisrn which r e su l t s i n normal school a t tendance.

C., P . Garnier , P. Chauveau, C. Ciancioni , s. Delons, N.K. Man E. R i s t Medical Center, Hormonology Research Foundation and Necker Hospi ta l , P a r i s , France.

247 TRANSESOPHAGEAL ECHOCARDIOGRAPHIC FINDINGS OF INTRACARDIAC EVENTS DURING CARDIAC ASSIST

Transesophageal echocardiography (TEE) is an easy and reproducible t o o l for evaluation of left ventricular function, coronary flow pattern and intracardiac blood flow. In three cases of ventricular septa1 rupture following acute myocardial infarction, left ventricular assist devices (LVAD) were used after the surgery and one long term servivors was obtained. During cardiac assist, TEE gave u s the various informa- tions as follows; 1) The catheter tip position in the left atrium is a critical point for getting a good LVAD flow. Observing the catheter tip by TEE, it could be settled just above the mitral orifice. 2) The intracardiac thrombus could be clearly detected by TEE at the drawing catheter inserted site. It was removed without any complications, weaning from LVAD. 3) The left ventricular wall motion was period- ically observed. The endsystolic LV diameter (LVDS) was decreasing and contrarily fractional shortening ( X FS) was increasing gradually. Additionally the pre-ejection period (PDP) and the ejection time (ET) were measured. The ratio of PEP/ET was decreasing gradually. LVDs seems to be a more reliable parameter for cardiac recovery than others under LVAD pumping. 4 ) The flow velocity in the left main coronary trunk could be measured by doppler TEE. It was clinically shown that counterpulsation produced higher coronary flow than copulsation. Michihiro Nasu, Yukikatsu Okada, Hiroshi Fujiwara, J u n Sono, Sunao Nishiuchi, Kiyoshi Tatemichi, Toyo Shomura Department of Thoracic Surgery, Kobe City General HosDital. Hvoeo. Jauan

246 LATISSIMUS D O R S I CARDIOMYOPLASTY: EXPERIMENTAL STUDY

Hemodynamics under b i v e n t r i c u l a r suppor t w i t h l a t i s s i m u s d o r s i muscle (LDM) ca rd iomyop las ty were i n v e s t i g a t e d i n 6 dogs. Both v e n t r i c l e s were wrapped around b y t h e d i s s e c t e d l e f t LDM which was e l e c t r i c a l l y p r e c o n d i t i o n e d f o r more than 6 weeks. descending a o r t a (AOP) and t h e main pulmonary a r t e r y (PAP), LDM was s t i m u l a t e d synch ronous ly w i t h a s p e c i a l l y des igned b u r s t s t i m u l a t o r . Synchronous s t i m u l a t i o n of t h e LDM inc reased s y s t o l i c AOP and PAP, demons t ra t i ng s y s t o l i c augmentat ion of b o t h v e n t r i c l e s . However, s t i m u l a t i o n w i t h h i g h e r r a t e s above 120 bpm r e s u l t e d i n t h e decrease of AOP, w h i l e t h e decrease o f PAP d i d n o t occu r up t o t h e r a t e of 150 bpm. S y s t o l i c augmentat ion o f ADP was most c l e a r l y demonstrated when t h e s y s t o l i c AOP was 50-100 mmHg, w h i l e synchronous s t i m u l a t i o n d i d n o t i n c r e a s e t h e s y s t o l i c p ressu re w i t h l ower AOP under 50 mmHg. e a s i l y augmented b y t h e LDM c o n t r a c t i o n under any c o n d i t i o n w i t h l ower h e a r t r a t e s .

The r e s u l t of t h i s exper iment shows t h a t w i t h t h e LDM ca rd iomyop las ty wrapped around b o t h v e n t r i c l e s , t h e c i r c u l a t o r y suppor t o f t h e r i g h t h e a r t i s more e a s i l y achieved than t h a t o f t h e l e f t h e a r t .

Wh i le m o n i t o r i n g p ressu res o f t h e

S y s t o l i c p ressu re o f PAP was

Y. Naruse, T. Takahana, H. Okabe, H. Makuuchi, H. Matsunaga, A. Furuse Dept . o f T h o r a c i c Surgery, Univ . o f Tokyo, Tokyo, JaDan

248 S O W T I O N PURIFICATION OF TRANSFUSION mDIA

Per fus ion #of s t o r e d blood and packed r e d c e l l s through t h e sorbent SKN-D results in improvement of oxygen t r a n s p o r t e r y t h r o c y t e funo t iona1 ,a 38% i n c r e a s e of ATP Icontent and a 10-fold decrease of spherocyte amomt . Concentration o f c i t - r a t e , l a c t a t e and middle molecular subs- tanoe(MMS)deoreases 71%,5O% and 75%,re- s p e c t i v e l y . Noimal i z a t i on of ac id-base and e l e c t r o l y t e status of blood and i t s r l i eo log ica l p r o p e r t i e s a r e (observed; de- f I o r m a b i l i t y and e lec t rophore t i c mob i l i t y of e r y t h r o c y t e s i n c r e a s e 30% and 5056,respectively.When adenine and inos ine are p r e s e n t i n the p r e s e r v a t i v e t h e i r con- t e n t decreases 5-7 t imes.

m a through (carbon so rben t s enables the Icon t en t of c i t ra t e , hMS and f ib r inogen degrada t ion produlcts t o be reduced 2-5 t imes.

min hioreases the a s s o c i a t i o n oons tan t for b i l i r u b i n and methyl r e d 2,5-5 t i - m e s and t h e number (of b inding s i t e s 1.5- 2 times with 613-8056 inc rease (of tcorgo r e d amount brdund p e r weight unit of an albumin.

T h u s t h e s a r p t i o n p w i f i o a t i o n of t r a n s f u s i o n media r e s u l t s i n an impmve- ment of t h e i r funr: t i o n a l c h a r a c t e r i s t i c s . V.G .Nikolaev, A.L. Belkin,Id.P .Metal ‘nikova I n s t . f o r Oticolcgy Prijblems ,Ai:ad.Sci. of ‘chi= T:kr.SSE,Kiev,USSR

Fer ths ion iof f resh- f rozen donor p l a s -

So rb t ion p u r i f i c a t i o n of serum a lbu-



249 THEFJWDYTJAMIC APPROACH TO THE EVALUATION 250 STUDY OF LASER WELDING I N OF A PLASMA LFJEL OF PROTETIGBOUND WASTE CARDIOVASCULAR SURGERY MEYTP BOLTTES D i f fereri t ial soanning calorimetry (DSC ) [&La have demonstrated that sodium capry- 1af.e added to a human albumin (HSA) solu- tic)n at 0,1-?0 mole/mole ratios leads to a monotonous growth of melting temperature (MT) iuf albumin from 61 to 82OC. When HSA is loaded with bilirubin at 0 , O l - 3 rnoleimole ratios, oiomplex conformation rearrangements (of pmtein molecules are observed with MT (change to 76-78OC. M I (of a1 tiumin separated by hollow-fiber filter f r o m the blocd plasma of healthy donors and patients with hepatic insufficiency was 62-63 and 77-7g°C, respectively, with the shift (of the latter by 2-4'C due to an extensive plasma sorption. MT of albumin separated from the blood of uremic patients is 73-80°C,with MT remaining un- ohanged after intensive plasma ultraf il- tration.Albumin MT measu-ements in native plasma gave similar results. Microcalori- mstric, titration and equilibrium dialysis data point to a close relationship between albumin MT, enthalpy, entropy and its transport capacity. The authors suggest that the thermodynamic characteristics of albumin melting can become a new (criterion of non specific evaluation the severity of endogenous intoxication and the efficiency of removal of protein- bound ligands from blood. V.G.Nikolaev, P.V.Osadchy, V.V.Sarnat- skaya, 7 . L. Ponomarev, Ya.P .Kovalishin, A.V.Verbinenko T h e Institute for Oncology Problems, Acad.of Sci.Ul;r.SSR, Kiev, USSR.

25 1 COHPARATIVE STUDY OF RIGHT HEART ASSIST WITH PUSATILE OR NON-PULSATILE FLOW

T h i s s t u d y WAS t o e v a l u a t e hemodynamic e f f e c t on and d i f f e r e n c e between RVAD as a p u l s a t i l e a s s i s t and c e n t r i f u g a l pump(CP) as a n o n - p u l s a t i l e assist f o r a c u t e RV f a i l u r e . Under g e n e r a l a n e s t h e s i a , 8 a d u l t dogs were ins t rumented through mid-sternotomy. P r e s s u r e c a t h e t e r s w e r e i n s e r t e d i n t o FtA,RV,PA,LA,LV and aorta, and a l s o a o r t i c and coronary s i n u s f lows were measured. We l i g a t e d i tV f r e e w a l l and d i a pulmonary a r t e r y banding(PAB).

E i t h e r RVAD o r CP.ags is t w a s d r i v e d a t f low r a t e of 20%,40%,60%,80% of t h e a o r t i c f low a t c o n t r o l . Both RVAD and CP s u p p o r t s could improve hemodynamics a t any f l o w r a t e , b u t s i g n i f i c a n t l y improve a t f low rate of more than 4 0 % , a l t h o u g h e x c e s s i v e i n c r e a s e of PA p r e s s u r e w a s recognized . There w a s no s i g n i f i c a n t d i f f e r e n c e o f hemodynamics between t h e two systems, and both RVAD and CP e f f e c t i v e l y s u p p o r t t h e RV dur ing a c u t e RV f a i l u r e w i t h PH.

; u n i c h i Ninomiya,Shigeo Tanaka, Shigeo Yamauchi, C e i k i Morioka, Naotoshi Sa igusa , s i n i c h i Osaka, l a s u k u S h o j i , Yukihiko Nose, Takeshi Aizawa 1wpt .Thorac ic Surgery , Nippon Medical School Tokyo, Japan

T h i s s t u d y i s t o e v a l u a t e t h e p o s s i b i l l i t y and t h e e f f i c a c y of laser v a s c u l a r weld ing e x p e r i - m e n t a l l y and c l i n i c a l l y . W e anastomosed 2 1 c a n i n e p e r i p h e r a l and coronary arteries w i t h o r wi thout b i o l o g i c a l v a s c u l a r g r a f t by Nd-YAG l a s e r w i t h c o n t a c t method.

Vascular welding w i t h o u t b i o l o g i c a l g r a f t s u c c e s s e d i n a l l c a s e s , and t h i s pa tency r a t e was 100% i n p e r i p h e r a l a r t e r y and 83% i n coronary a r t e r y . The welding f o r b i o l o g i c a l g r a f t t o p e r i - p h e r a l and coronary a r t e r i e s a l s o successed i n 92% and 83% of a l l c a s e s r e s p e c t i v e l y . The e a r l y pa tency r a t e was b o t h 100%.

f o r h i g h p r e s s u r e and f u s e d w e l l w i t h o u t s i g n i f i - c a n t damege of i n t e r n a l l a y e r which w a s proved by t h e p o s t o p e r a t i v e h i s t o l o g i c a l f i n d i n g s .

I n c l i n i c a l s t u d y w e anastomosed t h i s g r a f t t o 9 human r a d i c a l o r femora l a r te r ies by t h e same l a s e r and t h e pa tency ra te was 100% w i t h o u t any compl ica t ions .

I n conclus ion , Nd-YAG l a s e r w i t h c o n t a c t method could s u c c e s s f u l l y weld p e r i p h e r a l and coronary ar ter ies w i t h o r w i t h o u t i n t e r p o s e d b i o l o g i c a l g r a f t .

These anas tomot ic s i t e s w e r e s t r o n g enough

J u n i c h i Ninomiya, Shigeo Tanaka, Tasuku S h o j i , Koichi Tamura, Yasuharu N o i s h i k i Dept. Thorac ic Surgery , Nippon Medical School Tokyo, Japan

252 VASCULAR RESPONSIVENESS TO VARIOUS VASOACTIVE SUBSTANCES AFTER EXCHANGE TRANSFUSION(ET) WITH PYRIDOXYLATED HEMOGLOBIN-POLYOXYETHYLENE CONJUGATE (PHP) SOLUTION I N ANESTHETIZED RATS.

Vascular respons iveness t o v a r i o u s v a s o a c t i v e s u b s t a n c e s a f t e r ET wi th PHP was examined i n a n e s t h e t i z e d rats. The h indl imb-region was per- f u s e d w i t h blood v i a cannula i n s e r t e d i n t o t h e a o r t a w i t h a pump a t c o n s t a n t f low rate . Acety l - chol ine(ACh), Ni t roglycer in(NG), Nornephrine (NE), Angio tens in II(A-111, and serotonin(5-HT) were emplyed f o r examinat ion of v a s c u l a r respon- s i v e n e s s i n t h e hindl imb-region. Drugs were i n j e c t e d i n t r a a r t e r i a l l y and changes i n p e r f u s i o n pressure(PP) and sys temic a r t e r i a l p r e s s u r e (SBP) were measured. I n t h e c o n t r o l c o n d i t i o n , ACh and NG induced a d e c r e a s e i n PP, w h i l e o t h e r d r u g s i n - c r e a s e d PP. A f t e r ET w i t h PHP s o l u t i o n , v a s c u l a r r e s p o n s e s t o each drug were t e s t e d .

The response p a t t e r n of changes i n PP by each drug w a s n o t a l t e r e d , b u t t h e magunitude of each response was augemented. The augementat ion of t h e response t o each drug a l s o occured a f t e r ET w i t h 6% hydroxyethyls tarch(HES) s o l u t i o n . R e s u l t s s u g g e s t t h a t t h e augementat ion of t h e response may be due t o changes i n hemodynamic p r o p e r t i e s of c i r c u l a t i n g blood a f t e r ET, b u t n o t t o PHP-moiety p e r se, and hence, v a s c u l a r r e s p o n s i v e n e s s t o t h e s e drugs i n t h e h indl imb may n o t be a l t e r e d a f t e r ET w i t h PHP s o l u t i o n ,

KacWhide N i s h i , Y o s h i t o s h i Kida, Seinosuke Iwata , Yuichi Gyoutoku. Department of Pharmacology, Kumamoto U n i v e r s i t y Medical School , Kumamoto, Japan and L i f e Sc ience L a b o r a t o r i e s , C e n t r a l L a b o r a t o r i e s , Ajinomoto Co. , I n c . , Yokohama, Japan

--



253 Oxygen radical release from neutrophi I s related to biocompatibilits of dialysis membrane.

Hemodi alys is ( HD 1 1 eukopeni a re1 at etl to complement(C) ac1.ivation is well known. However, oxygen radical production from a polymorphonuclear leukocyte(PMN1 which is stimulated by dialysis membrane is still unknown. I n the present study, the ability of different dialysis membrane to activate PMN is invest.igated. PMNs were collected during HD and oxygen radical release was detected by P a t e l ' 3 method. The 2'7'-dichlorofluorescin was oxydized by hydroxyradical t.o yield the highly fluorescent. product dichloro- fluorescein. The f1uoresc:ein positive cells are analysed by flow cytometer. The % of c e l l s stimulated by phorbor- miristate acetate or opsonized zymosan was detected. The com~lementsiC3a and C5a) and 1 i pid peroxidationf ma Ioridi - aldehyde) were also determined. At 5-15 min. of dialysis time, a highly amount of radical product was observed by PolymethYlmethacrylate membrane. The amount of oxygen radicals varied with the membrene materials. These data suggest that the oxygen radical production during HD may become one of likely mediator of biocompatibiblity cf HD membranes.

AishikawaM_, Sanaka T, Satou T, Hisuchi T, Omata M, Nihei H, Agishi T, Ota K and Sugino N. Kidney Center, Tokyo Women's Medical College, Tokyo, Japan

255 DEVELOPMENT AND EVALUATION OF CLINICAL VENTRICULAR ASSIST DEVICE (VAD) SYSTEM INCLUDING AN AUTOMATIC CONTROL SYSTEM

We have been engaged in the development and evaluation of clinical ventricular assist device including micro sensors and optimal automatic drive system. Our sac-type air driven VAD was composed of sac, inflow and outflow cannulae and valve- built-in connector which connects sac and cannula. So we can always develop, improve and exchange any parts independently once some disadvantageous episode happens. Recently, we have been evaluating silatic ball valve for VAD in the chronic animal experiments for 2-3 month and in the mock circulation for over 6 month showing any thrombus formation and any breakage of entire VAD. As an automatic control system, a new hemodynamic measurement system has been developed using micro pressure sensors on the wall of both inflow and outflow cannulae to have an adaptive controller of VAD system. With this automatic control system, we newly designed the wean-off method without any volume administration and any cease of VAD drive by changing the drive phase from diastole to systole automatically which resulted in increase of LV outflow impedance. This new method was evaluated in the 7 animal experiments to obtain a LV pressure-volume loop by pressure sensor and condanctance catheter in the LV cavity which revealed the usefulness to estimate the recovery of cardiac function during LVAD pumping. Shin-ichi Nitta,Y.Katahira,T.Yambe,T.Sonobe, H.Hayashi4M.Miura:N.Satoh:H.Mohr?, M.Yoshizawa* & H.Takeda?Dept.of Med.Eng.& Card. ,Res.Ins.for Chest Dis.& Cancer, *Dept.of Thorac.Surg., Sch.of Med. ,*Faculty of Eng., Tohoku University

254

256

EXPERIMENTAL STUDY OF PUMPLESS ECMO DURING 24 HOURS USING EXTRACAPILLALY BLOOD FLOW TYPE POLYPROPYLEN MEMBRANE OXYGENATOR

To remove carbon dioxide in acute respiratory failure, pumplessECM0 experiments were carried out using extracapillaly blood flow type membrane oxygenator, which was developed by our department and which has many advantages; compact, small priming volume and low pressure drop. The oxygenator is consisted with 17cm in length, 200um in innerdia- meter, made of polypropylen with micropores. And it has 0.7$of surface area and about 6Oml of priming volume. In 14canines acute respiratory failure were made by hypoventilation(T.V.=lOml/ Kg, R.R.=5times/min). We cornpaired with hypoventilation group(group 1, n=5)and pumplessECM0 group(group 2, n=9). PumplessECMO circuit is A-v bypass between femoral artery and vein. The following results were obtained.

were observed, and all 5canines were died within 4 hours.

2)In group 2 hypoxia and hypercapnea were improved by pumplessECM0, 4 in 9 lived for 24 hours.

3)Function in COztransfer with the P.H.0.is maintained in satisfactory conditions for 24hours.

4)The oxygenator seems to be available for relative long-term pumplessECM0.

5)Degeneration of mitochondria in the acute respiratory failure was observed by electron microscopic examination.

6)Further examinations about the intracellular respiration and metabolism in pumplessECM0 should be needed. Osamu Nishimura, Kazumitsu Ohmori, YOshiyuki Ishii, Hiroshi Natori, Mamoru Horikoshi, Yukiyasu Sezai The 2nd Department of Surgery, Nihon University Shoo1 of Medicine, Tokyo, Japan.

llIn group 1 severe hypoxia and hypercaprea

APPLICATION OF ULTFiAFINE POLYESTER FIBERS (WPF) TO HIGHLY POROUS VASCULAR SUBSTITUTE

We developed two kinds of highly porous vascular substitutes(HVS) made of UFPF and evaluated their applicability in animal experiments. LEXP.1: small caliber model] An autologous connective tissue tube(3mm ID)

was made using HVS as a basic matrix, and was implanted into the carotid arteries of dogs. [EXF.2: large caliber model] Autoblood-preclotted HVS(8mm ID) were

implanted into the thoracic descending aorta of dogs.

Numerous fibroblasts and capillaries were observed in the wall of both vascular models by light microscopy. Scanning electron microscopy revealed openings of capillaries and endothelial cells on the middle portion of the graft as well as at the anastomotic sites even in the early stage after implantation.

These results suggest that UFPF provide a suitable micromatrix for the infiltration of fibroblasts accompanied with the angiogenesis of the graft wall, and resulting capillary opening promotes endothelial cell proliferation on the inner surface of the graft.

Thus, UFPF appears to be a useful for vascular substitute promoting endothelialization.

S.Niu, S.Satoh, S.Shirakata, T.Oka, Y.Noishiki, H.Kurumatani, K.Watanabe Department of Surgery 11, Kyoto Prefectural University of Medicine, Kyoto, Japan



257 METHODS FOR REPIOVAL OF PROTEIN-BOUND METABOLITES ACCUMULATED IN UREMIC SERUM

Since protein-bound metabolites such as indoxyl sulfate (IS) and 3-carboxy-4-methyl-5-propyl-2- furanpropionic acid {CMPF), accumulated in uremic serum as inhibitors of drug-binding could not be rmoved from blood by conventional hemodialysis, we studied on the methods for removal of these protein-bound metabolites.

First, plasma exchange can remove these protein bound metabolites. However, plasm exchange is a lJborious work, and cannot be carried out periodi- cally for dialysis patients.

Second, 09PD could remove these protein-bound metabolites more efficiently as compared with conventional hemodialysis, since serum levels of IS and CT.IPF in W D patients, 20.0+11.4 pg/d and 13.8i7.9 ug/ml, respectively, were fairly lower than those (32.6214.8 ,ug/ml for IS, 47.1t15.3 pq/ ml for CMPF) in hernodialysis patients. Normal levels for IS and CMPF were 0.5t0.3 p g / d and 3.6k2.4 ug/ml, respectively. The albumin binding of IS and CMPF in uremic patients were 90% and 99 '6, respectively. BY CAPD 26.5 m9 of 1s and 1 - 3 mg of CMPF were removed daily into dialysate.

Third, IS could be removed efficiently by adsorption on activated charcoal and also on cationic resin. However, W F in uremic serum could not be removed by activated charcoal nor by cationic resin. Hemadsorption with activated charcoal is an efficient method for removal of protein-bound IS in uremic patients.

120) could decrease serum level of IS. Toshimitsu Niwa, Tomoko Yazawa, Kenji Mae& kpartment of Internal .%&cine, Nagoya University Branch Hospital, Nagoya, Japan

Fourth, oral in'iake of activated charcoal (AST-

259 LIPID LOWERING EPPECT BY THERMOFILTRATION IN WBHL RABBIT

It is still questionable whether or not the prevention of the progression or the regression of established atherosclerosis can be achieved only by serum cholesterol removal. The objective of this study is to evaluate the effect of plasma lipid lowering on the progression of atherosclerosis in homozygous Watanabe heritable hyperlip- idemic rabbit. The effect of lipid lowering, which was accomplished by thermofiltration (on- line plasma separation with plasma filtration at 37°C with the Kuraray Evalflux filter) was evaluated by comparison between the treated and untreated control group. One plasma volume was treated once per week for about 10 weeks. Thermo- filtration reduced the mean total cholesterol (p<O.OOl) and the % occupancy of atherosclerotic plaque in the aorta (pt0.0008) significantly.

Group - No. Cholesterol of Aorta Treated n=5 290 f 46 mg% 15.1 f 8.4 % Control n=6 655 f 173 mg% 44.2 f 10.6 Z

The total lipid content in the aorta in the treated group was also significantly lower than that in control (62.2 vs 101.1 mg/g of tissue). Histologically, thickness measurements of the atherosclerotic lesions showed that the mean amount of fibrous plaque thickening, the thickness of the intima, and the ratio of the intima and media were smaller for the treated group. This study demonstrates the stopping o r slowing of the progression of atherosclerosis by lowering the cholesterol level in WHHL rabbits. Eideaki Nomura, Paul S . Malchesky, Masato Yamashita, Andrzej Werynski, Yukihiko Nos&, Cleveland Clinic Foundation, Cleveland, Ohio, USA

Mean Total Mean % Plaque

258 IN VIVO PROTEIN ADSORPTION ONTO CANINE AORTIC GRAFTS: TEM /SEM VISUALIZATION OF ADSORBED PROTEINS .

This paper demonstrated top0 raphical analysis of - in viva protein adsorption on pofymers using transmission electron microsco y (TEM) and scannin electron microscopy &EM). Vascular graft (6mm If!)), coated n its lumnal surface with test pol mers (Biomer 8 (B), PEO rafted Biomer (B-PEO) anJHEMA-St rene blockcopof mer (H S)), was implanted in agdominal aorta oydogs. At 1 and 3 months after implantation, the grafts were retrieved for TEM/SEM anal sis. Detection of adsorbed proteins (Alb, Fib, fYgG) by TEM involved a double immunostaining using peroxidase conjugated second antibody, and a protein-A-gold technique for SEM. Os04 was also used to measure the protein layer thickness by E M . The results indicated that the protein layer thickness for B and B-PEO increased with time. In contrast, H-S showed the same thickness for up to 3 Mo. TEM demonstrated multilayered rotein adso tion pattern, increasing with time for% and B-PE8, whereas, H-S maintained a monolayer pattern even after 3 Mo. SEM showed dominant coverage of Fib for B and B-PEO, and greater amounts of Alb and IgG with less Fib were observed on H-S surface. These observations correleted with previously reported in vitro platelet adhesion and activation studies and ex vivo A-A shunt occlusion time. The less thrombogenic surface, H-S, showed a monolayer protein adsorption pattern, and less Fib affinity in vivo. These data suggest that the surface property of the polymer can control in vivo protein adsorption, subsequent cellular adhesion and thrombus formation. Chisato Noiiri, Teruo Okano, K. D. Park, Sung W. Kim University of Utah, Salt Lake City, Utah, USA

260 DEVELOPKENT OF A POLYMER VALVE FOR USE IN AN ARTIFICIAL VENTRICLE

A butterfly type valve has been fabricated for use in an artificial ventricle. The valves which are designed to fit into the tubular inflow and outflow tracts of the ventricle bladder, have long tapered flow paths with minimized areas of stasis. A small 30" flex angle induces good washing and extends flex life. The cross sectional area of the leaflet is designed for maximum flexibility while avoiding prolapse. The ventricles bladder, valve seats and leaflets have similar biocompatible carbon containiiig surfaces. provide dimensional control, excellent reproduc- ability and inexpensive fabrication.

500 mm/Bp,. Four sets of valves have been cycled 2.5, 7.0, 7.3 and 8 million times 05 the equivalent of 2 9 , E l , 8 4 and 93 days and cycling contimes. There t ~ a s been one valve failure at 5 million cycles. In vitro hemolysis studies in a Sernstein type loop yields an Index of Hemolysis of .016.

Molded valve leaflets

All valves must withstand static pressure of

Scoi , George F., Feldman, Louis, Sherper, Charles; Gludck, Julia; Fernandez, JuLn: Dcaekey, M.E. ' Baylor College of EIedicine ' Hauston. uxas U.S.A.


348 ABSTRACTS OF THE VIlth WORLD CONGRESS

261 pi VI'IRO \~ISUAI,IZATIUN OF THE. FU% PA'ITERNS OF THE WlR% \ i lRlTX PCPIF' .AM) 4 COMIENTIONAL V E N T R l C L M ASSIST DEVICE The "spiral vurtrs pump" (SO, an innovat ive , pneruiiat i ca I I $-dri veil i e n t . r i c u l a r assist device rcas canImred t o a ;xnir.ent.ional tip? ICTJ i n a p e l irni.nai'> assessment. of its floii c h a r a c t e r - i s t i c s . 'The pumps rTe1-e operated i n a mock c i r c u - l a t o r ? ioq) u s irig wat.er conta in ing p l a s t i c micro- s i ~ h c r e s . The f l o w f i e l d s rere photographed usinq I i i g I ~ - s p e d cine, and t h e records later t r a n s f e r m d tm \ ideo. Ghmlit.ative and q u a n t i t a t i \ - e c imp. r i son of t ijr records demui~sl.rat,rd t h e i n t r i n s i c a l l y ( I i t 'ferwit p r o p r t i r s i,f t h e SV, as envis ioned i n it:. desigii c:~x~ept . In d i a s t o l e a l a r g e , c i r c u l a r f l oc st.rearii, rchich i n i t i a t e d a t t.he t s n g e n t i a l l y - I!,il.areJ i n l e t , s t e a d i l i . involved t h e e n t l r e flow f ie ld i n a cwherent, s p i r a l vor tex , i;ith peak pxrtit:Lc. wlcsii ies (?\-sj of i0 cm/sec recurring near Lhe ( e 1 - j phery. During s y s t o l e , Lhe v o r t e x ~ ~ n i ~ e r . g e d h e l i c a l 13 t o pass Lhrrmgli the a p i c a l l y - 11.catt.J u u t l e t . In cor , t rae t , t h e C T demonstrated !i?ghl> i ri,egiilai. Iloi-, patterns. A Large vorte?. twgarl Io c I c \ t ~ l o p i n e a r l y ;diastole, b u t is:+s imin ly # l i s s o c , i a i e ~ l p r i o r t o t h e o n s e t of s y s t o l e . F l o ~ i ~ - i r : u l a t ioii and c ~ t I i d ing s t r e a m l i n e s t-iccurrtxl I h~~or ig l i~-~ur t Ile iloic f ' ie ld , S O R I ~ particles r e i w i i i , i r g \,i :.tiin th- I U I I I ~ for s e v e r a l r y c l e s . 3~ asi ii.ed 19s K ~ I Y . 1 owti l ' [ redc 4 5 crn/sec) , -ugxes t I rig t ha I i - iscous cf frct s i n t,lie c i i nc?rde~-rrl f Lri.. < v i i\.c:i-ted t.lw 1 I ilet f.loris!.re:am iriumc ill urn i i 11 o :,.II bu1eia:c.. Tlie s i i l ~ r i o i ' f l o r < ,:liarac:l..eirist

263 A VASODILATATOR (CGRP) AND A 264 VOLUMEMARKER (ANP), ACCURATELY DESCRIBE THE PATHOGENESIS OF HYPERTENSION (BP) IN HEMODIALY SISPATIENTS.(HD)

Hypertension is an important cause of morbidity and mortality in dialysispatients. The pathogenesis is a mixture of overhydration and vasoconstriction.There are no good clinical markers for the relative role of each and treatment then is empirical and unsatisfactory.

We tried to elucidate the pathogenesis of hypertension of HD patients by analysing 9 vasoconstrictor hormones: Neuropeptide-Y, Norepinehrine, Epinephrine, Dopamine, Renin, Angiotension-11, Aldosteron, Cortisol and Vasopressin. Two Vasodilatory hormones Calcitonin Gene Related Peptide (CGRP) and Neuropeptide -K (NPK) and one volume-marker Atrial Natriuretic Peptide (ANP)., and relate them to BP. We used linear, multiple and stepwise regression analyses to study correlations.

In single regression analysis, using BP as the dependent variable,R was < 0.5 and p > 0.1 for all hormones but CGRP (R=0.79 and ~ ~ 0 . 0 2 ) and NPY (R=0.6 and p<

Best fit was obtained by multiple regression analysis , using predialysis syst BP as dependent variable of CGRP and ANP. (R=0.9, p<O.Ol).

Our preliminary observations indicate that a combination of CGRP and ANP determinations, accurately seem to describe over 80% of the pathogenesis of hypertension in HD patients and give very important clues to the correct treatment, with ultrafiltration, vasodilarory BP medications.or both

o.os)

I.Odar-Cederlof. E.Theodorsson, P.Thylen, CG Eriksson, F.Eriksson, B.Hamberger, B.Tidgren. C.Kjellstrand.Depts of Medicine, Clin. Chemistry, Clin Physiology and Surgery Karolinska Hosp and Inst, Stockholm, Sweden.

262 TRAIAL OF ANTICANCER JMlUNO-THERAPY BY HEMOPERRT- SION WITH POKEWEED MITOGEN PlrIOBILIZED BEADS

Pokeweed Mitogen(PWM), a sort of l e d i n , have a potential t o induce anticancer c e l l . In order t o u t i l i z e this potent ia l and t o apply for cancer therapy by hanoperfusion with this material, w e imnobilized PWMto M - D V B bead. In v i t r o assay: Humin peripheral lymphocytes were separated by lymphoprep, and lymphocyte suspension was circula ted through t h e PWM-C for 2 hours. The flow r a t e was O . g m l / m i n . A f t e r circulatory contact stimula- t i o n with PWM-C,lymphocytes were collected and used f o r effector cells. Cytotoxicity tests were measured by C r release assay using K-562 cell and Daudi cell for target cell. T h i s material could argument t h e NK ac t iv i ty and L4K like act ivi ty . In vivo t r i a l : WKA rat under pentobarbital anesthesia,direct henmperfusion(DHP) was performed for 60 minutes using a column containig 3ml of PWM inmobilized beads(PWM-C).The flow r a t e was O.gml/ min. All DHP could be performed safety without hanocoagulation. The blood pressure dropped s l igh t ly during DHP. There w e r e no s ignif icant changes examinati0ns.h vivo anticancer effect:Anticancer a c t i v i t i e s were examined in Vx2 rabbi ts by the treatment of DHP with PWM-C. Tumor bearing rabbi ts were obtained by t h e intrrurmscular injection of Vx2 tumor cells a t la106 viable cells in to t h e i r thigh. Single DHP treatment using PWM-C w a s performed 5th day a f t e r tumor inoculation. The suppression of t h e t m r growth could be found for 25 days. PWM-C can be expected for anticancer material as an innnunomodulator. K e n j i Numa, Tani Tohru, Hajime h e , Toyokazu Yosioka, Yosihiro Endo, Masasi Kodama 1st. Depertment of Surgery , Shiga University of Medical Sciense, Ohtsu, %ga, Japan

in blood gas analysis and hematological

t w r bearing

B2MICROGLOUBULIN ( B m ) KINETICS IN END-STAGE RENAL DISEASE (ESRD)

In evaluating the effectiveness of extracorporeal removal of B2M, it is necessary to consider the metabobic clearance as well. This study examines the metabolic and dialytic clearance of B2M

Human B2M was isolated from peritoneal dialysate using ion-exchange and gel chromatography and radiolabelled Purity of B2M was determined with gel electro heresis. Four anephric ESRD patients received i.v. lOpCi P251-B2M. Plasma 12%-B M profiles were determined over 72 hr. Later, lOpCi &I-Bfl was given to four anephric ESRD patients 24 hours before a conventional low flux (") dialysis. High flux dialysis (HF,Bellco BL655) was performed the next day. Results are expressed as mean sd

A 3 pool model was used to determine the metabolic clearance of B2M. The 72 hr turnover study gave a plasma B2M clearance of 3.3 & 0.5 ml/min (n4). Dialyser clearances of endogenous and labelled B2M were similar. Dialyser clearances were negligible with LF. With HF, clearances calculated from the blood and dialysate sides were 20 6 ml/min (n=18) and 11 + 5 mVmin (n=36), respectively. This difference may be explained by membrane B2M uptake.

Extracorporeal B2M clearance would need to be >4oml/min thrice weekly for 4 hours to match metabolic clearance. However achievement of this would only result in -5% of normal metabolic B2M clearance.

R.A.Odell, J.E.Moran, P.Slowiazcek, K. Schindhelm University of New South Wales, Kensington; St. Vincent's Hospital, Fitzroy; AUSTRALIA.



265 PROLIFERATION OF B LYMPHOCYTES I S ENHANCED BY 266 D e t e r m i n a t i o n of Pore Rad ius o f H o l l o w - F i b e r POYMER MEMBRANES: I N V I T R O STUDY D i a l y s i s Membranes by U l t r a f i l t r a t i o n

Blood-mater ia l i n t e r a c t i o n s cause hunioral and c e l l u l a r changes i n t h e blood. I n t h e p r e s e n t s tudy , LPS responses of sp leen c e l l s i n t h e presence of polymers were i n v e s t i g a t e d . Mouse sp leen c e l l s were c u l t u r e d with LPS and c e l l u l o s e a c e t a t e ( C A ) o r po lye thylene ( P E ) f o r 72 h r s . Before c u l t u r e , CA and PE s u r f a c e s were t r e a t e d w:th medium a lone , ( N O N E ) ; wi th niouse serum (SERUM); with mouse serunl and then wi th ant i -C3 Ab (ANTI-C3). RPMI-1640 c o n t a i n i n g mouse serum was used f o r c u l t u r e except SERUM group. P r o l i f e r a t i o n of t h e sp leen c e l l s was measured by 3H-thyniidine i n c o r p o r a t i o n , and ezpressed a s mean st.iniulation index (SI)? SEM ( n = 9 , n = 6 ) . Treatment: NONE * SERUM ANTI-C3 NO POLYMER*

CA PE 14.4 f 2 . 7 1 3 . l f 1 . 7 7 . 0 f 1 . 9

28.6 f3.1* 24.7 2 2 . 0 1 4 . 7 2 2 . 8 13.8f 3.2

Tho p r o l i f e r a t i v e responses t o LPS were markedly enhanced by contac t with CA but n o t with PE. F u r t h e r , t h e responses i n NONE ( C A I and SERUM ((:A) groups were s i g n i f i c a n t l y g r e a t e r than t h a t of ANTI-C3 ( C A ) groups (p<O.Ol). From t h e s e f i n d i n g , t h e fo l low conclus ions can be drawn. 1. Polynter membranes enhance t h e B c e l l p r o l i f e r a t i v e rpsponse t o LPS. 2. The enhancement obta ined with CF, r e q u i r e s t h e presence of mouse serum. 3 . The nii:!or niechanisni which may e x p l a i n t h e enhancement seems t o be r e l a t e d wi th coniplenlent C3 a c t i v a t i o n or. polynier s u r f aces . J . Oqanla, 2 . Murabayashi , K. Ogasawara, K . Onoe, ar.d T. Yuta I r s t i t u t e of Inmiunological 'Science and Facul ty of Er&qineering, Hokkaido Univers i ty

*

D i a l y s i s membranes w i t h huge p o r e s a r e s u i t a b l e f o r e f f i c i e n t r e m o v a l o f b e t a - 2 - mic rog lobu l i n from HD pat ients. However, cu r ren t e l e c t r o n mic roscopy i s i n c a p a b l e o f d i r e c t l y o b s e r v i n g t h e po res , so t h a t t h e d i a l y s i s membranes should be i n d i r e c t l y evaluated.

Constant pressure f i 1 t r a t i o n experiments were made using i n u l i n and p o l y e t h y l eneg l y c o l s w i t h v a r y i n g m o l e c u l a r w e i g h t s f o r 6 c o m m e r c i a l l y a v a i l a b l e d i a l y z e r s t o ob ta in f i l t r a t e f l u x and s i e v i n g c o e f f i c i e n t a t v a r y i n g transmembrane pressures . The v e l o c i t y v a r i a t i o n method was used t o determine r e a l s i e v i n g c o e f f i c i e n t from which r e f l e c t i o n c o e f f i c i e n t was o b t a i n e d based on t h e method o f S p i e g l e r and Kedem. We then c a l c u l a t e d p o r e r a d i u s f r o m r e f l e c t i o n c o e f f i c i e n t data by the pore model.

C e l 1 u l o s i c and p o l y v e t h y l r n e t h a c r y l a t e membranes f o r c o n v e n t i o n a l d i a l y s i s t reatments ranged i n pore rad ius from 2 t o 3nm. Values f o r po re r a d i u s were i n s e n s i t i v e t o t h e m o l e c u l a r we igh t o f p o l y e t h y l e n e g l y c o l . The p o r e r a d i u s ob ta ined w i t h p o l y e t h y l eneg lyco l d i f f e r e d from t h a t w i t h i n u l i n because o f d i f f e r e n c e s i n mol ecul a r geometry.

T h e s e r e s u l t s d e m o n s t r a t e l h a t t h e d e t e r m i n a t i o n o f p o r e r a d i u s o f d i a l y s i s membranes f rom s i e v i n g da ta i s f e a s i b l e and usefu l f o r opt imal design o f d i a l y s i s membranes.

. . . e l - i c h i Ooaqdlyara, Kiyotaka Sakai

Dept. o f Chemical Engineering, Waseda Un ive rs i t y

267 TUMOR NECROSIS FACTOR a(TNFa) LEVELS I N SYNOVIAL 268 DIFFUSION CHAMBER FOR A BIO-ARTIFICIAL PANCREAS F L U I D OF PATIENTS ON HEMODIALYSIS(HD) WITH ARTHROPATHY

complicat ion of p a t i e n t s on long-term HD. We have e a r i l i e r r e p o r t e d t h a t it i s n o t m y l o i d d e p o s i t i o n b u t s y n o v i t i s and t h e subseqvent inflammation which t r i g g e r amyloid o s t e o a r t h - ropathy. TNFa r e p o r t e d l y has powerful bone r e s o r p t i o n , and causes product ion of co l lagenase and PG E2 i n synovia l c e l l s . I n t h e p r e s e n t s t u d y , we measured TNFa i n t h e s y n o v i a l f l u i d i n 10 HD p a t i e n t s s u f f e r i n g from swollen j o i n t s .

Measurement of TNFa was done by means of enzyme-immunoassay from Asahikasei . TNFa a c t i v i t y was found i n seven of 10 p a t i e n t s , w i t h a mean va lue of 1 . 5 2 f 0.96 u / m l . The Bz-microglobulin ( B z r n ) concent ra t ion of s y n o v i a l f l u i d i n 10 p a t i e n t s was 29.4 i 9 . 8 mg/l. There was no c o r r e l a t i o n found between t h e TNFa and Bnm l e v e l s . We suspec ted some c o n t r i b u t i o n of TNFa t o t h e a r thropathy . F u r t h e r s t u d i e s w i l l be devoted t o t h e r e l a t i o n between TNFa l e v e l s and X-ray f i n d i n g s of t h e j o i n t s .

Amyloid o s t e o a r t h r o p a t h y is a s e v e r e

Hi-pxhi Ogawa, Masataka Ono, Akira S a i t o , Y o s h i f u j i Matsumoto* S h i n s e i k a i Dai-Ichi H o s p i t a l and *Nagoya C i t y Un i i l e r s i t y , Nagoya, Japan

An implantab le d i f f u s i o n chamber f o r a bio- a r t i f i c i a l endocrine pancreas (Bio-AEP) was c o n s t r u c t e d by p l a c i n g p s e u d o - i s l e t ( i s l e t - l i k e c e l l c l u s t e r s : I C C s ) i n an e x t r a c e l l u l a r m a t r i x i n t h e c e n t e r of a r i n g h o l d e r sandwiched between two p o l y e s t e r membranes(pore s i z e : 0 . 2 ~ ) . which were h e l d i n p lace by t w o o t h e r r i n g h o l d e r s .

W e p rev ious ly d e s c r i b e d a method i n which neo- n a t a l p i g p a n c r e a t i c i s l e t - l i k e c e l l c l u s t e r s ( I C C s ) were embedded i n a n e x t r a c e l l u l a r mat r ix f o r long-term maintenance. Neonatal p i g pseudo- islets were formed from s i n g l e c e l l s of p i g pancreas i n suspension c u l t u r e and embedded i n an e x t r a c e l l u l a r m a t r i x mede from peps in-so lubi l ized type I co l lagen . When t h e I C C s were c u l t u r e d i n t h e gel-matr ix , they s u r v i v e d and func t ioned f o r a long-term c u l t u r e p e r i o d i n t h e presence of nicot inamide. Four hundred I C C s were maintained i n a n e x t r a c e l l u l a r mat r ix .

F ive s t r e p t o z o t o c i n (STZ) induced d i a b e t i c r a t s rece ived Bio-AEPs c o n t a i n i n g p ig I C C s (xenograf t - i m p l a n t a t i o n ) . A l l r a t s of STZ d i a b e t i c s w i t h Bio-AEPs surv ived wi thout any immunosuppressant f o r 4 weeks whi le STZ d i a b e t i c r a t s which had rece ived a chamber wi thout I C C s ( c o n t r o l ) d ied w i t h i n 14 days.

u s e f u l f o r t h e i m p l a n t a t i o n of xenograf ic i s l e t s i n d i a b e t i c animals and may open a new f i e l d i n t h e therapy of human IDDM.

Hisako Ohgawara, Sachiyo Nish i j ima, Naomi Mochi- z u k i , Yukimasa H i r a t a . Diabetes Center , Tokyo Women's Medical Col lege Tokyo 1 6 2 , JAPAN ~

Our r e s u l t s i n d i c a t e t h a t t h e Bio-AEP should be

Arrificiaf Organs, Vol . 13, No. 4, 1989


269 THE EFFECTS OF PLASMA EXCHANGE ON HEPATIC CELLU- LAR METABOLISM (REDOX STATUS) Plasma exchange(PE) h a s been widely a p p l i e d for t rea tment of h e p a t l c f a i l u r e . However t h e r e were few re: .or ts concern ing t h e e f f e c t of PE on hepa- t o c y t e s . The p r e s e n t s iudy was undertaken t o e l - u c i d a t e t h c e f f e c t s o f PE on h e p c t i c c e l l u l a r energy metzbol i sns( redox s t a t u s ) . M a t e r i a l s and methods: Eleven a c u t e b e p a t i c f a i - l u r e d p a t i e n t s t r e a t e d i n 1968 were s t u d i e d . PE was performed f i f t y t imes on those p a t i e n t s . Approximately 3000ml of- f r e s h f rozen plasma(FFP 1 w a s used a s replacement f l u i d s . A r t e r i a l blood was taken a t s tart of PE, one hour and 24 hours a f t e r PE. Acetoace ta te (Ac-Ac) , B-hydroxybutyrate ( 8 - O H B ) , pyruvate and l a c t a t e were measured and then ketone body ratio(KBR=Ac-Ac/B-OHB) and py- r u v a t e / l a c t a t e ( P / L ) were c a l c u l a t e d . KBR and P/L n f FFP were a l s o measur-ed. Resu1ts:The v a l u e s of KBR and P/L were a s f o l l o w s

p r e PE l h r a f t e r PE 24hr a f t e r PE KBR 0 .649+0.087 0 .636i0 .223 O.713tO.241 P/L 0 .073t0 .021 0.084iO.025 0.08OtO.019

PE d i d not change t h e v a l u e s o f K B R and P/L s i g - n i f i c a n t I y d e s p i t e t h e f a c t t h a t KBR o f FFP ( 0 . 1 8 2 t 0 . 0 8 5 ) was s i g n i f i c a n t l y lower than those of a r t e r i a l blood. Conculs ion: I n view of no s i g n i f i c a n t change i n KBR and P/L, PE d i d n o t appear t o a f f e c t redox s t a t u s of t h e h e p a t o c y t e s . Though approximate ly 3OOOml of FFP was r e p l a c e d , t h e va lue of K B R r e - t u r n e d t o t h e pre PE l e v e l . T h i s f a c t s u g g e s t s t h a t PE caused d r a s t i c change i n metabolism o f Ac-Ac, B-OHB and subsequent ly t h a t of K B R . Yoshio Ohtake, Hiroyuki Hirasawa, Takao S u g a i , Shige to Oda, Hide tosh i S h i g a , Department of Emergency and C r i t i c a l Care Med., Chiba U n i v e r s i t y School o f Med., Chiha , Japan

271 A NEW PERFLUOROCHEMICAL EMULSION: AN OVERVIEW

A s d i s c u s s e d elsewhere, a mixed PFC emulsion (Fluosol@' ) has room f o r improvement from t h e a s p e c t s , e . g . , of t h e s t a b i l i t y : The emulsion must be f r o z e n f o r long-term s t o r a g e , one of t h e PFCs used i n F l u o s o l shows somewhat s m a l l e x c r e t a b i l i t y and a p e c u l i a r s i d e e f f e c t such as a c u t e blood p r e s s u r e f a l l found i n dogs , even though t h e r e a r e found t h e l a r g e number of c l i n i c a l success . W e have t h u s developed a more i d e a l PFC emulsion: P e r f l u o r o N-methyldecahydro- i s o q u i n o l i n e (FMIQ) emuls ion , which can be s t o r e d i n a l i q u i d s ta te f o r 2 y e a r s and e x h i b i t s r e a s o n a b l e e x c r e t i o n rate and no complement-related r e a c t i o n i n dogs. We have a l s o succeeded i n t h e exchange- t ransfus ion w i t h t h e FMIQ emulsion in rats. These p r e c l i n i c a l s t u d i e s i n d i c a t e t h a t t h e FMIQ emulsion would show t h e s a m e o r g r e a t e r c l i n i c a l e f f e c t s compared t o F l u o s o l . Mention w i l l be made on exper imenta l r e s u l t s of our r e c e n t s t u d i e s .

H. Ohyana i, Y. S a i t o h , T. Mitsuno, M. Watanabe,* K. Yamano:chi* and K. Yokoyama,* F i r s t Dept. of Surgery , School of Medicine, Kobe U n i v e r s i t y , Kobe, and *Green Cross Co., Osaka, Japan

270 PERCUTANEOUS CARDIOPULMONARY BYPASS EXPERIMENTAL, AND PRELIMINARY CLINICAL USE

We r e p o r t a new percutaneous cardiopulmonary bypass (CPB) system us ing a modi f ied S e l d i n g e r technique for emergency use . Arterial i n f l o w w a s e s t a b l i s h e d through one femora l a r t e r y w i t h an end-hole 14 F r s h e a t h and out f low percutaneous ly through one femora l v e i n w i t h a mul t i - s ide-hole 24 Fr shea th . I n s e r t i o n w a s smooth and the system could be r a p i d l y a p p l i e d by anyone familiar w i t h percutaneous c a n n u l a t i o n . An e r p e r i n e n t d stuc?y wi.21 mongrel dogs demonstrated t h a t t h e mean maximum CPB f l o w wi th one venous c a n n u l a t i o n was 65ml/kg. Although n o t y e t p e r f e c t e d i n terms o f a c h i e v a b l e f low r a t e s , t h e technique of percutaneous CPB c m p r o v l d . ~ teaporar j . l i f e s a v i n g t h e r a p y u n t i l d e f i n i t i v e therapy can be i n s t i t u t e d . C l i n i c a l cases have involved t h o s e p a t i e n t s r e s u s c i t a t e d f o l l o w i n g r e f r a c t o r y c a r d i a c c o l l a p s e a w a i t i n g LMT PTCA therapy .

H i t o s h i Ohteki , Hisao Suda, Tsuyoshi I t o h , Eept . o f Thorac ic & Cardiovascular Surgery , Saga Medical School , Kyoj i Kohchi, H i r o a k i N o r i t a , Nobuhiko Koga, Koga H o s p i t a l , Kurume

272 WF'ECI? OF PLASMA MClBNGE ON OPS5iIZATION ACTIVITY OF SERAANDNEUIR0PHII.S PHAKXXl'ICFUNI?oN I N HEPATIC FAILLIF37 PATIENTS.

Serious infection has been implicated as the rain cause of death in 11% of hepatic failure(HF) patients. In this study, opsonization activity of sera and neutrophils phagoqkic function, a vital ccmponent of host defense against infection, in HF patients were studied so that the efficacies of plasma exchange(PE) could be evaluated.

Eight patients were included i n this study. PE with fresh frozen plasm was carried out on these patients. Neutrophils(NPs) phaqoqtic function and opsonin index were examined before and after each PE procedure. NPs function was assessed by ch&luninescence(CL) to z p z a n particles. @so- nization activity of sera was measured fran peak CL of normal NPs in respnse to zymozan particles which had been opsonized w i t h either HF patients sera or normal Sara. Opsonin index was calculated as the ratio of opsonization activity of HF sera to that of n o m l sera.

NPs phagocytic function before and after PE were 1.61+0.16 and 2.27+0.65 CL/cell( mean+S.D.), respectively. A significant increase in PNs function was seen after PE. Although, HF patients shaved a decreased opsonin index, the index was increased significantly by PE. The index before and after PE were 65.0+23.1 and 74.0+25.4(pd0.05).

PE with fresh frozen plasm improves neutraphils function and opsonization activity, suggesting not only a favorable aspect of PE in HF treatment but also an applicability of PE in the care of other critical cnnditions. K.Okab=, J.Mikuni, K.E&uhara, T.Tanabe, M.Suzuki, L.Hashimoto, S.Matsubara, K.Ouchi, S.Matsuno. ist.Dept.of S u r q q , Tohoku univ. Sendai, Japan.

Artificial Organs. Vol. 13. No. 4. 1989


273

275

CLINICAL EXPERIENCE OF THE MECHANICAL CIRCULATORY ASSISTANCE FOR THE FAILIKG HEART

Intraaortic balloon pumping (IABP) has been widely utilized clinically as a means of mechanical circulatory assistance (MCA). However there have been a few patients whc could not be saved from profound heart failure before and after cardiac surgery in spite of ZABP assistance.

and LVAD has been employed in 184 patients with cardiogenic shock, low cardiac output sydrome after cardiac surgery. They consisted of 165 cases of IABP assistance, 15 cases with IASP+V-A bypass and 4 cases of LVAD. Subsequently, 131 cases have been weaned from the MCA. And the remaining 116 cases (63%) have been survived.

of 15 cases IAEP+V-A bypass and 2 out of 4 cases consisting of ventricular rupture such as combined valvular heart disease were weaned from each circulatory assistance. From these clinical experiences, the efficacy of the LVAD was clearly confirmed hemodynamically in comparison with IABP and IABP+V-A bypass. Selection of the type of the MCA should be based on the severity of the cardiac failure. At present, it was a great problem t o avoid multiple organ (kidney, liver, lung) failure during and after initiation of IABP or IABPfV-A bypass and temporary use of the MCA might be recommended as a bridge to heart transplantation.

Masayoshi Okada, Naki Kubota, Masanao Imai, Yoshihiko Tsuji, Masato Yoshida, Takuro Tsukube, Yuichiro Mukai, Shinichiro Yamamoto, Katsuya Hisnno, Shuichi Kozawa. Kazuo Nakamura: Kobe Univ. 1ln;pital. Dep. of Surg. Div. 11 Kobe, Japan

Until now, the MCA such as IABP,IABP+V-A bypass

That is, 114 out of 165 cases with IABP, 7 out

EFFECT OF PLASMA PERrmSIoN OVER ?Xl!XlRBEBT ON THE IMWbDmIW STATUS IN ORSIRUc?TIVE JAUNDICE Immunological functions are deteriorated in ob-

structive jaundice. This study is to evaluate the effect of remwal of plasma biliary solutes using a resin adsorbent on the irrnrmnological status in the jaundiced dog model. Jaundiced dogs were surgically created and divi-

ded into three groups. The true group was treated by 10 sessions of plasma perfusion over an anion exchange resin and the sham group was treated without adsorbent. The control had no treatment. Biochemical and hematological parameters and the chanqes of lymphocyte transformation reactivities (LTRs)to mitogens(PHA,PWM,conA) were studied.

bilirubin agd cholyqlycine were increased in the control and sham groups, while those in the tnie group sh& slight decreases with siqnifi- cant reductions after each treatrnent(4mg/d1,4.8mg/ dl).The LTRs in the control and sham qroups showed lymphocyte functions toke suppressed, while those in the true group were maintained well at 90% during the course of treatment. The post treatment plasms were less suppressive to normal LTRs than those frm the control and sham dogs. The LTRs of plasm treated in vitro by resin on normal lymphocytes were increased with the increasing amount of the resin sorbent and the plasm treated in vitro sh& lower bilirubin and cholyglycine levels. 'fie results suggest that treated or non

jamdiced plasmas were less suppresive for the normal lymphocytes and that plasma perfusion over adsorbent in the jaundice is effective in improving the deteriorated lynphocyte functions. S.cmokawa, P.S.Malchesky*, Y.Nose*, Y.Asanm, K. KO-, Department of Surgery, Akita University, A k i t a , J a w , *Department of Artificial Organs, The Cleveland Clinic Foudation.

'Ibtal

274 BIOCOMPATIBILITY OF UV-IRRADIATED CO APATITE- COLLAGEN COMPOSITES FOR SOFT AND HARD TISSUES

3

Apatites have been applied in dentistry to fill up resorbed bone after tooth extraction and in defective areas of mandibular bone. However, conventional block-type apatites are difficult to process into complex form and granular-type apatites do not readily retain the required form. Furthermore, most commercial hydroxyapatites are sintered, and their chemical properties differ somewhat from those of biological apatites.

In this study, CO apatite with chemical composition (Ca=35.9%, P=16.5%, CO =3 .9%) and crystallographic properties (Fig.) similar to those of bone was synthesized at 60°C and pH 7.4. To obtain better handling properties, the apatite powder was mixed with collagen solution, whose antigenisity had been removed by enzymatic treatment, and formed into apatite-collagen pellets. After insolubllization by UV-irradiation for 4 hr, the composites showed remarkably reduced disintegration in 0.9% NaCl solution. When the composites were implanted surgically beneath the skin and the periosteum cranii of rats, they showed good biocompatibility. The UV-irradiated sample kept its features well and was packed with newly created material 2 or 3 weeks after implantation in both soft and hard tissues.

3 3

5"%..,r

2 2 Fig. X-ray diffraction 20 25 30 35

patterns of CO Ap and bone. POI.) Masayuki Okazaki, 3 Hiroaki Ohmae, Tsunenori Hino*

Osaka University Faculty of Dentistry, Osaka, and *Research Institute for Production Development, Kyoto, Japan

276 IbMJKKlmm EFFECl's OF MRXRIAL VI'JRO EVAWATION ON COMPLEMENT ACYIWWION AND

Blood-mterial interadions during extracorpsre- a1 circulation cause hmral changes that may mxl- ulate the i m m e respnse. An in vitro &el was studied to assess immunomodulating effects as a result of serum material interactions. Five normal sennns were perfusd through the control circuits or mini-modules made of polyvinyl alcohol (PVA) or ethylene vinyl alcohol copolymer(EVAL)(tms 4~ or D). Percent reductions of total protein, albumin, Ig and total cholesterol were 518% for PVA, and <5%forEVALmcdules. C3andC4were significantly decreased and C3a, C4a and C5a were elevated to 51107,16975 and 28ng/ml respectively for rmA,while the EVAL modules showed minimal changes. Proli- ferative responses of lymphocytes to mitogens conA,PwL,PWM and Candida were measured. The serums passed through the WA significantly suppressed lymphocyte proliferations,while the EvpL-4~ serums showed a sliqht enhancement for COnA and PHF~

-IN ITS INEvLuETJ(3E ON LYMPIH)(NTE RESPONSES-

--- Net B M of -Lymphocyte Wansfomtion Studies Fre control WA EYAL-IA EVAI-D

Con A 42072 39607 0 48240 42891 PHA 68176 52343 814 72024 62765 rn 13906 11675 232 12816 11912 W i d a 19993 19943 170 21434 20590 Qch membrane material had a different impact on

the immune response and the PVA was the most inmiunosuppressive. Amphylatoxins were suggested to cause the suppression. k m m e respnses can be modulated by membrane devices without the use of specially designed biologicals. S.cknokawa, P.S.Malcheskyk, Y.Nose*, Y . A s a n m , K. Koym, Department of Surqery, Akita Akita, Jpan, *Department of Artificial Organs. The Cleveland Clinic Foundation.

University,



217

279

POROUS HYDROXYAPATITE FOR CARTILAGE INTERFACE

ability to bind directly to bone. The purpose of this experimental study is to evaluate the histocompatibility of HAP for cartilage tissue in vivo, and in vitro( without inflammation).

In vivo study, HAP chips were made of synthetic macroporous(pore size 100-300um)HAP with micropore(pore size 5-1 5um) .Chips were implanted at the cervical tracheas of 6 mongrel dogs. After observation for more than 36 days, dogs were sacrificed. In vitro study,HAP round plates were prepared for organ culture. Cartilaginous femura were taken from 9 day chicken embryos and were placed on the HAP plates and in BCjb F-T Mod. medium supplemented 10% chicken embry- onal extract,Vit D3,PTH incubated at 37°C in a humidified air w i t h 5% GOLOrgan culture maintained from 6 to 8 days. Specimens were fixed in 2.5% glutaraldehyde solution and prepared for light microscopic(LM) and SEM examination.

all chips HAP were anchored firmly to tracheal cartilage and ingrowth of cartilage tissue into HAP macropores were observed as a mechanical interlock by LM examination. SEM observation of the cut surface made it clear that proteins on the HAP surface was removed,and etching of HAP grain boundaries occured as a sign of resorption.

into HAP pores, recognized both in in vivo and in vitro studies, is considered to be the main cause of good histocompatibility of HAP. K.Onishi,T.Takahama,F.Kanai,Y.T.Yoshitake Hiraishi,Y.Idezuki,A.Furuse,N.Nakabayashi 1st Dep.of Surg.Saitama Med.Ctr.Saitama Med.Col1. Univ.of Tokyo,Tokyo Med.Dent.

Hydroxyapatite(HAP) ceramics have the unique

In the specimens of in vivo and in vitro study,

In conclusion,ingrowth of cartilaginous tissue

CLINICAL APPLICATION OF LEFT VENTRICULAR ASSIST DEVICE (LVAD) :RETROSPECTIVE EVALLJATION OF MULTIPLE ORGAN FAILURE (MOF)

In our clinical LVAD cases, we performed comparative studies on 4 MOF cases, and 2 non-MOF cases. Pre-operative major organ (heart, lung, kidney and liver) function, hemodynamics during LVAD support, pre-weaning major organ function were evaluated retrospectively.

between MOF group and non-MOF group. During LVAD support, MOF group had significantly lower total cardiac out-put, and higher left atrial pressure, central venous pressure than MOF group.

Non-MOF group could successfully wean from LVAD, in a satisfactory condition;CI 2.51/min/m, PCWP 15mmHg. This hemodynamic state was considered to be weaning criteria of LVAD. In pre-weaning, MOF group had slight deterioration of renal and liver function.

In addition, it was noted that start of LVAD support had tend to delay in MOF group.

The results suggerst that, to avoid MOF, cardiac out-put have to keep high level, during LVAD support, and weaning timing have to be carefully decided, refering to evaluation major organ function.

Pre-operative major organ function was simillar

Yukihiko Orime, Takamitsu Hasegawa, Shinzo Kitamura, Masato Ohhira, Shoji Shindo, Motomi Shiono, Hiroaki Hata, Yasushi Harada, Yukiyasu Sezai The 2nd Department of Surgery, Nihon University School of Medicine Tokyo, Japan

278 RECIONAL BLOOD FLOW AND METABOLISM IN BRAIN DURING PULSATILE AND NON-PULSATILE PERFUSION UNDER PROFOUND HYPOTHERMIA WITH TOTAL CIRCULATORY ARREST In 39 mongrel dogs, regional cerebral blood flow

(CBF) and cerebral metabolism (A-V 0 difference and excess lactate) were measured under pulsatile and non-pulsatile cardiopulmonary bypass with total circulatory arrest at 20 C cerebral temperature ( f o r 40 minutes in 1 5 dogs, 60 minutes in 12, and 80 minutes in 12). CBF in both groups decreased as cerebral temperature lowered with no significant difference between the two groups during the cooling period. A-V 0 difference in both groups also decreased and it tended to be higher in the pulsatile group than that in the non-pulsatile during the cooling period. After the circulatory arrest for 40 minutes, as cerebral temperature increased to 35 C, CBF in both groups returned to the values as high as respective initial values. And A-V 0 difference in the pulsatile group also returned, but it did't return in thmon-pulsatile group. After thecirculatory arrest for 60 minutes, CBF at 35 C in the pu,ulsatile group increased to 141.8% of its initial value, but it remained lower(64.5X) in thenon- pulsatile and was significantly lower than that in the pulsatile. After the circulatory arrest for 80 minutes, CBF in both groups remained lower than respective initial values. These results suggest that pulsatile perfusion maintains the good cerebral aerobic metabolism and regional cerebral blood flow, and that it could protect the brain from ischemic and hypoxic damage caused by profound hypotherrnia and total circulatory arrest. Masahiko Onoe, Atumi Mori, Ryoko Tabata, Syoji Watarida, Syoitiro Shiraishi The Second Department of Surgery, Shiga University of Medical Science, Shiga, Japan

280 COMPARISON OF VARIOUS TYPES OF RATE RESPONSIVE PACEMAKER

The ideal pacemaker would be one which increases pacing rate appropriately according to metabol ic demand. We implanted seventy eight rate-responsive pacemakers (RR-PM) of various type and compared them to the data from normal healthy volunteers. The pacemakers included 5 QT sensors, 14 activity sensors, 13 blood temperature sensors, 46 respiratory rate sensors. We measured respiratory rate, oxygen consumption, carbon dioxide production & respiratory quotient to evaluate the respiratory function and used ejection fraction & cardiac output to evaluate cardiac function using a computerized cardiac nuclear probe at rest and during an ergoweter exercise test.

In healthy volunteers, the time interval between the start of exercise and increase in respiratory rate, heart rate and oxygen consumption were 144t15, 6626. and 66+6 sec respectively. Activity sensor PM showed fastest rate response. The temperature sensor PM showed the faster response than volunteers. The QT sensor PM showed the slowest response. The respiratory sensor PM also showed slower response but varied pacing rate most satisfactorily according to respiratory metabolic demand. Every type of RR-PM improved cardiac function during exercise.

A1 though respiratory responsive PM showed most satisfactory rate response function, any single sensor RR-PM has limitation judging from the data from healthy volunteers. Shin-ichi Osaka, Shigeo Tanaka. Hiroki Hosaka, Noriyoshi Kutsukata, Toshio Fukushima, Tasuku Shoji, Department Thoracic Surgery, Nippon Medical School, Tokyo, Japan

Artificial Organs, VoI. 13, No. 4 , 1989

ABSTRACTS OF THE

281 A N E W ANTIPLATELET AGENT(E5510)-MORE EFFECTIVE TO REDUCE RESIDUAL BLOOD VOLUME I N HEMODIALYSIS

A newly developed a n t i p l a t e l e t agent (E5510) , compared wi th c o n v e n t i o n a l one, i n h i b i t s p l a t e l e t a g g r e g a t i o n and s u p p r e s s e s p l a t e l e t adhes ion and release r e a c t i o n . A m u l t i c e n t e r c o l l a b o r a t i v e s t u d y was des igned t o e v a l u a t e t h e e f f e c t of t h e drug on reducing t h e r e s i d u a l blood volume i n HD c i r c u i t . Thi r ty-n ine HD p a t i e n t s ( p t s ) wi th hyper- c o a g u l a b i l i t y w e r e d i v i d e d i n t o t h e fo l lowing subgroups f o r c ross -over s tudy . Group Observ. 1st P e r . Washout 2nd P e r . F0110w-u~

283

Per(1w) (lw) P e r . (lw) (lw) P e r . (lw) I (n=21) x 2 mg x 4 mg X

I I ( n = 1 6 ) x 4 mg x 2 mg X The d r u g was a d m i n i s t e r e d o r a l l y l h r b e f o r e t h e i n i t i a t i o n of h e m o d i a l y s i s . Dosage of h e p a r i n was not changed d u r i n g t h e s tudy .

Dosage Improve. Suppress . TxB2 a-ketoPGF1, (mg) of c l o t i n p l a t e l e t (pg/ml) (pg/ml)

c i r c u i t ( % ) a g g r e g ( % ) - I 2 52 .4 73.3 98.3 138 .4 I 4 57 .9 64.3 85.0 121.5 I1 2 50.0 60.0 98.9 1 2 4 . 2 I1 4 56 .3 58.3 90.9 114 .5

t o reduce t h e r e s i d u a l blood volume i n HD c i r c u i t i n more than 5 5 % of HD p t s wi th h y p e r c o a g u l a b i l i t y .

Our r e s u l t s s u g g e s t t h a t t h e drug w a s e f f e c t i v e

VlIth WORLD CONGRESS 353

K . Ota,T. Suzuki , S .Teraoka,Y .Fuj i ta l ,Y .Hirasawa2 S . Koshikawa,T .Akizawa3 ,N.Mimura4 , A . S a i t o 5 , T .Sakai6 , Tokyo Women’s Medical College,Tokyo,Japan,lHyogo Med.College,2Shinrakuen Hosp. ,3Showa Univ. , 4Totrnnomon Hosp. , 5 S h i n s e i k a i Hosp. ,6Ki taza to Univ.

CLINICAL TRIAL OF A NEW ORAL PHOSPHATE AD- SORBENT PHOSTAKE A(PT-A)

Administration of conventional aluminum hydroxide gel for control of serum phosphate is found to be unsatisfactory because of side effects such as disturbance of bone metabolism and encephalopathy. For the benefit of the patients, we developped boehmite form aluminum hydroxide(PT-A), which is hardly soluble to digestive juice.

The chemical formula is AIO(0H). The concentration of activated OH groups on the PT-A surface is 0.2-l.OmEq/g, and the relative surface area is over 200myg. The study candidiates were 15 patients with chronic renal failure. All of the 15 patients took PT-A, 3 times after meals. The daily dose was 1.5, 3.0. and 6.0g.

The serum P level was 6.5i1.5mg/dl before treatment, 6.5fl.Zmg/dl a t second months and 6.4 fl.2mg/dl at 3rd months of treatment by PT-A, revealing no rise, in particular, of the serum P level. The blood A1 level was 10f9.0 p / d l before treatment with a drop to 6.4*6.5$g/dI in the second month of treatment and 5.2+3.6pg/dl a t 3rd m o n t h s .

The Al in alurninum gel is dissolved by lhe gastec juice (strong acid) and is ionized. It then combines with P to form the non-soluble aluminum phosphate and removes P from the digestive fluid. On the other hand it is thought that PT-A does not become ionized and eliminates P by physical adsorption.

W e believe that the newly develop P adsorbent, PT-A is seems to be effective to avoid aluminum osteopathy and encephalopath y.

0 Otsubo, Y .Suzuki, T.Yanagisawa, H.Tsuji, K.Kuzuhara, S.Hara, Y.Ogura, T.Suzuki*, M.Kabayama*, S.Otsuka*, N .Takai**, Nephrology Center, Toranomon Hospital, *Tomita K K., **Institute of Industrial Science, Univ. of Tokyo

282 PROSTHETIC VALVE ENDOCARDITIS -ANALYSIS OF THE OUTCOME AND THE REINFORCING SURGICAL TECHNIQUE -

This paper shows t h e c l i n i c a l e v a l u a t i o n s of p r o s t h e t i c v a l v e e n d o c a r d i t i s (PVE). PVE occur- r e d i n 17 c a s e s (4 .3%) among 440 c a s e s of v a l v e rep lacement .

PVE was e v a l u a t e d a s f o r t h e microorganism, c o m p l i c a t i o n , o p e r a t i v e i n d i c a t i o n and o p e r a t i v e m o r t a l i t y . A l l o f PVE were c o n s i s t e d o f b iopros- t h e t i c PVE 5 c a s e s and mechanical v a l v e PVE 12 . Microorganism w a s s t r e p t o c o c c u s e p i d e r m i d i s i n a n overwhelming m a j o r i t y . O p e r a t i v e i n d i c a t i o n s w a s c o n g e s t i v e h e a r t f a i l u r e i n a lmost a l l c a s e s , n e x t t o v e g e t a t i o n and i n f e c t i o n r e s i s t a n t t o medica l t r e a t m e n t . M o r t a l i t y i n PVE w a s 53% (9 o u t of 17), b u t mechanica l v a l v e PVE w a s worse i n prognos is t h a n b i o p r o s t h e t i c PVE.

C e r e b r a l compl ica t ions occurred i n 4 c a s e s of mechanical v a l v e PVE, on t h e o t h e r hand t h e r e no c e r e b r a l compl ica t ion i n b i o p r o s t h e t i c PVE.

I A s f o r t h e hemodynamic change i n PVE, mechani- c a l v a l v e PVE had t h e tendency t o t a k e t h e prompt o r sudden d e t e r i o r a t i o n of hemodynamics caused by e n d o c a r d i t i s sur rounding t h e s u t u r e r i n g , espe- c i a l l y i n mi t r a l p o s i t i o n , on t h e c o n t r a r y hemodynamic d e t e r i o r a t i o n w a s g r a d u a l l y proceeded i n b i o p r o s t h e t i c PVE.

c i a l l y i n mechanical v a l v e PVE, i n which c a s e s e n d o c a r d i t i s w a s recognized o n l y sur rounding t h e s u t u r e r i n g . F i n a l l y , t h e r e i n f o r c i n g technique w i t h c o l l a r e d p r o s t h e s i s w i l l be shown f o r t h e PVE i n m i t r a l p o s i t i o n .

Masaki O t a k i , T a i c h i Miki , Akimitsu Yamaguchi, H i d e t o s h i Tamura, Nobuo Kitamura Dept. of Card iovascular Surgery , O s a k a Nat iona l H o s p i t a l , Osaka, Japan

UCG made much of t h e d i a g n o s i s of PVE, espe-

284 PROTECTIVE EFFECT, AGAINST HEWOLPSIS, OF PERFLUOROALKYXATED CBAINS IN SURFACTANTS

It was found t h a t s u r f a c t a n t s wi th a h i g h l y hydrophobic p e r f l u o r o a l k y l a t e d end, i n s p i t e of t h e i r s t r o n g l y i n c r e a s e d a m p h i p h i l i c c h a r a c t e r and s u r f a c e a c t i v i t y , can be c o n s i d e r a b l y less hemolyt ic than t h e i r hydrocarbonated a n a l o g s . T h i s w a s demonstrated on s e v e r a l d i s t i n c t s e r i e s of r e c e n t l y s y n t h e s i z e d f l u o r i n a t e d s u r f a c t a n t s d e r i v e d from s u g a r s , p o l y o l s and aminoac ids . For each h y d r o p h i l i c head , s u r f a c t a n t s having v a r i o u s l e n g t h s o f t e r m i n a l f l u o r i n a t e d c h a i n s and v a r i o u s l e n g t h s of hydrocarbonated pro longa- t o r s between head and t a i l were i n v e s t i g a t e d .

A s a r u l e , hemolysis was observed t o d e c r e a - se s i g n i f i c a n t l y when t h e l e n g t h of t h e f l u o r i n a - t e d p a r t i n c r e a s e s and when t h e s i z e and hydrophi- l i c c h a r a c t e r of t h e p o l a r head i n c r e a s e s ; i t i n c r e a s e s when t h e l e n g t h of t h e hydrocarbonated p r o l o n g a t o r i n c r e a s e s , t h e h i g h e s t e f f e c t u s u a l l y b e i n g observed i n t h e absence of f l u o r i n a t e d segments .

Such s u r f a c t a n t s a r e d e s t i n e d i n p a r t i c u l a r t o a l low t h e p r e p a r a t i o n and i n c r e a s e d c o n t r o l o v e r t h e p r o p e r t i e s of f luorocarbon emuls ions t o be used a s blood s u b s t i t u t e s .

S. PACE, J. G . RIESS and L. ZARIF L a b o r a t o i r e de Chimie Molbcula i re , Uni t6 de Recherche Assoc iee au CNRS, U n i v e r s i t e d e Nice, P a r c V a l r o s e , 06034 Nice-Cedex, France .



28s ACID-BASE BALANCE I N HIGH-FLUX HEMODIAFILTRATION.

The metabol ic f a t e of b i c a r b o n a t e p r e c u r s o r s i n f u s e d i n l a r g e amount d u r i n g a h e m o d i a f i l t r a - tion (HDF) seance was e v a l u a t e d .

We s t u d i e d i n 5 s t a b l e male p a t i e n t s on RDT t h e b u f f e r ba lance dur ing a s i n g l e midweek seance wi th a c e t a t e d i a l y s a t e (38 mmol/l) and l a c t a t e c o n t a i - n ing s u b s t i t u t i o n f l u i d (42 mmol/l);Qb=400 ml/min; Qd=800 ml/min;time 150215 min.Rlood (BpH)and i n t r a e r y t h r o c y t i c (IpH) pH,bicarbonate , blood g a s e s , l a c t a t e (LAC),pyruvate (PYR) and a c e t a t e (AC), anion-gap i n plasma and out f lowing d i a l y s a t e t o t a l l y c o l l e c t e d i n a t a n k (ODTC), were measured s t a r t i n g d i a l y s i s , a f t e r 1 h , ending d i a l y s i s , 1 h a? t e r complect ion and s t a r t i n g n e x t d i a l y s i s (ND).

During t r e a t m e n t BpH, IpH,Bicarbonate i n c r e a s e d from 7.35 t o 7.43; from 7.36 t o 7.4 and 2 2 . 8 t o 24.7 mmol/l and ND were 7.39,7.38 and 19.6 mmol/l. PO2 and PCO2 decreased not s i g n i f i c a n t l y d u r i n g t r e a t m e n t . Plasma AC r o s e from 0.081+0.07 t o 1 . 7 9 20.93 mmol/l; LAC from 0.86kO.054 t o 4.16k0.72; PYR from 0.079+0.02 t o 0.17+0.03 mmol/l (p=O.OOl). The masses o f b a s e s ( c a l c u l a t e d i n ODTC) were: AC 2005+621; LAC 475j149; PYR 19.2k9.7 mmol.Pat ients metabol ize meanly 281 m o l o f LAC and 1035 mmol of AC d u r i n g a s i n g l e d i a l - y s i s .

d r a s t i c d i a l y t i c t ime r e d u c t i o n and a c e t a t e b u f f e r . A good A-R balance i n mantained i n s p i t e of a

V.Pcnichi , M.Par r in i , k .F .Bianchi , G.Grazi, C. Cirami, E.Hontagnani, G.Fontana, M.Neri, R . P a l l a I1 Medical C l i n i c , U n i v e r s i t y of P i s a , P i s a , I t a l y

287 QUANTJRCATION OF V A L V U k R THROMBUS FORUATION IN BLOOD PUMPS BY POLAR COORDINATE MAPPING

The standardized reporting of valve-associated thrombus formation remains a challenge. A polar coordinate mapping technique (PChU) to quantiratively describe perivalvular thrombus formation was applied in the examination of prosthetic valves in paracorporeal assist devices.

The method begins by photographing the ups~eam and downsmeam views of freshly retrieved, mounted valves on transparency film. The valve images are then projected onto lox planforms of the valves and the boundaries of the observable thrombi are traced. The radial thrombus length (RTL) is then measured at 5 O increments and plotted on Cartesian C O O T ~ ~ M ~ ~ S as a function of polar coordinate. Mean RTL and incidence of thrombus (IOT) are calculated. Analysis of variance can then be used to test for differences in the length, incidence and pattern of thrombus formation between test groups. Example mappings are presented for 12 unifonnly oriented valves (Medtronic Hall-) renieved from six assist devices hat pumped for =24 hours while connected to calves without anticoagulation. - - WWSTAEAM UPSTREAM I RII.OZOfoOl I O T . O n f O m I R n - o m o t m 1 0 ~ - 0 4 6 ~ 0 m - 3 2 , ,.I.*lSEU, -

POLAR COORDINATES (degrees)

Even though the mean RTL and IOT were not different @>0.05), the patterns of di&ibution were distinctly different and correspond to valve design features associated with upsueam flow stagnation and downstream flow separation. This application of the PCMT demonstrates its effectiveness for standardizing the reporting of perivalvular thrombus formation. The effect of valve selection. anti-coagulant regime and other factors that influence thrombus formation can be quantitativeIy compared with the PCMT. Consequently, the PCMT could be a valuable assessment tool for efforts being made to reduce thrombosis in prosthetic blood pumps. G.PantaIos. S. Everett, S. Mohammad, G. Burns, K. Solen, L. Reynolds, D. Olsen U J f - U t a h LBE., Brigham Young Univ., Univ. of Illinois at Chicago

286 BETA-2-MICROGLOBULIN (B2M) REMOVAL I N CONVENTIO- NAL HEMODIALYSIS (HD) AND I N HIGH-FLUX HEMODIA- FILTRATION (HDF) .

Hemodialyt ic amylo idos is seems r e l a t e d t o B2M c o n c e n t r a t i o n ; however h igh B2M plasma l e v e l s may r e f l e c t no t o n l y reduced e l i m i n a t i o n b u t a l s o in- c r e a s e d product ion . I n 10 p t s i n RDT (5 i n HD with Cuprophan membrane -CU-,5 i n h igh f l u x HDF wi th Po lysu lphone -PS-) i n plasma ( s t a r t i n g - e n d i n g d i a l y - s i s ) and i n t h e out f lowing d i a l y s a t e t o t a l l y co l - l e c t e d i n a tank,B2M was e v a l u a t e d w i t h R I A method. HD:180 min. HDF: Qb=450 ml/min; Qd=ROO ml/min; Time 150+15 min. Plasma B2M decreased from 40.5i: 11.6 t o 18.6k5.2 mg/l i n HDF (p=O.Ol) and i n c r e a - s e d from 42.1218.2 t o 67.0T29.9 mg/l i n HD(p=O.Ol). Ending d i a l y s i s v a l u e s have been c o r r e c t e d f o r He. The t o t a l amount of B2M c o l l e c t e d i n d i a l y s a t e was 144.4+ 107 mg i n HDF and 7.06k2.3 (p=O.Ol) i n HD. A n e t product ion of 400 mg of B2M may be c a l c u l a - t e d i n CU-HD assuming a d i s t r i b u t i o n v a l u e s a s e z t r a c e l l u l s r water ;no g e n e r a t i o n i s observed dur ing HDF, where convec t ive and d i f f u s i v e modes a s s o c i a t e d ensure an h igh e f f i c i e n c y B2M d e p u r a t i v e tec- n ique . Fembrane t rapping-as d e s c r i b e d f o r PAN-may account t h e d i f f e r e n c e between plasma B2M reduc- t i o n and t h e amount recovered i n d i a l y s a t e .

These f i n d i n g s may have i m p l i c a t i o n i n preven- t i o n of B2M r e l a t e d amyloidos is and i n chosing t h e d e p u r a t i v e t r e a t m e n t .

288

V.Panichi , A.K.Bianchi, M.Par r in i , C . C i r a m i , G. G r a z i , N.Keri, E.Montagnani, G.Fontana, R.Pa l la I1 Medical C l i n i c , U n i v e r s i t y of P i s a , P i s a , T ta ly .

INFLAMMATORY REACTION PROTEINS CHANGES IN CHRONIC HEMODIALYZED PATIENTS.

In long-term hemdialyzed patients, development of carpal tunnel syndrome and/or arthropathy could result from repeated hemodialysis-induced inflammation.

We investigated eight inflamtory reaction proteins i. e. immnoglobulins (I@, IgA, IgM), transferrin (TRF). C-Reactive protein (CRP), proteinase inhibitor (alpha-1 PI), alpha-1 glycoprotein acid (AAG) and haptoglobin (HPT) in 35 patients (17 M C 18 F) with end-stage renal failure undergoing regular dialysis treatment (RDT) using 3 different types of dialysis membranes ( 8 patients on Cuprophan, 13 on Cellulose Acetate and 14 on Polyacrylonitrile AN-69). Their mean age was 56 f 13 years (range 25-79) and duration of dialysis treatment was 95 5 65 months (range 3-216). All patients had no clinical evidence of infection and none of them received either corticosteroids or non-steroidal anti-inflamnatoxy agents. Blood sanples were drawn from pstients inmediately before initiation of dialysis. Assays were performed by immunonephrelometry with specific antisera on automatic nephelomter analyzer [BNA-Behring-France).

For all patienta, whatever the membranes used, we observed no significant difference in serum levels of IgG, IgA, IgM, T W , CRP and HPT between healthy subjects and dialyzed patients. On the contrary, we obsesved a significant increase of AAG serum concentration (M f SD): 1.1 f 0.3 g/L vs 0.6 f 0.2 g/L-'(p < 0.001) and a significant decrease of alpha-1 PI : 1.9 f 0.3 g/L vs 2.7

As alpha-1 PI is the m i n elaatase inhibitor, decrease in serum concentration could be related to its consumption which results from the control of elaatase released by granulocytes during hernodialysis session. Although the function of AAG remains poorly underatood, serum AAG is increased in RDT patients and its level could be a suitable marker of chronic inflammation in RDT patients.

JiLJkuL, I. Marcillac , N. Luong, V. Atger, H. K. Man, N. Noatti. Biochem-Labs and Nephrology Dept. Broussais Hospital and Nephrology Dept. Necker Hospital, Paris, France.

* 0.8 g/L (p < 0.001).



289 HUMAN POLYMORPXONUCLEAR LEUKOCYTES OXYGEN METABOLISM IN UREMIC PATIENTS. A LONGITUDINAL STUDY.

The purpose of the study was to evaluate the influence of uremia in end stage renal disease (ESRD) patients before and after regular dialysis treatment (RDT) on the oxygen metabolism of hurrran ploymorphonuclear leukocytes (PMNs).

Blood samples were drawn on heparin from 5 patients before and after the first, the fourth and the tenth dialysis sessions. Dialyzers used are equiped with Cuprophan membrane.

PMNs were isolated immediately after blood collection by a two-step procedure using Ficoll Hypaque and polyvinylic alcohol. Oxydative metabolism was aasesed by 02 consumption, H202 production (Clark oxygen electrode) and -2 generation (reduction of ferricytochrome C) in the presence of 10 rrg/ml opsonized zymosan (02) and 30 pg/ml phorbolmyristate acetate (PMA) used as stimuli. Results obtained from 20 healthy subjects served as control.

In comparison with the control group, (1) -2 generation, 02 consumption and H202 production of PMNs from ESRD patients, increased by 175%, 111% and 43% respectively, when PMts were stimulated by OZ and increased by 2029 , 54%. and 1222 respectively, when stimulated by PMA; (2) 0+2 generation, 02 consumption and H202 production of PMNs from RDT patients, increased by 131%, 137% and 33% respectively, when stimlated'by OZ and increased by 146%. 57% and 109t respectively, when stimulated by PMA.

It is concluded that (1) oxygen metabolism of PMNs from ESRD patients is dramatically increased and (2) there ia no significant difference in oxygen metabolism of PMNs between RDT and ESRD patients. These data suggeated strongly that hernodialysis procedure has no effect on the PMNs oxygen metabolism abnormalities found in ESRD patients.

J-L., N. Luong. V. Atger, N.K. Man, M. Roch-Arveiler, N. Moatti, 0.. Raichvarg. Biochern.Labs and Nephrology Dpt, Broussais and Necker Hospitals and UA CNRS 595 Pharmacoly Cochin Hospital, P a r i s . France.

291 CONTROLLING FIBROUS CAPSULE FORMATION, THE SOFT TISSUE RESPONSE TO ION MILLED SURFACE STRUCTURES

The body's response to an implant and the ability to control that response requires a fundamental understanding of the interaction. A model was developed utilizing aerospace technology, ion thruster engines by placing precision ion- milled pillars onto silicone implants. This pillar structure is regularly arrayed with the following dimensions: 50u 1:5; lOOu 1:l; lOOu 1:5; 250u 1:2 and a smooth control (x:y diameter: height ratio). 140 implants were placed subcutaneously for one month in the rat. The histologic response was characterized as to fibrous capsule, vascularity, pillar penetration and classical vs nonclassical response. RESULTS: Surface microstructuring significantly alters soft tissue wouqd healing (Ps.01) with regard to capsule thickness, 3011th vs (control 131utllu) blood vessel proximity D.7uk1.5 vs (control 98ut8u) and vascularity 2.18 vs (control 1.15). Specific pillar structures are capable of projecting beyond the fibrous capsule without eliciting a granulo- matous response. In conclusion, micropillars can reduce capsule formation by a factor of 4. and enhance blood vessel proximity by a factor of 10. These results are highly significant when designing mass transport devices as well 21s providing a model to further study the tissue I-i'sponse at the implant tissue interface. The application is directly applicable to drug delivery devices and implantable sensors.

._ George Picha. Roger Drake? Ken Mayhan* Case Western Reserve University, *BaxterHealthcare Cleveland Metropolitan General Hospital, Dept. of Plastic Surgery, Cleveland, Ohio, USA.

290 THE SOFT TISSUE RESPONSE TO THE MEME POLYURETHANE (PU) COVERED SILICONE BREAST IMPLANT IN RATS.

performed in over 200,000 women. PU foam covered implants represent an alternative to traditional silicone implants. However, in spite of inhibiting capsular contracture, reported problems include contracture, degradation, delamination, and infection. This study characterizes in the rat, (n=324) implants of the Natural-Y PU foam: unbacked and silicone backed and extracted smooth silicone controls. Duration of implantation was 3, 7, 14, 28, 60 and 90 days, 6 and 12 months. RESULTS: Based upon percent volume, over 90% of the interface created by the foam in occupied by exudate at early time periods. This exudate inhibits cell migration thereby dramatically limiting collagen production and capsule formation in contrast to the control. The collagen which is present is oriented around the foam spicules. The fibrous exudate appears to alter the kinetics of wound healing by prolonging the initital events. In addition, fissuring of the foam and surface cracking is initiated at 28 days and further p r o - gresses at one year. Angiogenesis and vascularity within the foam is enhanced over the control. Furthermore, micromotion at the PU spicule interface gives rise to hemorrhage and hemosiderin formation. CONCLUSION: The porous implant represents a means for controlling the collagen deposition via surface microstructuring. Finally, surgical technique and site selection i.e. fascia1 vs adipose tissue, appear to directly modulate the degree of fibrosis and wound healing in the foam. George Picha, Jeffrey Goldstein, Erich Stohr Case Western Reserve University at Cleveland Metropolitan General HospitaZDept of Plastic Surg. Cleveland, Ohio, USA.

Augmentation and breast reconstruction have been

292 SPECIFIC SORBENT FOR LIPOPROTEIN (a)

Lipoprotein ( n ) - L p ( a ) is apopoprotejn- B-coiitaining particle xhich plays an important r o l ~ a s independent risk fnc- tor in the development of atherosclerosis.

We study a possibility of selective. removal these particles by nffinity c h r om a t o g r a p h y ,

Lpla) was purified by ultracentrifuga- tion and gel-filtration with subsequent use of the sample for sheep immunization. Antiserum was treated several times by LDLs for the removal of anti a p o - B antibodies. Anti apo--(a1 antibo-- dies were isolated by ~ m m o n i u m sulfate precipitation and ion --exchange chroma - tography. Purified antibodies were covalently bound to Sepharose CL-4B.

Human plasma was perfused through a small column containing this immunosor- bent. Adsorbed material was eluted by acid pH. We have found that this material is identical to native Lp(a) and i s free from other plasma compounds.

We suggest that this type o f sorbent may be used for selective removal of Lp(a) from human blood.

Pokrovsky S . X . . P h . D . , B e n e v o l e n s k a y a G F . , Afanasieva O.I..Adamova I . Y u . USSR Cardiology Reseach Center, Moscow



293 BRIDGE TO TRANSPLANTATION WITH AN IMPLANTABLE ELECTRICAL V E ~ I C U L A B ASSIST SYSTEM

The implantable Novacor left ventricular assist system (LVAS) has been used as a bridge to transplant (BTT) in 41 (35M, 6F) patients (pts) aged 20 to 66 (mean 4 6 ) years. noses included: ischemic end-stage heart disease ( I H D , ll), cardiomyopathy (CM, 16) and acute myocardial infarction (AMI, 11). Four pts (IKD 2, CM 2 ) are currently supported, one at 111 days (d). Pt weight ranged from 55 to 99 (mean 74) kg and body surface area was 1.57 to 2.23 (mean 1.91) m2.

cally stable with substantially increased (+60% mean) cardiac index (CI). Renal, hepatic and pulmonary function were improved. Significant right ventricular (RV) support was achieved through afterload reduction. Some pts, initially in biventricular failure, required transient ( < 6d) inotropic or mechanical (5 pts) RV support. LVAS implant duration ranged from 2 to 111 (mean 30) d. Pts were typically fully ambulatory in 3 weeks and fully rehabilitated prior to transplantation (tx).

deaths) underwent orthotopic cardiac tx. There were 4 early ( < 2d) and no late deaths. Mean follow-up is 13 (range 1-54) months and survival (82%) is consistent with routine tx. This study demonstrates that BTT using the Novacor LVAS offers a viable interim therapeutic option. In an era of donor limitations the expanding BTT experience provides a valuable window on the future for the fully implantable version of this LVAS. Portner PM, Ramasamg N, Miller PJ, Strauss Llt, JS Jassawalla. Novacor Div., Baxter Healthcare Corp., Oakland, Stanford Univ Wed Center, Stanford, California, U.S.A.

Preoperative diag-

Operative survivors (36 pts) were hemodynami-

Twenty-two pts (69% excluding 5 perioperative

295 Cell Attachment and GrowLh on Polyurelhane Surfaces

Fibrolastic-cell attachment and g r w t h characteristics of dif ferent

polyurathone (PU) f i lms were tested. These f i lms were prepwed by a

Ll~;sical solvent-casting procedure. By changing the cornposttion and

type o i casting solution i . e . . Uioxane. THF, DHF. DMF-THF. THF-

Dioxane, etc 1, f i lms wi th different physical and chemical bulk and

surface structures were obtained. Structural properties o f these

rilnij wert: iitvestigirted by scanning eltctrorie rnizruscme {SEfl) and

contact angle studies. In stationary cell culture tests. 3 mode! cel l

line. i e. PHK. were used. and the effects o f structural properties on

the cell behaviour were investigated. The rezul ts demonstrate that. i t

,s possible to achieve dif ferent cell respoiises by changing the

preparation conditions o i i t lms While the cell attachment IS faster on

prrrnus P?1 surfaces. al l smooth surfaces showed similar aanesiuf,

eetter prol i ferat ion of BHK cells were ohtained wi th PU f i lm- which

narc prepared wi th dto ian i solution

t i . PUiMT", C iE i iVAR" , M. KlKEPilTCI". k.1. SERGETCI", E.FIY<IN' * Marmara Gniversity, Chemistry Dept.. Istanbul. Turkey * Hdietteps University. Cheniiiai Enginrtering Dept., Ankara. Turkey

294 A TOTALLY llIpLANTABLe ELECTRICAL V E ~ C U I A E ASSIST SYSTEM: PEECLINICAL IIEADINEESS TESTING

The totally implantable, electrically powered, Novacor left ventricular assist system (LVAS) utilizes an unique, solenoid actuated, dual pusher- plate blood pump and belt skin transformer. After nearly two decades of development and subsystem evaluation, the total system is now undergoing preclinical device readiness testing.

Twelve complete systems have been on test in individual mock circulations (immersed in saline at body temperature). Continuously monitored, the systems are diurnally cycled by varying preload and afterload. Twenty-one years (mean 21 months) of LVAS operation have been accumulated to date, without failure. Four systems have passed the two- year goal, nine have exceeded 18 months and all have been longer than 15 months. The demonstrated reliability (2-year mission) of 86% at an 80% confidence level already exceeds the original target (80% reliability, 60% confidence).

Chronic in vivo evaluation includes a total system implant of 260 days. Normal LVAS function was documented by continuous hemodynamic monitoring. Hematology, blood chemistry and serum enzymes remained within normal limits and hemolysis was insignificant (< 5 mg%). Tether-free operation was demonstrated. At elective termination, autopsy and explant retrieval were unremarkable.

A s elective chronic implantation in patients with end-stage heart disease approaches, this vitro and in vivo experience demonstrates efficacy and preclinical readiness of the total system. PH Portner, JS Jassavalla, PE Oyer, DH LaForge, H Chen, PJ Hiller, J Lee, J Billich, HB Daniel, N Ramasamy. Novacor Div., Baxter, Oakland and Stanford Univ Med Center, Stanford, CA, U.S.A.

296 THR CHANGES OF STRUCTURE AND MECHANICAL PROPERTIES OF BIOPROSTHESIS AFTER 68 MONTHS FUNCTIOMINO

Seven b i o p r o s t h e s i s were examined a t pe r iods r ang ing from 6 t o 68 months. Fi- ve were e r i c a r d i a l t i s s u e v a l v e pros the- sis (PCBP and two p o r c i a l b i o p r o s t h e s i s (PB) t r e a t e d w i t h 0,625% plu t a ra ldehyde. The first 48 h o u r s t h e v a l v e s were s t a b i - l i z e d under p r e s s u r e 30 mm Hg. Microsco- p i c examin8tion of 6 t o 68 months va lves r evea led t h a t t h e PCB t i s s u e r e t a i n e d i t s o r f g i n a l a r c h i t e c t u r e , b u t t h e co l l agen bundles s t r i c k e d t o g e t h e r , w i t h v a c u a l i - z a t i o n and l a y e r e d c a l c i f i c a t i o n between them. I n 1 2 t o 36 months PB l e a f l e t s t h e c o l l a g e n bundles became rough. One va lve had rup tu red a r e a s o f t h e noncoronary cusp. There were p r a c t i c a l l y no changes o f e l a s t i c f i b r e s .

comes more e x t e n s i b l e and i t s u l t i m a t e s t r a i n i n c r e a s e s 2,5 t imes . U l t ima te s t r e s s d e c r e a s e s : about 3 t imes i n t h e r a d i a l d i r e c t i o n (from 9,43 t o 2,88 m a ) , i n c i r c u m f e r e n t i a l d i r e c t i o n 1,5 t imes (from 9,43 t o 6,44 MPa). The d u r a b i l i t y o f PCB a f t e r i t s f u n c t i o n i n g i s 3 t imes h i g h e r i n c i r c u m f e r e n t i a l thnn i n r a d i a l d i r e c t i o n . A f t e r 36 months f u n c t i o n i n g PB t i s s u e s u l t i m a t e s t r e s s d e c r e a s e s 2 t imes i n t h e c i r c u m f e r e n t i a l d i r e c t i o n (from 4,136 F I B ) ; i n t h e same t ime u l t i m a t e s t r a i n i n c r e a s e s (from 13 t o 22%). Bi r u t a Pur inya , Vladimlr Yasyanov, Vel ta O s e , L a i l a Feldmane, Guna T e t e r e Riga Po ly techn ic I n s t . , Riga Medicel I n s t .

A f t e r 68 months f u n c t i o n i n g t h e PCB be-

Arti3cial Organs, Vol. 13, No. 4, 1989


297 S . EPIDERMIDIS BIOFILMS: RAPID ASSAY OF ANTIMICROBIAL SENSITIVITY.

Bacterial biofilms may be responsible for the failure of conventional therapy of medical device-associated infection. Current techniques of study are limited by cost, complexity and error. A new technique was developed to determine the viability of intact bacterial biofilms using a metabolic indicator. Standardized S . epidermidis biofilm preparations were formed on various prosthetic surfaces. Following exposure to antibiotics, residual activity of the biofilms was determined by a recovery indicator medium incorporating 2,;,5-triphenyltetrazolium chloride. A readily visible precipitate and colour change indicated intact bacterial function. An absence indicated death. This rapid method allowed large scale screening of antimicrobial activity with detailed examination of concentration, exposure time and potential f o r synergy. This inexpensive, simple and accurate technique determines the anti- bacterial sensitivity of intact bacterial biofilms, leading to optimal therapeutic choices.

Geoffrey Richards, John Prentis, Gregory Obst, Raymonde Gagnon. Montreal General Hospital, McGill University. Montreal, Canada.

298 MODIFICATION OF THE BLOOD COMPATIBILITY OF FLEMODIALYSIS MplBRANES

Suitable approaches for improving the blood compatibility of hemodialysis membranes include chemical modification of the membrane structure and the selection of an appropriate antithrombotic agent. Examples of these approaches have been examined in an in vitro comparison of Cuprophan regenerated cellulose with Hemophan modified cellulose (Akzo, Enka AG) and heparin with hirudin (Ciba-Geigy Pharmaceuticals). The influence on blood compatibility was assessed by measurement of the concentration of the platelet- specific protein beta thromboglobulin (BTG) and that of the complement component C3a. Typical results obtained after 9 min blood-membrane contact were as follows :

Membrane Anticoamlant BTG(nc/mlL CSa(ndml1

Cuprophan none 117 1426 Hemophan none 51 696 Cuprophan heparin 45 613 Cuprophan hi rudin 34 695 The results demonstrate that membrane blood compatibility is influenced by suitable chemical modification or anticoagulant selection and the investigation confirms the importance of considering the options of altering membrane structure or antithrombotic agent for the improvement of membrane blood compatibility.

Lesley M. Robertson, James M. Courtney, %oengingeiing fhit,Univ.of Strathclyde ,Glasgow UK Univ.Dept.of Med. Royal Infirmary, Glasgow U.K.

ordon D 0 Low

5 e u e - a : 5t:ategies tare beer ~rop?sed t: ir:-ease :i e'ci: ienc, i - c-der tc refidre i i a ; j s i s :rea!@ei: t i m F d i - e c

coubinin? tbe advrntagss of highly pertieable nenb-anej ani cc:.vective :-ansport *:t i the higt , de+ratire eff.;acy of diff,ls:os. ?e s r s h operates e i t h twi u:i;ts i r series !iierofi;ter + Dla:y:er' . i ? h meabranes iif polysu;phoq and heaophan respecti . /ely. 4 :erai:e? anaiysie o r :be hydraulic properties o f the system a n 6 its possible optir::aticw i, terms 0 6 depurrtive effic:en:f is 17 this paper. i n vi!:i. a?d is v i v o t e s t s provided data suffi:ient t c drak some bypothesir u ( neb utiiization o f the sycter. The sys ter appear; tc be adequate f o ' npera t i rq under conditluns o f h i g h biooo flour. however some : ieitations appeared evident durir,g our evaluation: The ccnrective coup&sent nay be insufficient and further increases are i8po;sible b e c a m of the Iiniting Effect of the lam sLrface area of the hofi;ter: the configuratior. in nhic'l the neigh! loss is achieved ir

emuf;;ter exposes t o the r isk of backfiltratia.: i n the dialy:er : € a x i n g the benefits of a hiqL;I: biocoapatibie syster; The use G! acetate in the diaiysate andlor the iactate in the substitution fluid aaf interfere dith a satisfactory correction of netaboiic acidosis. 00 the basis of our evaliiaticns, some changes could be proposed ;bch a 5 :: increased surface area of the hewfilter, 21 Use of blood flows higher than 120 #!inin; 3: use of bicarbonate in the dialysate and in the replacerent solutien; 4)Increased convective component nith ultrafiltration rates o f W b 0 mlliin and full replacement u:th Substitution fluid in betreen the two filters; 5: w i g h t loss achieved i., the dialyzer with a constantly positive transmembrane pressure. YiLbh such a modification o f the operative conditions, PFD can be probably applied as a highly efficient dialysis technique i n a large number of patients with a significant reduction o f dialysis treatlent time.

I . . . ,iLrat:jr dialysis ( i d 0 ChlnPEP :ECiiliiQUi; is d x,, t e c h i ; u f

i epor ted

C.Ronco, M.Feriani, S.Chiaramonte, A.Brendolan, P.Conz, 6. La Greca. Department. o f Nephmnlogf, StgOrtoln Hpspital, Vicenza, I t a l y -

The optimization of artificial liver support systems intended for application in the treatment of acute fulminant hepatic failure would benefit from an increased knowledge of the circulating toxic metabolites present in hepatic coma. For this purpose a novel liver failure model has been established in the rat by utilizing extracorporeal circuits for membrane plasma separation and plasma exchange. A technique of reverse plasma exchange has been used to achieve the transfer o f hepatic coma from galactosamine- treated comatose donors to normal recipients. This liver failure model is reproducible in the different grades of coma, with the grade of coma induced in the recipient corresponding to that of the donor plasma. The data acquired demonstrate a direct relationship between circulating toxic metabolites and the development of hepatic coma. Subjection of donor coma plasma to treatment with selected membranes o r sorbents prior to transfer to normal recipient animals enables information to be derived on the nature of solutes implicated in hepatic coma and the effectiveness of artificial liver support systems. This information facilitates artificial liver support design and preclinical evaluation.

Calvin J. Byan, Mohanmed Adam, James M.Courtneq Dept. of Surgery, heremith Hospital, London.UK Bioengineering Unit, University of Strathclyde, Glasgow, m.

Artifkial Organs, Vol. 13, No. 4, 1989


301 STUDY OF BIOPROSTHETIC VALVE FAILURE: MODALITY AND COUNTERMEASURE

Thirty re-replacements (re-R) of bioprostheses (BP) in 27 patients (pts) were studied. Problems of valve ( V ) failure and countermeasure to this affair are discussed. Numbers of implanted V at the initial and re-R were listed as follows.

Mitral 27 (7) 6L (18) 6 97 ( 2 5 ) Tricuspid 0 1 ( 1 ) 0 1 ( 1 )

Total 30 (7 ) 82 (23) 6 118 (30) H:Hancock porcine xenograft, CE:Carpentier- Edwards porcine xenograft, 1S:Ionescu-Shiley pericardial V, ( ):Numbers of re-R V

Male/female was 16/11 with a mean of 42.3 yrs (24-65 yrs) at re-R. The duration until re-R was 92L22.5 months (rnon), ranging 35 to 133 mon. Deterioration of BP was found in 2 5 pts and BP endocarditis in two. Urgent re-R after 35 mon was performed only in one case with cusp tear and life threatening mitral regurgitation. Six pts died of at re-R ( 2 2 % ) and two of late cardiac- related cause. Eighteen out of 26 explanted Vs more than 6 yrs of implantation had calcified cusp. Sixteen out of 26 had tear on the cusp. The actuarial survival rate of re-R series at one and five yrs was 76, and 63%, respectively. The pts with BP over 6 yrs should be managed with thorough knowledge of structural valve deterioration of BP.

Hideaki Saigenji, Kazuhiro Arikawa, Yasuo Morishita, Akira Taira 2nd Department of Surgery, Faculty of Medicine, Kagoshima [Jniversity, Kagoshima, Japan

303 DEvEulpMpHT OF AN IMPLANTABLE MUSCLE POWERED CARDIAC ASSIST DEVICE(HCAD).

The proposed MCAD addresses current problems of existing systems; namely thromboembolism, relatively low power efficiency, and vascular delay. This valveless device consists of a collapsible dome mounted on the back of a biolized pusher plate pump(stroke volume=60ml) with saline as the hydraulic coupling between the two compartments. The assembly is positioned under the in-situ latissimus dorsi muscle and crisscrossing ports are anastomosed serially to the descending thoracic aorta. Features include a high efficiency dome with large surface area, spring enhanced filling and the option of pneumatic actuation via a standard IABP console. Ex-vivo static power studies on 6 dogs(20-30Kg) resulted in a maximum specific power output of 7.81 watts/Kg at physiological afterloads, with stroke volumes of 61.71111 able to be ejected in an average of 53Omsec. In acute implantation using the unconditioned muscle of a goat (53Kg), 1:l CP resulted in pump off to on increases in diastolic augmentation by 16% and decreases in end diastolic aortic pressure by 8%. Stimulation parameters were; 5mA amplitude, 45Hz frequency, and 3msec pulse width. In addition, the endocardia1 viability ratio showed an off to on increase of 1827%. Using the IABP console, this value was dramatically raised to 117+36%.

From these studies, this MCAD design demonstrates promise not only as a CP but also as a possible right ventricular assist device. Naoki Sakakibara, Roberto Novoa, Charles Davies, Ji-Feng Chen, Gordon Jacobs, Dale Mitchell, i’ukihiko Nose and Floyd Loop, The Cleveland Clinic Foundation, Cleveland, OH, USA.

302 NOVEL Bz-MICROGLOBULIN AS P. PPSCURSOR PROTEIN OF DIALYSIS-RELATED AMYLOIDOSIS AND ITS REMOVAL

We earlier reported the existence of a novel On-miCrGglGbUlin(5,-MG) other than an intact f 3 z - ~ ~ in the plasma of hemodialysis patients. In the present study we investigated its accumulation in the blood and deposltion to tissue, along with its removal with high-flux dialyzers.

50 i l l serum from 10 normal subjects, 15 undialyzed uremic patients and 30 dialyzed patients, and Bz-MG detection was performed by immunoblotting technique. B2-MG analysis was then performed using extracts from transcarpal ligaments. Hemo- diafiltration was performed on another 10 dialysis patients using Fresenius F-60, Terumo CL-SS-12 W and BK 2 . 0 P(PMMA) dialyzers, respectively. The same analysis was undertaken with the serum and the ultrafiltrate.

The novel B2-MG could not be detected in the normal serum, but was found in that of 3 of the 15 undialyzed uremic patients. It was detected in all 15 patients who had been on dialysis for less than 5 years. And the concentration was hing in those with more than 10 years on dialysis. In the sample extracted from tissue, there was mainly the novel Bz-MG. Analysis of the ultrafiltrate revealed no novel B2-MG in the sample obtained with PMMA, and 2-3 spots of novel 52-MG were found with the other dialyzers. Equivalent adsorption of native and novel Bz-MG was recognized with the use of the RMMA dialyzer, while with other dialyzers the removal rate was the same as with native B2-MG. Jkira Saito, Hiroshi Ogawa and Masataka Ono The Bio-Dynamics Research Institute, Nagoya, Japan

Two-dimensional electrophoresis was applied to

304 A NEW NONINVASIVE REFLFXTIVE PULSE OxlwKTER AS A FUTURISTIC SYSTEM FOR ARTIFICIAL HEART CONTROL

Current transmissive pulse oximeters (TPO) can yield rapid and noninvasive measurements of arterial hemoglobin oxygen saturation(Sa0 ). However, their applications are limited to $he finger-tip or ear-lobe. For these locations, it is often difficult to obtain stable data in pediatric cases. The newly proposed reflective pulse oximeter (RPO) has the potential of being applicable to any skin surface of the body or even internal organ surface if implantable. In addition t o Sa02, local venous saturation(Sv0 )

The RPO showed a better correlation (N=93; Y= 0.93X+6.0; r=0.983) with IL282 CO-Oximeter(1n- strwnent. Lab.) than the TPO (N=93; Y=0.65X+33.8

2 ; r=0.919) in the range from 40% to 100% of SaO with 4 dogs. Also, the RPO was applied to forehead, cheek or arm in clinical patients (N=3) undergoing surgery or treated in ICU. In comparison to the TPO, the RPO responded more rapidly to changes in the respiratory status.

From these studies, the RPO can be applicable for not only noninvasive monitoring of SaO from the skin surface of critical patients, but! also evaluating the adequacy of oxygen delivery to particular target organs. When the Sa02 information is combined with central and/or local Sv02 information, the proposed RPO has a potential application in control of a completely implantable total artificial heart output.

Naoki Sakakibara, Setsuo Takatani. Charles Davies, Hiroyuki Iris, Dale Mitchell, Yukihiko Nose, The Cleveland Clinic Foundation, Cleveland, OH, USA.

and blood volume may be obtained noninvasively. 2

ArtiJicial Organs, Vol. IS. No. 4, 1989


7 6

f3

359

I5 ARFu (0 3 6 I f5 43 40 I 41 8 a 12 L CRFB 4 4 ' 1 1 4 3 [ I 3 1 4 1

17 130 t z 7 j o i 49 16 4f 1 45 f4 9 43

305 FERRCCENE-MEDIATED GLUCOSE SENSOR FOR SUBCUTANEOUS TISSUE GLUCOSE SENSING

Since standard glucose sensor consumes oxygen in enzymatic reaction, low oxygen tension in sensor-inserted subcutaneous tissue affects sensor output. Thus. the development of glucose sensor that does not require oxygen m y be advantageous.

An enzyme electrode incorporating glucose oxidase (GOD) and ferrocene as a mediator of electron transfer has been developed, and the characteristics of this sensor in vitro were examined.

Ferrocene carboaldehyde was deposited in the space between the electrode and C4D membrane, and steady state current was measured at + 0.4 volts. 1. As compared to the standard glucose sensor, oxygen tension did not show any significant effect on the output current, even in the zero oxygen condition. 2. Even in the low oxygen tension, a linear current, proportional to glucose concentrations was observed. 3 . D-mannose and galactose interfered s l i g h t l y with the sensor current, but other reduclng substances such as ascorbic acid, uric acid and so on, did not show any observable interferences. 4. The feasible molar ratio of ferrocene to GOD was demonstrated to be 30 to 1.

It was concluded that the ferrocene-mediated glucose sensor showed minimal sensitivity t o relevant oxygen concentrations, and might be applied to clinical hypoxic condition observed in case of diabetic coma. The ferroeene -mediated glucose sensor in a form of needle type f o r subcutaneous sensing i s under development.

~.sakakida, K.Ichinose, H.Fukushima, S.Tomimura*, 1.Taniguchi* and M.shichiri, Dept. of Metabolic Medicine, Medical School and hPt- of @Plied Chemistry, Kumamoto Univesity. Kumamoto 860, Japan

The depression of the blood pressure or shock are mainly attributd to t h e blood volume and hemoglobin oxidization during the hemopurifiction treatment,, esspecially short time treatment.

To realize a safety and a more organismjcai iir-ti ficial kidney ss-stem, a new hemopurification c-ontrol system has been developed as a cybernics system composed by a blood pressure regulation system as a central nervous system or homeost.asis, circul at.ory model, body f 1 uid model, internal body state observer as a cognition s)-strin which includes patient. model above, raser hemat.n- and oximeters as sensory receptors of h3 nod solume and hemoglobin osidization, blood p res su re sensors, and optimal control program niinimizjng a performasnce index.

The pressure regulation model has a volume receptor and a pressure receptor which detert the right atrial pressure and the arterial pressure rpnpect i\-ely. Here, heart r a t i o , cardiac tension and vessel resistance are varied to regulate t.he hlood pressure with the gain parameters of these receptors. The body fluid model adopted here c2onsist.s of three compart>ment.s; blood, ISF, ICF. By utilizing the above models, an optimal program is gotten to minimize the blood pressure decrement under the given dailysis criteria of total watar removal as well as the rmste product removal and total treatment time.

Totards t.he safe and short-time treatment, an integrated patient.-artificial kidney system has '=en developed based on a cybernics conception to keep the blood pressure in the safety range in reasonably shortend treatment.

Yoshiyuki Sankai. Michio Ohta, Yoriaki Kumagai Inst. of Engineering Mechanics, University of T s u k u b a , Ibaraki, Japan , Keihin Hospital, Tokyo, Japan

306 pH-DEPENDENT AMMONIA CLEARANCE DURING BICARBONATE HEMODIALYSIS

stage renal disease. To examine the effect of dialytic therapy on this nitrogenous molecule, we determined in eight subjects with acute renal failure the clearance of ammonia by a cellulose acetate dialyzer using a standard bicarbonate bath (pH 7.44, blood flow 200 mllmin, and dialysate flow 500 ml/min). Ammonia was measured in blood obtained from the arterial and venous sides of the dialyzer within 15 min of the initiation of dialysis. Ammonia decreased significantly across the dialyzer from 60216 to 43?14 pmolelL (p<O.Ol) with a mean decline of 1723 pmole/L. Ammonia clearance showed wide interindividual variation ranging from 27 to 100 mllmin with a mean of 68.2 ml/min, a large coefficient of variation ( 3 5 . 2 % ) and was significantly lower than urea clearance (176 ml/min) despite the smaller molecular weight of ammonia (17.03 vs 60 .06 ) . To explore the mechanism underlying this variability, we examined correlations of ammonia clearance with biochemical and clinical parameters. A highly significant positive correlation was observed between ammonia clearance and predialysis plasma bicarbonate (r=0.912, p<O.OOl). These results suggest that the clearance of ammonia is pH-dependent because of the predilection of the molecule to be more soluble in acidic media. As arterial pH increases during dialysis, and blood-dialysate pH gradient narrows, ammonia clearance may rise and become pH independent. Mohammed Salem, Peter Ivanovich and Salim Mujais. VA Lakeside Medical Center and Northwestern University, Chicago, IL, USA

Hyperammonemia is a common occurrence in end-

CLINICAL EXPWIWCE WITB CONTIWOWS BILX)FILTBATION I B F I IN 308 BRAZIL- SERVICO DE NEFROLOGIA.HOSPITAL DO ANDARAI AND

CLINICA MEDICA II1,ESCOLA DE MEDICINA E CIRURGXA. UNI-RIO. RIO DE JANEIRO, BRASIL.

Continuous HF has been used for treatment of renal failure with hnervolemia/hemodynamic rnstability. Pre or post-filter fluid reposition or slow continuous ultrafiltration (SCUF=Jml/minl are employed. HF can be also used as CAVH only or associated with dialysis (CAVHD).

SCUF was started in 13, CAVH in 13 and CAVHD in 4 pts. fn=30) with 8 complicated C R F 1sepsis.refratary edema,CHF) and 22 severe AFiF I8 surgical.9 medical.5 obstetric); 29 adults ( 9 over 8 5 ~ ) with mean age 47.4~. Early utilization (mean pre ScreaG5.72 ~ 2 % ) ln view of expected hyper- catabolic or prolonged course was tempted.AV fernural 11.5 cm poliuretane Vygon cath.(21). double-lumen cath.(S), Scribner shunt ( 2 ) and AV fistula (1) accesses were used. Continuous heparinization with infusion pump 1500-1500 U/h) was glven to most pts. and pre-dilutional (CAVH/D) reposition with Ringer-lactate was preferred. Amicon 20 ( 2 8 ) or 30 ( 2 ) polvsulphon o r Biospal ( 5 ) filters were used (whole mean filter duration=39,8h) over 469 SCUF and 925 CAVH/D hours procedures I5 to 177 h; 66.6Xk24h and 36.6%L60h). Decrease of Screat (mean post=3.?6 ma%) was achieved among all survivors without concomitant dialysis. Complications included filter coagulation 110x). hematoma Ilx), pericath. bleeding llx). hypotension 14x) and GI bleeding ( 2 ) . Mean fluid remotion was 180.9 nllh (SCUFjand 414 mllh (CAW/D) I206 to 771 ml/b).

organ failure. lung embolism, rniooardial infarction and AV heart block, as well as 118 CRF pts.lheart tamponade); 3 CFlF pts got back to clinical control and 4 started chronic di a1 ys is. * In spite of the high morbidity.the results were favourable in 56.6%; 8 HF procedures are simple, safe, effective and not expensive methads able to give continuous support of renal function providing hemdynamic normalization, easy fluid control and adequate nutritional and caloric intake.

R.FIRNANDES. .J. MAOALHRES Ft, K.P. QUEIROZ ~ I B A . H. MIA SEEPA, Ar *IILLER FERBMIX. BUTHDRS- 0 . DA I~DSA WTOS,P. COSTA I SILVA. n. HEYW

Art$cial Organs, Vol. 13. No. 4, 1989


309 CLINICAL EXPERIENCE WIT8 KEmPERFUSlON LBp\ FOR EXffiENOOS INTOXICATIONS IN BRAZIL- SERVICG DE NEFROLOGiA DO ROSFITAL DO ANDARAI. RIO DE JANEIW), BRAS15

HP i s e f f e c t i v e f o r d rug removal . Wr performed 2 2 HF s e s s i o n s i n 1 6 p t s . !age 16-63 Y . 9 m and 7 fm) wi th exogenous i n t o x i c a t i o n s due t o v o l u n t a r y i n g e s t i o n o f drug ove rdoses , i s o l a t e d or i n s e v e r a l comt , ina t l sns . b a r h i t u r e t r s (9;. benzodiaZe€, ines ( 6 1 . h a l o p e r i d o l 1 3 1 , ~ r o m r t a z i r ~ e ( 2 ! , a lcoho l ( Z ) , an .Yt r ip t i l i oe ( 2 1 , d i 6 o x l n , d i p i r l d e m o l e . c lo rp romas ine . methi l -doph, e ru th romyr in . pa raqua t and organophosphate 11 each!

HP use w a s j u s t i f i e d i n c l i n i c a l g rounds : r e s p i r a t o r y i n s u f f i c i e n c y ( loo%! , deep coma 1100% > , hemudynamic i n s t a b i l i t y ( 3 7 . 5 % ) . I t w a s s t a r t e d f r o 5 4 h t o 6 days a f t e r d r u c i n g e s t i o n . Vascu la r a c c e s s e s were t h rough s i n g l e lumen venous c a t h s . . h i f emura l ! 7 ) , f e m u r a l - s u t c l a v i a n l 7 ; , f emura l - jugu la r ( 2 ) . HP was done wi th blood p a s s u e over a c t i v a t e d c h a r c o a l LAdsorLa 300) and r epea ted once i n 2 and twice i n o t h e r 2 . ARF was p r e s e n t i n j u s t 1 p t . Ipa r squa t ! . t o g e t h e r with s e v e r e lung and l i v e r l e s i o n s :dea th cadsed h s pulmonary embolism) : a s s o c i a t e d henlodialysis was emplo?ed in t h i s p t . and i n one o the r lmegados i s of f l u n l t r a z e p a n - 6 4 0 ml) vhc, a lac , r ece ived a hcnzod iesep ine a n t a g o n i s t infuslorr a t t h e venods e r r t r y ( t h i s c b r e d ) . Complete r ecove ry *.as piomptly achieved i n 14 p t s ( o n e d i e d a week l a t e r d u e t o lung La ro t r aumai . The o t h e r d e a t h occur red with a pt. a d a l t t e d t o o l a te ( 6 days a f t e r the i n t o x i c a t i o n ) w:th severE pr iemonia. Thus lurig involvement W ~ S the c t . i e i d e i e r m i n a t o f t h e m c r t a l i t y . Compiicat . ioas i n c l u d e p u h o n a r y embslism ( 1 ) , hematorna ! 2 ) , moderate anenli M : 2 ) m d t h r o m b o c i t u p e r ~ i a 1 1 ; * HF is illl ex t r eme ly v h l ~ a b l e t h e r a F r t m 1 i u seveTe e x o ~ a n o u s i n t o x i c a t i o n s ; i t 1 s at:e t o recover yts :tt,erw?se odt of t h e r e p e u t : ~ p o s s i b i : ; t i e s . siiorCs3ing t h e f lmt uf unconsc iousness end r educ ing t h e ? n f e o t i o n a

Ir. t k i s s e r i e s i t was e f f e c t i v e i n 8 7 . 5 % * M o r t a l i t y was d u e e x c l u s i v e l y due tn ;iiln~-Tihry reasu!.s w. 0. DA ROSA SANTOS, J . 3 . M A G . a A . S I L V A ANDRADE H. Y. 1BRAHIM.C.E.BETEILLF.M BRAUN, M. DA P E N U DE SOUZA. SILVIA Q PEREIRA

311 A NEW THERAPY FOR GASTR C ULCER - N V I V O STUDIES-

G a s t r i c u l c e r s i n rats were t r e a t e d wi th o u r newly devised m a t e r i a l , " G . T . X I I 1 " . The G . T . X I I 1 w a s p repared by l y o p h i l i z i n g thrombin(T) and b lood c o a g u l a t i o n f a c t o r X I I I ( X I I I ) , t o g e t h e r wi th b i o - degradable g e l a t i n powder((;). Such prepared mate- r i a l w a s e a s i l y changed i n t o i n j e c t a b l e s o l form.

s u b s e r o s a l i n j e c t i o n of a c e t i c a c i d s o l u t i o n t o normal and diabetic(DM) r a t s , which were induced wi th S t r e p t o z o t o c i n . A f t e r 3 d a y s , t h e a l l r a t s were gas t ro tomied t o confirm u l c e r format ion . Then G . T . X I I I s o l w a s d i r e c t l y i n j e c t e d t o t h e u l c e r s ( t r e a t e d group,30 r a t s ) . G . T . X I I I w a s n o t g iven t o the c o n t r o l s ( 2 8 r a t s ) . The h e a l i n g process of the u l c e r s was macroscopica l ly and h i s t o l o g i c a l l y observed f o r 4 weeks. The grade of h e a l i n g was e v a l - u a t e d accord ing t o endoscopic c r i t e r i a of u l c e r s t a g e ; namely, a c t i v e s t a g e ( A ) , h e a l i n g s tage(H) and s c a r r i n g s t a g e ( S ) .

A punched-out u l c e r was formed i n every r a t . A l l t h e t r e a t e d an imals s u r v i v e d , b u t 5 rats i n t h e c o n t r o l s d i e d of p e r f o r a t i o n of t h e u l c e r i n 7 days. Macroscopica l ly , t h e t r e a t e d u l c e r s showed wel l -organized h e a l i n g p r o c e s s i n a s h o r t term. While, r e p a i r i n t h e c o n t r o l s w a s remarkably poor . I n DM r a t s , t h e u l c e r h e a l i n g was a l s o s u p e r i o r i n t h e t r e a t e d group. A l l h i s t o l o g i c a l s t u d i e s sup- p o r t e d t h e s e g r o s s f i n d i n g s .

These d a t a s u g g e s t t h a t t o p i c a l i n j e c t i o n of G . T . X I I 1 promotes u l c e r h e a l i n g and c l i n i c a l a p p l i - c a t i o n of t h e m a t e r i a l i s expec ted .

E.SATOH, Y.SASAYAMA, A.YAMAMOTO,'M.MDR&I, M-MASU- ZAWA, K.TAMURA and A.SUGITACH1. Osaka N a t i o n a l H o s p i t a l , Osaka 5 4 0 , Japan.

In t h i s s t u d y , g a s t r i c u l c e r s were induced w i t h

310 IMMEDIATE SCORING MEIYIOD TO SELeCp A SUITABLE MECHANICAL SCTPPORT FOR PATIENTS WITH PROFOUND FJEIwr FAILoRe

To define IABP patients who need more potent drculatory support, such a s a left ventricular assist device (LVAD), an objective and synthetic p r o g n o s t i c s c o r i n g method was d e v i s e d by analyring clinical data using a Statistic method.

W e reviewed 129 IABP patients between 1982 and 1987 to establish a scoring method by comparing s u r v i v o r s with non-survivors by means of a multivariant discr iminant analysis . Using t h i s method, prognosis of 22 IABP patients in 1388 were evaluated.

Based on the values of Six parameters selected o u t with s ignif icant differences; mean aor t ic , central venous and left atrial pressure 4 hours a f t e r t h e IABP appl icauon, extra-corporeal d r c u l a ~ n t i m e , presence of organ failure, and reasons uf indication, graded and weighted these parameters, w e established an easy and objective scoring method as a r i s k score. T h e full m a r k s of the r i s k score is 48. A l l IABP patients wi th the r i s k score < 15 surv ived; 1 7 percent of t h e pa t ien ts with t h e r i s k score < 20 died and 95 percent of the patients w i t h the r i s k score 2 20 died. Only one of 22 patients in 1988, bounded on 20 marks, was unexpected w i t h the risk score.

O u r method was easily appl icable , and the prognosis of patients was predicted precisely 4 hours after t h e IABP application by the method. The IABP patients w i t h rhe r i s k score 2 20 wi l l n o t s u r v i v e a n d a r e c a n d i d a t e f o r a more effective support such as LVAD. E. Sasaki, H . Takano, Y . Taenaka, H . Noda, M . Kinoshita, E. Tatsilmi, H . Sekii, A . Yagura, T. Fuj i ta , T. Akutsu, H . Manabe Natmnal Cardiovascular Center, O:;aka, Japan

312 LYMPHOCYTE-APHERESIS USING THORACIC DUCT DRAINAGE

Lymphocyte-apheresis u s i n g t h o r a c i c d u c t drainage(TDD) has been recognized as an e f f e c t i v e t r e a t m e n t f o r v a r i o u s autoimmune d i s e a s e s such as c h r o n i c rheumatoid a r t h r i t i s ( R A ) b u t has n o t been g e n e r a l l y accepted due t o t e c h n i c a l and o t h e r problems such as hypoproteinemia from massive removal o f lymph and t h e r e s t r i c t i o n of s o c i a l l i f e by t h e e x i s t e n c e of a d r a i n a g e l i n e . To s o l v e t h e s e problems, we have developed a new on- l ine system of lymphcyte-apheresis u s i n g a new f i l t e r s u p p l i e d by Agishi e t a l . e n a b l i n g e a s i e r and more e f f e c t i v e lymphocyte removal. Also, we r e p o r t our new technique of long-term TDD f o r o u t p a t i e n t s i n v o l v i n g a s p e c i a l l y - implanted subcutaneous v a s c u l a r a c c e s s device . :J$ have a p p l i e d TDD f o r 4 p a t i e n t s , w i t h d e f i n i t e o r c l a s s i c a l RA and performed s e s s i o n s over 10 t o 14 weeks. A f t e r t h e d r a i n a g e had been s t a r t e d , t h e average volume of lymph was 4600ml/day t h a t enabled u s t o remove 2.0 x 10 /1000ml of lymphocyte (mean s p e c i f i c i t y removsl rate; 96.4%). The r e s u l t s which we obta ined were s i g n i f i c a n t i n d e c r e a s i n g t h e T /T r a t i o i n a l l c a s e s and f o r 3 of 4 p a t i e n t s ifi %ecreased RAHA. S i g n i f i c a n t improvements i n t h e Lansbury Index , a t more than 30%. We assume t h a t t h e o b t a i n e d c l i n i c a l improvements depended on t h e immunosuppression by d e c r e a s i n g h e l p e r T-ce l l . Lymphocyte-apheresis u s i n g TDD i s e f f e c t i v e for chronic RA and we recommend om new t e c h n i q u e s f o r t h i s and o t h e r autoimmune d i s e a s e s . Takashi S a t o , Nobuhiko Koga, Taketoshi Nagano, H i t o s h i Ohteki , Te tsuzo A g i s h i , Toshiak i Masuda Koga H o s p i t a l , Dept. of Thorac ic & Cardiovascular Surgery , Saga Medical School , Nipuro Co.,

FOR PATIENTS W I T H CHRONIC RHEUMATOID ARTHRITIS



313

315

A MULTIPLE ENZYME SYSTEM FOR DETOXIFICATION OF TOXIN MIXTURES WITH LIPOPHILIC HOLLOW-FIBER MEMBRANES The principle of transmembranous enzymatic detoxification has been investigated with single toxins and their corresponding enzymes. For practical application it is of importance to know whether this principle can be applied f o r toxin mixtures and a mixture of the corresponding enzymes. Transmembranous enzymatic detoxification of p-cresol, dodecanoic acid, p-NBC by single enzyme preparations (solubilized UDP-glucuronyl- transferase, liver microsomes and cytosol) in a lipophilic hollow-fiber device were measured to be 2.3, 3.7, and 27.6 nmol/h/mg protein/cm2 membrane surface respectively. With the multiple enzyme system of the three enzyme preparations the values were 2.8, 4.5,and 32.5 nmol/h/mg/ protein/cmz membrane surface, for p-cresol dodecanoic acid, and p-NBC, respectively. These results indicate that different toxins in a mixture do not interfere with their membrane permeation and that their transmembranous detoxification of an individual toxin is not interfered by the presence of other toxins as <ell as other enzymes and cofactors. Therefore this principle can be applicable for enzymatic extracorporeal detoxification of endogenous toxins in liver failure using the lipophilic hollow-fiber technique.

M. Sawa, D. Tsikas, G. Brunner Dep. Gastroenterology and Hepatology Medizinische Hochschule Hannover

114-VITRO-TESTS AIW I w I C 4 L STUDIES OF DIFFERENT IMPELLER DESIGNS FOR CENTRIFUGAL BLOOD

PUEPS The design of impeller rotors with minimal blood traumatization was investigated for use in an implantable centrifugal blood pump. Two types of impeller rotors with a diameter of 5 h were compared in an in-vitro set-up with bovine blood and in numerical simulation. Type IKS had straight radial vanes, type IRF had curved vanes designed according to hydrodynamic theory. The rotors were fabricated out of PVC and tested in an acrylic housing. Hematologic tests were performed with bovine blood under physiological conditions. The pumps were tested over 3 hours at a flow-rate of 5l/min a t 1SonrmHg and compared with a Biomedicus BIO-Pump. A t least 3 experiments were done with each pump. Initial values of (fHb/Hb)~'~1000 were below 0.3. After 3 hours of pumping the indices were 0.74 (+-0.86) for the Biomedicus, 0.4 (+-0.26) for the IRS and Numerical simulation of shear stress was done by finite element analysis. It revealed, that although the maximum of local shear stress on the vanes was far higher for the IRS than for the IRF, the product of shear stress and passage tine was approximately 4 times higher for the IRF. The results prove a direct relation of exposure time and amout of blood traumatizaton. They snowed possible improvements of impeller blood pumps and the necessity of detailed numerical analysis. HL Schima, D. Papantonis +), A. Wohlfahrt, G. Wieselthaler, D. Croba +>, M.R. Miiller, H. Thoma 2nd Dept of Surgery, Univ. of Vienna, Austria; +) Dept. of mech Eng., T. Univ of Athens, Greece

1.27 (+-0.7) for the IW.

314 IMPROVED BLOOD COMPATIBIL ITY BY CVD a -S iC:H COAT I NG

As a l o g i c consequence i n t h e unders tand ing of phys ico -chemica l processes i n t h e i n t e r f a c e o f b i o m a t e r i a l s and b lood , t h e s u r f a c e s t r u c t u r e r e - s p e c t i v e l y t h e s u r f a c e p r e p a r a t i o n p l a y s an impor- t a n t r o l e i n t h e improvement o f c a r d i o v a s c u l a r i m - p l a n t s . As p y r o l y t i c carbon c o a t i n g r e p r e s e n t s t o - d a y ' s s t a t e o f t h e a r t t h e hemostas is i s s t i l l a f - f e c t e d by d isadvantages o f t h e e l e c t r o n i c s t r u c - t u r e o f t h o s e m a t e r i a l s . Comparat ive studies w i t h o t h e r m a t e r i a l s have shown improvements i n hemo- c o m p a t i b i l i t y as a r e s u l t of a b e t t e r ma tch ing o f t h e e l e c t r o n i c parameters such as e l e c t r o n concen- t r a t i o n , band gap energy and s u r f a c e s t a t e d e n s i - t i e s . Based on an e l e c t r o c h e m i c a l model c o n s i d e r - i n g t h e a c t i v a t i o n s o f f i b r i n o g e n as an redox p r o - cess i n t h e s o l i d b l o o d i n t e r f a c e T i O 2 , TiN, S i N and S i c have been e x p e r i m e n t a l l y eva lua ted . These m a t e r i a l s a re depos i ted as amorphous doped semi - c o n d u c t i n g 1 ayers by r e a c t i v e s p u t t e r i n g and chem- i c a l vapor d e p o s i t i o n ( C U D ) , e s p e c i a l l y doped S i c has proven t o be b l o o d - c o m p a t i b l e s u p e r i o r t han t h o s e o f p y r o l y t i c carbon p r o v i d i j y an e l e c t r o n c o n c e n t r a t i o n o f app rox ima te l y 10 cm-' w i t h a band gap energy of approx ima te l y 2 eV. The r e s u l t s have demonstrated t h e f e a s i b i l i t y p roduc ing an ap- p r o p r i a t e e l e c t r o n i c s t r u c t u r e t o meet blood-com- p a t i b i l i t y requ i remen ts . Plasma a c t i v a t e d C V D o f - f e r s t h e advantage t o match e l e c t r o c h e m i c a l s o l i d s t a t e and mechanica l requ i remen ts i n t h e des ign o f a r t i f i c i a l h e a r t va l ves .

Schaldach, Max Department o f B iomedica l Eng ineer ing , U n i v e r s i t y o f Erlangen-Nuremberg, Er langen, West Germany

316 E v a l u a t i o n o f KAllEKA SYSTER in LDL apheresis

A llew g e n e r a t i o n o f t e c h n i r s c a n be a p p l i e d t o r e m o v e s e l e c t i v e l y s o m e k i n d o f m o lecules. it i s t h e f i e l d o f Plasmatreatment. Among t h e a d a i l a b l e procedures . thc a d s o r p t i o n o f cho!esteroi by r h b m e a n of O e x t r a n s u i f a t e a f f i n i t y is promised c e r t a i n l y t o a n i m p o r t a n t d e v e l o p m e n t . I n t h i s c c o m u i i c a t i o n , ;ie r e p o p t t h e r e s u l t s o f 3 h y p e r c h o l e s t e r o l e m i a p a t i e n t s t r e a t e d w i t h K a n e k a s y s t e m . M a t e r i a l use? : K a n e k a m o n i t o r ( M A O 1 ) t h i s m a c h i n e c a n

rhecked t h e p l a s m a s e p a r a t i o n a n d t h e plasmatreatnent. T h e d i s p o s a b l e is d i v i d e d into t w o parts. l h t p r i m a r y system in which t h e w h o l e b l o o d i s s e p a r a t e d by an h o l l o u f i b e r f i l t e r ( S U L F L U X ) . The s e c o n d a r y s y s t e m is c o m p o s e d w i t h t w o c o l u m n s ( L A 1 5 ) fi!led uith d e v t r a n i u l f a t e (150m1). iiepzrin ( 2 0 0 0 U I p a r l i t e r ) i s u s e d a s a n t i c o a g u l a n t solution

We p e r f o r m e d b e t v e e n one and 4 t r e a t m e n t a p e r month. We h a v e c o p t r o l l e d t h e t e c h n i c a l p l o c c d u r e and t h e e f f i c a c y and h e m o c o n p a t i b i l i t y uf t h e system. The b i o i o g i c a l results s h o w a good efficacy o f t h e c o l o l u m n s ( E x t r a c t i o n r a r e o f L D L c h o l e s t e r o l = 7 0 % ) w i t h 2 good recovery o f H D L Cholesterol. i h e r e i s a g o o d c o n s e r v a t i o n o f the p l a s m a m o l e c u l e s ( P r o t e i n s , I m m u n o g l o b u l i n s , c o a g u l a t i o q factors). T h e h e m o c o n p a t i b i l i r y show 2 g e q e r a t i o n o f a n a p h y l a t o x i n s ( C 3 a ) u h i c h is t r a p p e d by d e x t r a n sulfdte. In c o n c l u s i o n K a n e k a s y s t e m i s a good t e c h n i c to r e m o v e L L L c h o l e s t e r o l w i t h o u t s e r i o u s s i d e effects. N o w u e have t o t e s t c l i n i c a l e f f e c t s o f c h o l e s t e r o l e x t r a c t i o n .

F. SCHOONENAllo - 0. ZIESLER' - F. STREIFFO C e n t r e d e Transfusion S a n g u i n e de Nancy 5 4 5 1 1 VANOOEUVRE F .

S e r v i c e d e Med. G. -Hijpital de T O U L 54 D O M M A R T I N L E S T O U L F .

Art$cial Organs, Vol. 13, No. 4, 1989


317

319

EVALUATION OF HEY PLASMA F ILTRATIOX SYSTEM FOR COLLECTION OF SOURCE PLASHA

Meebrane p l a s m a p h e r e s i s i s u s e d b o t h t h e r a p e u t i c p r o c e d u r e s and f o r c e l i f r e e p lasma c o l l e c t i o n f r o m b l o o d d o n o r s . I n t h i - s t u d y , ue have t e s t e d a p r o t o t y p e membrane f i l t r a t i c n i n s t r u m e n t ( A S A H I ) . - The f e a t u r e s o f t h e s y s t e m a r e a s f o l l o u e d : s i n g l e arm d o u b l e l u m e n n e e d l e a c c e s s , a s u r f a c t a n t f r e e h y d r o p h i l i r e d p o l y e t h y l e n e membrane ( N o l l o w f i l t e r , APT. 200 A S A M I M e d i c a l

- 30 p r o c e d u r e s & e m p e r f o r m e d frum 30 d i r f e r e n t d o n o r s . The p r o c e d u r s a r e c o m p i e t c o n l y i,, 2 4 d o n s r s 1 1 4 g , 1 0 6). - The p h r p o s e ;f t h i s s t u d y i s t o t e s t t h e m o n i t o r end e v a l u a t e t h e q u a l i t y o f c o l l e c t e d p lasma. - R e s o l t s : - Time c o l l e L t i o n (600 m1 of p l a s m a ) = S8.28 T 12,7 mn

L o 1

- B i o l o g i c a l d a t a : F r e e HB = 0.8 T o t a l p r c t e i n s = 54,2 Z G,4 g f l i t e r IgG = 7.55 1 1,6 g / l i t e r p l a t e l e t s = 8 . 5 7111 c = 117,9 4 1 % C3a d e s a r g = > 9000 n q / m l F i b r i n = 2,38 7 0.5 g i l i t e r

0.4 m g / l i t e r

4 , i x l q p ,

- No b a d s i d e e f f e c t s a r e d e s c r i b e d i n t h e d o n o r s . N e v e r t h e r l e s s i n 4 p r o c e d u r e s ue have t o s t o p t h e r u n

( s i n c e t e c h n i c a l p r o b l e m s ) . i n 2 p r o c e d u r e s : The d i s p o s a b l e was d e f a c t e d .

I n c o n c l u s i o n t h i s s y s t e m seems t o be a good a p p r o a c h t o c o l l e c t iell f r e e p l a s m a f rom donors . B u t . u e have u s e d a p r o t o t y p e . A s a h i r e s e a r c h has t o i m p r o v e t h e m o n i t o r t o o b t a i n more s a f e t y p r o c e d u r e , and t h e q u a l i t y a f t h e d i s p o s a b l e . I t r e m a i n s an i m p u r t a n t p r o b l e r : t h e membrane g e n e r a t e s C3a.

F. SCHOONERAN - H.E. BRIQUEL - F. STREIFF

54511 VANOOEUVRE F R A N C E C e n t r e de T r a n s f u s i o n Sangu ine de NANCY

TBE MICROPOROUS TRACBEAL PROSTHESIS

Since complete incorporation of a tracheal prosthesis with an epithelial lining seems to be required to prevent infection and granuloma formation, we developed a polyurethane reinforced microporous tubular graft of 20 ma ID and 8 cm length for implantation in the cervical part of the trachea of a goat. Trachea prosthesis N Infection Granuloma microporous controls 7 5 7 +cuff technique 9 7 4 +peritoneum lining 3 2 3 +artificial mucosa lining 3 2 3 +preimplanted + mesh graft 6 3 6 The results indicate that a cuff technique is needed to reduce anastomotic granuloma formation. The artificial skin as well as vital peritoneum were able to prevent infection to occur in the first 2 weeks, but not thereafter because of loosening of the layers. Preimplanted mesh grafted trachea epithelium did not completely cover the graft within 2 weeks, but showed resistance to infection which will be optimal when f u l l incorporation is achieved. I n conclusion: Microporous material permits complete epithelialization in a non-contaminated area (subcutaneous preimplantation). Prevention of anastomotic granuloma formation requires a non exposure of the anastomosis to the airway (cuff technique). Complete epithelialization is needed to prevent infection of the prosthesis.

K.Sedlarik, E.Lommen, W.Hinrichs, J.Feijen, Ch.Wildevuur. University Hospital Graningen, The Netherlands.

318

320

IMTOVID [~LM) FLCM CHARACERISTICS IN PATIENTS w m SEME HYPER-a-CIPCPROTCINMIA ON FECLlAR TfiEATMNT WITH Tt€ EPA- RININMED EXTRACORPOREAL LCC/fIBRIMCEN PRCIPITATION

In contrast to other selective procedures for extracorporeal LDL-elimjnation such as speciflc jmmunoadsorptjon o r dextran sulfate adsorption, fibrinogen is precipltated to the same extent as LOL by heparin-induced extracorporeal LDL-precj- pitation ( H E L P ) . Both LDL and fibrinogen are not only known to accelerate atherogenesis but also affect rheological parameters such as plasma viscosity (PV), erythrocyte aggregatjon (€A) and erythrocyte filtrability ( C F ) . In 10 adult patients with severe type I1 hyperlipoprotelnemja a single HELP treatment o f 3 litres plasma led t o an acute decrease in the average PV from 1.30 to 1.10 mPas. At the same tjme, an even more marked decrease in the mean EA rate from a pa- thologjcal value of 7.9% to a value of 3.7% (normal range<5%) was obseiwed. In parallel, C f jncreased from 13.5 ml/sec to 15.0 ml/sec; this was accompanied by a decrease in the cholesterol/phospholipld ratio from 0.81 to 0 . 7 7 , probably indicating rapjd changes in the flu~dlty o f red cells. Long-term studies on 5 patients demonstrated a lasting improvement i n hmo- rheological variables.

Peter Schff-lkrrer, Ekkd7ard k l u t z , T h m E i s e n k r , Victor Am&rcrq, Dietrlch %1&1 kpt. o f Clinical Chemistry and kphmlagy, klversity Clinics, Goettirq=n, F.R.G.

CLINICAL EVALUATION OF THE NEW PLASMA COLLECTION SYSTEMS BY THE SPECIAL STUDY GROUPE OF THE JAPANESE RED CROSS SOCIETY

The lately licensed four membrane plasma collection systems(NDP-100 and NDP-200:Nipro Co. Ltd., Japan, APC-2000:Asahi Medical Co. Ltd., Japan, and Autopheresis-C: Baxter, USA) and two centrifugal plasma collectors(PCS and Ultra-light PCS:Haemonetics, USA) were selected and subjected to the clinical tests.

Over a thouthand times of plasma collection procedures were performed on healty voluntary donors, and about 450 ml of plasma was collected at each procedure. In order to evaluate the donors' safety, blood samples of donors and in a circuit were taken and were submitted to the hematological, biological and coagulation tests. The plasma collected were similary characterised. From the views of efficacy, operation time, frequencies of troubles and accessibilities f o r operators were evaluated.

be introduced to the donor plasmapheresis program of the Japanese Red Cross. However, a few but significant modifications were necessary for the apparatuses and/or setting parameters for operation.

In conclusion, all systems evaluated here could

Sada oshi Seki uchi Chlef of Study Group) Sadaiitsu Yama:otorf, Nobuyoshi Endo2), Sukehiro Kameko3), Shigeki Yokoyama4), Masaaki Ogawa5), Hiroshi Shiraki6), Hiroyuki Ikeda7) and Tsugikazu TOIXO~O~) 1)Hokkaido Blood Center, 2)Miyagi Blood Center, 3)Kanagawa Blood Center, 4)Kyoto Blood Center, 5)Osaka Blood Center, 6)Fukuoka Blood Center, 7)Plasma Fractionation Center, The Japanese Red Cross Society, Japan



321 BmT--BEAT ESTIXATION OF ARTERIAL LOADING SYSIml AND twiTmAL EmKc om!Pul! pRBII(IT1U.l lxJIutG IzPr vJm!RI- ASSIST m C E PuMeING

During LVAD pumping, it w u l d be supposed that both the natural hear t and the a r t i f i c i a l hear t share t h e same ar ter ia l system. And i n our i n s t i t u t e , t h e LVAD o u t p u t i s moni tored by electromagnetic f l m t e r on a real time base. The objective of t h i s study is to estimate the c h a r a c t e r of a r t e r i a l loading system a t every LVAD beat ing , and t o p r e d i c t t h e n a t u r a l h e a r t output on a beat-to-beat basis. The exponential e longat ion of t h e d i a s t o l i c a r t e r i a l p ressure accoring t o t h e windkessel theory a1 lows t o decompose t h e series o f a r t e r i a l p r e s s u r e waveform into a simple pressure waveform due to a smgle eject ion (s ingle pressure waveform). Thus, i t becomes p o s s i b l e t o d e r i v e t h e s y s t e m i c vascular r e s i s t a n c e and t h e a r t e r i a l t r a n s f e r f u n c t i o n a t e v e r y LVAD b e a t i n g b e s i d e s co- p u l s a t i o n , and t o p r e d i c t t h e n a t u r a l h e a r t output analyzing corresponding s ingle pressure waveform w i t h t h e s e parameters. F i r s t , t h e s e method were evaluated in mock circulatory loop The in-vitro study revealed that in comparison t o electromagnetic f l a m e t r y , t h e SVR methd and the t r a n s f e r func t ion method y ie lded r of 0.97 (y=-O.33+1. Ox) , r of 0 .98 (y=1.4+1.Ox) , respec t ive ly . Second, they a r e evaluated i n animal experiment. The r e s u l t is t h a t t h e SVR wthod and t ransfer function method yielded r of 0.88 (y=2.0+1.3x) , r of 0.89 (y=2.4+1.2x), respec t ive ly . Both of t h e s e methods can are supposed to be useful for clinical application. H.Sekii, H.Takano, Y.Taenaka,H.Nda, E.Tatsumi M.Kinoshita, A.Yagura, E.Sasaki, T.Akutsu, National Cardiovascular Center, Osaka, Japan

323 BZNEFICIAL EFFECT O F LIPOSOMAL ENCAPUSULATED SUPEROXIDE DISMUTASE ON ISCHEMICALLY I N J U R E D LIVER I N THE RAT

Superoxide d ismutase (SOD) has been known a s a h r g h l y s p e c i f i c scavenger of superoxide a n i o n s , oxygen-derived f r e e r a d i c a l s , which c a u s e r e p e r f u s i o n i n j u r y t o t h e i schemic l i v e r . However, i t have been a l s o known t h a t SOD has a s h o r t h a l f - l i f e w i t h poor a f f i n i t y t o t h e l i v e r . NOW l iposomal e n c a p s u l a t e d SOD (L-SOD) i s e x p e c t e d t o e l i m i n a t e t h e s e d e m e r i t s of SOD. A experiment was performed t o i n v e s t i g a t e e f f e c t s of L-SOD on r e p e r f u s i o n i n j u r y t o t h e ischemic l i v e r of t h e r a t .

Two groups of Wister male r a t s underwent h e p a t i c i schemia f o r 90 minutes . I n group I , L-SOD was g iven 5 minutes p r i o r t o i schemia and t o r e p e r f u s i o n o f p o r t a l v e i n and h e p a t i c a r t e r y . I n group 11, i t s s o l v e n t was g iven . 6 hours a f t e r r e p e r f u s i o n , b o t h groups w e r e s a c r i f i e d t o o b t a i n blood samples f o r t h e l i v e r f u n c t i o n t es t .

The recovery r a t e of b i l e f low i n group I w a s s i g n i f i c a n t l y h i g h e r t h a n t h a t i n group I1 ( p < O . O l ) . Serum l e v e l s i n GOT, GPT and LDH i n group I were s t a t i s t i c a l l y lower t h a n t h o s e i r i group I1 (p<O.O5). These d a t a sugges ted t h a t L-SOD had b e n e f i c i a l e f f e c t s on r e p e r f u s i o n i n j u r y of t h e i schemic l i v e r .

__ S w s h i Senga, Atilyosi Onituka , Ha j ime Hirose , Kiiiya Yanianoto, Kunihiro Niwa The 1st Dept. of Surgery, Gifu Univ. School of M . ? d . , Sendai Shakaihoken Hosp. TOSHO Co., Japan

322 DIFFERENCE I N INSULIN INFUSION ALGORITHM OF ARTIFICIAL PANCREAS AFFECTS ITS INFUSION PATTERN BUT NOT TOTAL INFUSION AMOUNT

Marked d i f f e r e n c e i n i n s u l i n i n f u s i o n r a t e s by two commercial ly a v a i l a b l e a r t i f i c i a l endocr ine pancreas(Biostator;Miles, STG-11A; Nikkiso) was o b s e r v e d . To c l a r i f y w h e t h e r o r n o t t h i s d i f f e r e n c e d e p e n d s on c o m p u t e r a l g o r i t h m , 3 4 d i a b e t i c s were c o n t r o l l e d w i t h two closed-loop glycemic c o n t r o l systems on s e p a r a t e day. For glycemic c o n t r o l w i t h E i o s t a t o r , small g a i n s of parameters (Bios ta t0r -S ; sugges ted by C h r i s t i a n s e n et a l ) and l a r g e r g a i n s of p a r a m e t e r s ( E i o s t a t 0 r - L; sugges ted by t h e U l m group) were a p p l i e d .

I n s u l i n i n f u s i o n r a t e showed a p u l s a t i l e f a s h i o n p o s t p r a n d i a l l y w i t h B i o s t a t o r - S , o r Eios ta tor -L . Eios ta tor -L i n f u s e d a s i g n i f i c a n t l y l a r g e r i n s u l i n dose f o r d a i l y c o n t r o l ( 6 8 . 5 ~ 5 0 ) than Biostator-S(59+15U) or STG-I1A(50+22U). STG- 11A a n d B i o s t a t o r - S a l s o n o r m a l i z e d d a i l y g l y c e m i c e x c u r s i o n s . E i o s t a t o r - L s u p p r e s s e d p o s t p r a n d i a l glycemias more remarkably.

T h e s e d a t a i n d i c a t e t h a t d i f f e r e n c e i n computer a l g o r i t h m of a r t i f i c i a l e n d o c r i n e pancreas a f f e c t s t h e i n s u l i n i n f u s i o n p a t t e r n , but no t t h e d a i l y i n s u l i n i n f u s i o n amount when t h e i r c o n t r o l parameters a r e s e t a p p r o p r i a t e l y t o each d i a b e t i c p a t i e n t .

M.Sekiya ,* Y.Yamasaki , M.Kubota, R.Kawarnori, M.Shichir i , T.Kamada. F i r s t Dept. of Med., Osaka Univ. Med. School , *Dept . o f M e t a b o l i c Med., Kumamoto Univ . Med. School .

324 HFSKDYhLAMIC STUnIES DU!?IPJG VENO-A?TXXIAT, EM3 (VA-ECMO) WITH AN AUKNAT1CALL.Y DRIVEN BJmD PUP

PJthough VA-ECM3 became popular for t reat ing neonatal respj-ratory fai lure , hmdynaxics during VA-Fu'x), especially e f fec t on the heart has not k e n investigated extensively. W e developed an unique V A - ~ c i rcu i t of 65 m l priming volume by using an automatically driven blood pump instead of a conventional ro l le r pump. Our previous experiments demnstrated tha t s m a l l anjmals tended to develops hypotension and ended up circulatory fai lure during high f l o w V R - K W . Hemdynamic studies were undertaken on 1 6 puppies. Hemdynamic parameters were mnitore2 with pressure transducers and electromacjnetic flow probes and were recorded on a mltichanneled polyqraph. Results: C a r d i a c output, man PAP, and LAP f e l l gradually and progressively as bypass flow increased. I t was found tha t LV systol ic pressure gradually elevated i n sp i te of steady fiecrease in f e m r a l Al? a t high flow bypass as much as 70 ml/kg/min, though T,V systol ic pressure w a s equal to femoral Ap a t low flow bypass. The 2iscrepancy of the systol ic 2ressure hetween l e f t ventricle and femoral ar tery remained unchanged even a f t e r bypass flow was reduced from the maximal hypass flow ra te (100ml/kg/min). RV and LV end-diastolic pressure decreased s ignif icant ly a t low bypass flow rate , but elevated as bypass flow increased over 50-60 ml/kg/min. These findings suggested that biventricular s t ra in was closely related to hypotension under high flow VA-ECMO Takahiko Seo, Takahiro Ito, Hiropki Takagi kpartment of Surgery, Branch Hospital; Nagoya IJniversj.ty School of WxIicine, Nagoya, Japan



325 02 and CO2 Permeabilities of Solvent-Casted Polyurethane Nembranes

The aim of this study is t o investtgate the possibiltly of using microporous polvurethane membranes WJJ prepared FY solvent CaStlnq. as the mas2 transfer rate controlling membrane in membrane oxygenator appl tca lions. Polyurethane membranes with different s t r u c t u r ~ l properties and thickness (20-75 PI were obtained by using different solvent systems (THF, dioxane. X 10 OMF-THF and % 10 DMF- dioxane) and precipitation medium (X 20 glycerol-flater). Structural and rnechanical properties o f these membranes were analyzed by SEN and tenslle stress-strain tests, respectively. 02 and CO2 psrmeatilities of PU membranes by the eyperiments carried aut in pas transfer units at different temperatures and ttte gas phase pressure and results were compared with microporous polypropylene membranes Results obtained in this study may be summarized as follows. * IJsinq different solvent(s1 and non-s@lvent(s) systems and by changiriy the casting polymer %lm thickness. polyurethane membranes with lnw porosities to highly porous, therefore wi th different mass transfer and mechanical properties may be prepared by solvent casting.

Pure solvenl (THF) and pond non-solvent (water) give a finger type pore structure with low porosities. While. good solvent ( XI0 DtlF- dinksanl and poor non-solvent ( Z 20 glycerol-water) give a highly ~ o r u u s . sponge type stuctures with open pores. * O:, l r an j fe r through PU membranes i 5 significantly affected by the solvent/non-solvent systems used, and thereiore by the pore structure and porozity o f the membrane. While these efects are less important in SO: transport. High gas transier rates may be achieved at higher temperatures and gas phase pressure, and with thin membranes.

A . I . SERBETil. E.PISklN Hacettepe Universiti', Chemtcal Engineerin Dept.. Ankar3,Turkey

327 I N VIVO ESTIMATION OF HIGHLY PERMEABLE MeMBRANE DIALYZER (HPD) BY DEXTRAN CLEARANCE -

In-vivo estimation of efficacy of middle molecular substance reduction with HPD was tried by measurement of dextran clearance (DC).

40 mg/kg of Dextran 40 (Midori Jyuji) was injected before dialysis to 20 uremic patients. DC were measured at lhr. after start of dialysis with polysulfone(PS), PAN, EVA, PMMA and conventional Cuphrophane(C) dialyzers by volumetric ultrafiltratin control system. Dextran concentrations were measured by high performance liquid chromatography (HPLC) by TSK-G3000-SW.

DC at 5k dalton agreed well with inulin clearance. DC at 15000 dalton also agreed with beta-2 micro-globulin clearance. Molecular weight-clearance curves(MCC) of PMMA and PS definitely showed significant efficacy in eliminating high molecular weight substances around 60k dalton. In contrast, MCC of PAN, CA, and EVA showed only significant clearance at less than 40k dalton. MCC less than 10.4k dalton were not different between these dialyzers except C.

We conclude that DC by HPLC is useful in characterizing the functional differences among several HPD. - T. Shibamoto, T. Akiba, T. Yamada, Y. Iino, Y. Ohshima. Kidney Center, Tokyo Med & Dent Univ. Tokyo Japan.

3% EFFECT OF PHYSICO-CHEMICAL PROPERTIES OF POLYMER MATERIALS ON THE I N I T I A L STAGES O F CALCIFICATION.

The processes of human serum albumin and calcium adsorp t ion were s tud ied under G i f f e r e n t condi t ions modelling t h e l o c a l changes on blood/polymer i n t e r f a c e and provoking c a l c i f i c a t i o n . The experiments were h e l d wi th f r e s h human serum with f ixed a d d i t i v e s of calcium chlor ide /mo- d e l of l o c a l hypercalcemia/ o r of satu- r a t e d longchain f a t t y a c i d - potassium pa lmi ta te /model of hyperlypemia/. The comparison of t h e adsorpt ion processes under these d i f f e r e n t condi t ions revealed t h e p r e f e r e n t i a l adsorpt ion of calcium complexes with l i p i d s o r l i p i d s and pro- t e i n s over t h e calcium complexes only w i t h pro te ins . To analyze t h e poss ib le mechanism of competit ive adsorpt ion of ion ized calcium and calcium complexes the experiments w i t h model s o l u t i o n s / T r i s , serum albumin, calcium chlor ide , f a t t y acid/ were held. The q u a n t i t i v e paramet- r e 3 descr ibed t h e adsorpt ion curves of calcium as a func t ion of f a t t y a c i d con- c e n t r a t i o n s were suggested.I t w a s shown t h a t these parameters depended on t h e na- t u r e of t h e polymer, i n p a r t i c u l a r , on value and the c h a r a c t e r of d i s t r i b u t i o n of d i s p e r s i v e and p o l a r components of t h e s u r f a c e f r e e energy.

1nst .of Transplantology and A r t i f i c i a l Organs, MOSCOW, USSR

Sevast ianov V.I., Rosanova I.B.

328 HEMOFILTRATION FOR THE PREVENTATION OF MYONEPHRO- PATIC METABOLIC SYN!JROME(MNMS)IN THE CASE OF ACUTE ARTERIAL OCULUSION

This is t h e f i r s t exper imenta l and c l i n i c a l s tudy f o r t h e hernof i l t ra t ion therapy on purpose to e l i m i n a t e t h e t o x i c subs tances induced MNMS i n t h e case of a c u t e a r t i r i a l oculus ion (AAO).

t h e l i g a t i o n a t the i n f r a r e n a l a o r t a and t h e b i l a - t e r a l femoral a r t e r i e s a s t h e expr imenta l model of AAD .

A f t e r 24hours from t h i s t r e a t m e n t , t h s e s l i q a - t i o n s were r e l e a s e d and then throrbectomy w a s done.

One group was g iven no t rea tment and t h e o t h e r group w a s t r e a t e d by h e m o f i l t r a t i o n .

C l i n i c a l l y , t h r e e c a s e s under t h e expec t ion of MNMS were t r e a t e d by h e m o f i l t r a r i o n . The serum con- c e n t r a t i o n of myoglobine, CPK, potassium and o t h e r s e v e r a l a g e n t s a s t h e t o x i c subs tanas induced MNMS were measured b e f o r e and a f t e r t h i s hernof i l t ra t ion .

On t h e experimental d e t a , 5 o u t o f 1 5 i n c o n t r o l group were d ied . All i n t h e t rea tment group was survived. The c o n c e n t r a t i o n s o f t h e t o x i c subs tances i n the t r e a t e d group decreased s i g n i f i c a n t l y com- p a i r e d w i t h t h e c o n t r o l g r o u p ' s . On t h e c l i n i c a l c a s e s , t h e r e were keeping l o w v a l u e s a f t e r t h e hemo- f i l t r a t i o n .

The r e s u l t sugges ted t h a t h e m o f i l t r a t i o n was v a l u a b l e t r e a t m e n t for t h e prevent ion of MNMS by t h e e l i m i n a t i o n of t h e t o x i c subs tances i n the case of a c u t e a r t e r i a l oculus ion .

On t h i s s tudy , 45 mongrel dogs w e r e t r e a t e d wi th

M i e Shhamura , Hideo Hagiwara, S e i r y u Ni ino . Xideo Maeda , Masao Ich iwata , Katsuyuki Suzuki , Hideo Kohno, Takeo Watara i , Yukiyasu S e z a i The 2n Department of Surgery, Nihon U n i v e r s i t y , School of Medicine, Tokyo, Japan



329 EARLY RESULTS A N D V A L V E FUNCTION OF M E D T R O N I C HALL VALVES

This s tudy was designed t o e v a l u a t e t h e e a r l y r e s u l t s of Medtronic-Hall(M-H) v a l v e s . 57 va lve replacements were performed wi th M-H v a l v e s i n 48 p a t i e n t s f r o m 1987 t o 1988. The p a t i e n t s c o n s i s t e d of 70 males and 28 females , and t h e age o f them r a n g e d from 1 6 t o 61 (mean 5 1 . 2 ) . 23 va lves were implanted i n t h e m i t r a l p o s i t i o n , 16 i n t h e a o r t i c p o s i t i o n and 9 i n both t h e m i t r a l and t h e a o r t i c p o s i t i o n s . The t o t a l fo l low up F f r i o d was 52.5 p a t i e n t y e a r s . There were t h r e e h v s p i t a l d e a t h s ( 6 . 3 % ) a n d o n e l a t e d e a t h (1 .9%pt-yr ) . P r o s t h e t i c va lve e n d c a r d i t i s a f t e r AVR was observed i n 2 p a t i e n t s (3 .8%pt-yr ) . We a l s o eva lua ted t h e va lve response t o tachycard ia u n d e r t h e r i g h t v e n t r i c u l a r p a c i n g . When t h e r a c i n g r a t e exceeded 120 p e r m i n u t e , C . O . was decreased i n t h e DVR p a t i e n t s . However i n the Y\'R p a t i e n t s , C . O . was n o t d e c r e a s e d u n l e s s pacing r a t e was over 130. The M-H va lve f u n c t i o n t r a n s p l a n t e d i n the m i t r a l p o s i t i o n w a s eva lua ted k i t h pulse doppler echocardiography and compared k i t h t h e r e s u l t s of t h e Bjork-Shiley Monostrut (E-S) valves . The peak va lve pressure g r a d i e n t vere measured i n t h e 18 cases with M-H va lves and i n t h e 70 c a s e s with B-S va lves . The peak va lve g r a d i e n t of t h e 27 mm M-H va lves was 7 .5 mmHg and E,-S 8 .7 mmHg. The g r a d i e n t of t h e 29 m m M-H va lves was 6.5 mmHg and B-S 7.1 mmHg. Thus, no E t a t i s t i c a l l y s i g n i f i c a n t d i f f e r e n c e was observed tetween the M-H va lves and t h e B-S va lves i n t h e va lve g r a d i e n t . These r e s u l t s a r e c o n s i s t e n t with t h e conclus ion t h a t t h e Medtronic-Hall valve i s e.n acceptab le p r o s t h e s i s f o r va lve replacements . I'akatsugu Shimono, Kazuhisa Shikano, I s a o Yada, lrlj noru Kusagawa, Depart . of Thoracic Surgry Mie I k i v . , Tsu, Japan

331 CARPAL TUNNEL SYNDROME A N D SHOULDER STIFFNESS I N LONG-TERU HEMODIALYSIS FAT I ENTS

far more t h a n 10 y e a r s , 11 d e v e l o p e d c a r p a l t u n n e l syndrome(CTS) a n d 16 developed s t i f f n e s s of bo th s h o u l d e r s ( S S ) . Among 11 w i t h CTS, 6 &'ere o p e r a t e d a n d 8 w e r e accompanied b y SS. We i n v e s t i g a t e d t h a t t h e r e were s e v e r a l s i g n i - f i c a n t d i f f e r e n c e s be tween t h e g r o u p of patients w i t h a n d ' wi thout CTS. Compar ing t h e s e two g r o u p s , t h e CTS g r o u p w a s older a n d h a d much h i g h e r l e v e l a n d g r e a t e r increment of se rum a l u m i n u m ( AAl) a f t e r i n f u s i o n of d e s f e r r i o x a m i n e (DFO). hioreover t h e symptomatic group had much h i g h e r a v e r a g e v a l u e of serum 8,-microglobul in (BMG) i n p a s t s e v e r a l y e a r s before development of t h e symptom t h a n t h e o t h e r g r o u p . I n match- e d a n a l y s i s f o r a g e a n d d u r a t i o n of d i a l y s i s , we o b s e r v e d s i m i l a r s e r u m A 1 l e v e l a f t e r DFO i n f u s i o n . And we found t h a t t h e g r o u p of p a t i e n t s w i t h SS w a s o l d e r , h a d much l o n g e r d u r a t i o n of d i a l y s i s a n d h a d much h i g h e r level a n d g r e a t e r A A ~ a f t e r DFO i n f u s i o n , t h a n asym- p tomat ic g r o u p . T h u s , we came t o t h e conclusion that more a t t e n t i o n should b e a c t u a l l y given not o n l y t o a g e , d u r a t i o n of d i a l y s i s a n d serum BMG l e v e l , b u t t o a c c u m u l a t i o n of A1 as c a u s a t i v e a g e n t of CTS a n d / o r SS i n p a t i e n t s u n d e r g o i n g long-term h e m o d i a l y s i s .

Among 57 p a t i e n t s u n d e r g o i n g h e m o d i a l y s i s

1 5 4 . 6 I 178 .8 I 167.3 1 54.2 46 1 46.4 1 168.1 I 124.6 I 45.8

1 p<0.051 n s I p < 0.05 1 p C0.05

] . S h i n 9: , Y . F u j i t a * :k , S . I noue * * , H . Mor i ii $c , 0. I n a g a k i * " , R.Sakai*"'\, M.Nishioka""* , K Komaba""" H.Okudaira""* !;tiihokushin 'HD Cl in ic* , Hyogo Col lege of Medi- c:lne**, Sumiyoshigawa Hospi ta l"$r*, Kobe, J a p a n

330 INVESTIGATION OF PAFAMEEX ESTIMATOR AND ADAPTIVE CONTROLLER FOR ASSIST PUMP BY COMPUTER SIMULATION.

The parameter estimation and adaptive c o n t r o l of pneumatic assist pump was s t u d i e d .

For the e s t i m a t i o n of sys tem parameters, second order s i n g l e input - single o u t p u t AR(auto- regressive) models are in t roduced . The c o n t r o l l e d o u t p u t is m e a n arterial pressure(mAoP), mean a t r i a l pressure(mLAP), or m e a n blood f low and t h e control i n p u t is vacuum pressure of t h e pump. Recursive least- squares method is used t o estimate the parameters . Based on t h e es t imated parameters, c o n t r o l l e d o u t p u t s i n s teady state w i t h g iven vacuum p r e s s u r e s are predicted, and d e s i r e d vacuum p r e s s u r e minimizing t h e performance index is searched. The performance index is weighed summation of square errors.

F e a s i b i l i t y of parameter estimator and c o n t r o l l e r w a s demonstrated a g a i n s t the v a r i o u s changes i n t h e c i r c u l a t o r y c o n d i t i o n by the computer s imula t ion . I n one example, l e f t ventricular c o n t r a c t i l i t y suddenly decreased , the n a t u r a l h e a r t ejected no f l o w , and a d d i t i o n a l l y p e r i p h e r a l resistance increased by 5% a t the same time. mAoP dropped ( 1 1 L 97.5mmHg) and mLAp rose ( 3 + 4.2mmHg) i n s t a n t a n e - ous ly . But the controller smoothly r e s t o r e d t h e d e s i r e d s t e a d y state (MOP o f 114rmnH9, mLAp of 3.0mmHg) a f t e r 30 beats.

The developed c o n t r o l l e r a d a p t i v e l y c o n t r o l l e d t w o v a r i a b l e s ; m e a n arterial and atr ia l pressures, a g a i n s t the v a r i o u s chanqes of c i r c u l a t i o n system. The estimator and controller can work on a personal computer.

T o s h i w k i S h i m k a , Yoshinor i Mitamura, Toshio Yuhta. School of Eng., Univ. of Hokkaido, Sapporo, Japan

332 CLINICAL EVALUATION OF THE RATE HISTOGRAM SYSTEM IN RATE RESPONSIVE PACEMAKERS

Rate responsive (RR) pacing become more important in pacemaker therapy. Different sensors of metabolic demands of the body are available to regulate the pacemaker rate. Most of them, however, do function independently of an atrial electrogram, so that it is necessary to determine most suitable point of RR parameters for the best programming by treadmill ergometry or Holter ECG monitoring. The purpose of this study was to access whether the Rate Histogram does function as an determinant system of main parameters for RR pacing. Methods: Sensolog 703 was implanted in 10 patients with pathological bradyarrhythmias and follwed up both with the Rate Histogram and by Holter ECG up to 6 months after implantation. Ten healthy persons were monitored by Holter ECG in daily life and heart rate changes was analysed. Results and Conclusion: 1. The Rate Histogram with 4 bins rate classification represented different types of heart rate distribution according to patients symptoms, sensor rates, reaction time and recovery time. 2. Judging from heart rates analysis of healthy control group, the Rate Histogram is simple and easy system to determine suitable RR parameters with short term exercises. It also provides long term information. 3. Six bins heart rate clasification will provide more useful pattern of heart rate distribution to determine the best programming compared with current 4 bins.

Goki Shindo, Akira Furuse, Kenji Kozeni, Go Kawaguchi, Makoto Takeda Dept. of Thracic Surgery, Faculty of Medicine, University of Tokyo, Tokyo, Japan



333 CELLULAR PERFORMANCE OF THE I N V I T R O SEEDED ENDOTHELIAL CELLS I N HYBRID VASCULAR PROSTHESIS

There a r e many r e p o r t s t h a t v a s c u l a r e n d o t h e l i a l c e l l s (ECs) d i d not adhere w e l l t o s y n t h e t i c g r a f t m a t e r i a l s and s u r f a c e modi f ica t ion such a s co l lagen c o a t i n g was necessary f o r t h e complete monolayer formation. On t h e o t h e r hand endothe l ia l c e l l s i n c u l t u r e a r e capable of condi t ion ing t h e i r environment inc luding s y n t h e s i s of endo- geneous e x t r a c e l l u l a r matr ix . The purpose of t h i s s tudy i s t o examine the e f f e c t of ECs seeding i n high d e n s i t y on t h e non-coated m a t e r i a l . A s a m a t e r i a l low poros i ty ve lour woven p o l y e s t e r f a b r i c s without c o a t i n g of adhesive p r o t e i n was used. Canine venous E C s and human saphenous v e i n E C s were harves ted enzymatical ly and c u l t u r e d . The ECs suspension i n c u l t u r e medium was f lushed through t h e f a b r i c s (2-3X105 c e l l s / c m 2 ) . The specimens were examined on f a c e chronologica l ly with l i g h t microscope a f t e r b i o l o g i c a l s i l v e r s t a i n i n g and nucleus s t a i n i n g . The ECs a t tached around each f i b e r s t r e t c h i n g l o n g i t u d i n a l l y and they could a c q u i r e h igher d e n s i t y t h a n seeding onto a smooth s u r f a c e . The ECs were found t o grow a p a r t from f i b e r s t o make c e l l u l a r j u n c t i o n each o t h e r and p a r t l y made i n i t i a l c e l l u l a r l i n i n g a c r o s s f i b e r s i n a few days. Afterwards they formed a conf luent monolayer on t h e f a b r i c s . I n conclus ion , ECs i n high c e l l u l a r popula t ion make a conf luent monolayer on the i n n e r s u r f a c e of t h e hybr id v a s c u l a r p r o s t h e s i s wi thout s u r f a c e modifi- c a t i o n .

Motoaki Shirakawa, Atuhiko Takagi, Shunya Shindo, Yusuke Tada, Yasuo Idezuki , Shouzi Nagaoka”, The Second Dept. of Surg. Univers i ty of Tokyo, Tokyo, *Toray Basic Research Labora tor ies , Kanagawa, Japan

335 MCAL APPLICATION OF OXYGENATED PERFLUROCHEMICALS FOR TISSUE OXYGENATION

This s tudy aimed a t p r e d i c t i o n of in t ramura l hypoxia i n stomach and sigmoid colon and t o in- c r e a s e l o c a l t i s s u e oxygenat ion. G a s t r i c i n t r a - mural pH was measured by tonometry. Index of oxygen s a t u r a t i o n (IS02) and index of hemoglobin ( I H B ) s a t u r a t i o n was measured by r e f l e c t a n c e spectrophotometry. G a s t r i c ischemia was produce by hemorrhagic shock model i n 20 mongreal dogs. In t ramura l pH 7.24 w a s considered c r i t i c a l f o r mucosal l e s i o n s development ( normal va lue 7.45 + 0 . 3 ) . Af te r one hour d u r a t i o n of shock IHB decrease from l O O + l O t o 3056 and IS02 decrease from 4026 t o 552. Stomach was i r r e g a t e d w i t h oxygenated per f lurochemica ls 2 O % ( F D A ) when i n t r a - mural pH drop below 7.24. In t ramura l pH was maintained above 7.24 i n FDA t r e a t e d group on t h e c o n t r a r y i n u n t r e a t e d group p H decreased p e r - s i s t e n t l y . I n FDA t r e a t e d group IS02 increased from 552 t o 27+6 (p<O.Ol). Index of h i s t o l o g y i n j u r y was lower i n t r e a t e d group ( ~ 4 0 . 0 5 ) . Tonometry i s a l s o u s e f u l f o r t h e p r e d i c t i o n of sigmoid colon ischemia. FDA can temporary sa lvage t h e i n t e s t i n a l ischemia which may have p o t e n t i a l c l i n i c a l a p p l i c a t i o n t o augment t h e golden t i m e necessary f o r r e v a s c u l a r i z a t i o n . S i g n i f i c a n t amount o f a r t e r i a l oxygen can be d e l i v e r by p e r i t o n i a l lavage w i t h FDA.

Shozo Baba, Matin A.F.M. The 2nd Dept. of Surgery, Hamamatsu Univers i ty School of Medicine, Hamamatsu, Japan

334 CORRECTING METHODS OF PLASMA BETA-2-MICROGLOBULIN (B2M) LEVELS DURING HEMODIALYSIS (HD) WITH CONVEN- TIONAL DIALYZERS

It i s w e l l known t h a t B2M concent ra t ions in- c r e a s e s i g n i f i c a n t l y dur ing HD with convent ional cuprophan d i a l y z e r , even i f they a r e c o r r e c t e d by hemoconcentration e s t i m a t e d w i t h hematocr i t or t o t a l protein(Method 1). Recent ly , Bergstroem e t a l . have r e p o r t e d t h e c o r r e c t i n g formula(Method 2 ) , i n which d i s t r i b u t i o n volume of f r e e B2M w a s assumed t o be i d e n t i c a l t o e x t r a c e l l u l a r volume. I n o r d e r to e v a l u a t e t h e adequacy of t h e s e cor - r e c t i n g methods, changes i n B2M and myoglobin(Mb) l e v e l s were measured dur ing HD i n 40 s t a b l e HD p a t i e n t s . I n HD w i t h o r d i n a r y composition o f d i a l y s a t e ( H D l ) , B2M by t h e c o r r e c t i o n wi th method 1, i n c r e a s e d a t t h e end of HD(p< 0 .01) . Although B2M a l s o increased dur ing HD w i t h h igh sodium dia lysa te (HD2) , es t imated by t h e same c o r r e c t i n g method(p(O.Ol) , t h e i n c r e a s e was less i n H D 2 than i n HDl(p<O.OS). showed no s i g n i f i c a n t i n c r e a s e e i t h e r i n H D 1 o r HD2, and B2M a f t e r t h e c o r r e c t i o n remained t o be w i t h i n 10% of pre-HD v a l u e s i n two- th i rd of t h e p a t i e n t s . The method 2 f a i l e d t o c o r r e c t B2M. when changes i n plasma osmolal i ty(Posm) by HD were very l a r g e or smal l , r e f l e c t i n g t h e water r e d i s - t r i b u t i o n between i n t r a and e x t r a c e l l u l a r space . The s i m i l a r f i n d i n g s were observed i n t h e a l t e r a - t i o n s i n Mb l e v e l s . These r e s u l t s i n d i c a t e t h a t Bergstroem’s formula i s adequate and u s e f u l f o r t h e c o r r e c t i o n of B2M and Mb, however f o r t h e more e x a c t de te rmina t ion , t h e changes i n Posm must be taken i n t o cons idera t ion . Kanj i Shish ido , Tadao Akizawa, Shozo Koshikawa Department of I n t e r n a l Medicine, Fuj igaoka H o s p i t a l , Showa Univers i ty , Yokohama, Japan

Corrected w i t h method 2 , B2M

336 HYBRID ARTIFICIAL IXART I n 16 e x p e r i m e n t s we a p p l i e d a s s i s t

c i r c u l a t i o n i n combina t i o n w i t h s o - c a l l e d h y b r i d a r t i f i c i a l h e a r t (HAH) as a ’ b r i d e e b e f o r e h e a r t t r a n s p l a n t a t i o n . The v e n t r i - c u l a r c a v i t y w a s u s e d t o d t s c h a f p e b l o o d , w h i l e n a t u r a l v a l v e s p r o v i d e d u n i d i r e c t i o - n a l b l o o d f low. HAH c o n s i s k d o f 2 s i n g l e - c o n n e c t e d v a l v e l e s s pumps, “ c o n n e c t e d w i t h the c a v i t y o f c o r r e s p o n d i n g h e a r t v e n t r i c l e v i a s h o r t wide c a n n u l a e , i t h a s been deve- l o p e d and t e s t e d i n c a l v e s . A t h i n r i g i d c a s i n g ( c a r d i o s s s i s t o r ) w a s p l a c e d on t h e o u t s i d e o f myocardium. The pumps f u n c t i o n - ed i n c a r d i o s y n c h r o n i z e d mode and were f i l l e d w i t h b l o o d i n d i a s t o l e , w h i l e i n . s i s t o l e t h e y e n s u r e d t h e b l o o d o u t f l o w t o t h e v e n t r i c u l a r c a v i t y a n d , f u r t h e r t o t h e a o r t a . The e x t e r n a l c a s i n g l i m i t e d t h e hear t w a l l d i s t e n t i o n i n t h e moment of i n - t r a v e n t r i c u l a r o u t f l o w . T h o bench tes ts showed tha t at the-moment o f o u t f l o w t h e v e n t r i c u l a r v a l v e s r a i s e d and c l o s e d t i g h t - l y up w i t h o u t a n y v i s i b l e r e g u r g i t a t i o n .

The e x p e r i m e n t s p r o v e d a h i g h e f f i c i e n c y o f HAH d u r i n g 24 h o u r s o f f u c t i o n i n g .

V a l e r y I. Shumakov, V l a d i m i r E. T o l p e k i n , Leonid F. Koblov, A. N. Baikov I n a t . o f T r a n s p l a n t o l o g y & A r t i f i c i a l Organs. M i n i s t r y o f Heal th , Moscow, USSR-


ABSTRACTS OF THE V I M WORLD CONGRESS 36 7

f o u r v e r s i o n s o f ALI) I 0 2 t imes i n 76p~f%$ en t s . Version 1: flow blood s e p a r a t o r 1 ow flow membrane oxygenator-heatexchan- ~,er,'LFlYiO-HE/"10ST" and r o t o r of blood se- p a r a t o r PK05 with i s o l a t e d hepatocytesiIE. ere Soin consequently; ve r s ion 2-plasm~i-

blood s e p a r a t o r wen/ vers ion 3 3'3-03 LFMO ''MO,T'', massexchenger /ME/ i s loaded by cepsu le s wi th I H ; ve r s ion 4: p l a s m a f i l t e "Cambro", LFMO "MOST", ME. We used i n AL both f r e s h i s o l a t e d hepa tocy te s , a n d hepa tocy te s a f t e r d i f f e r e n t pe r iods of cryc p r e s e r v a t i o n s [ f r o m 1 week t o 4 monthesl. I n t h e fol iowing c a s e s we used d i f f e r e n t ve r s ions o f ALD: fulminant acu te v i r u s he p a t i t i s / A V H / B wi th h e p a t i c encephalopa- t y / H E / I L L - i \ : st.-13; acu te condi t ion of chronic e c t i v e h e p a t i t i s and cirrosis ;nit2 HE 21-111 st. ; Wilson's diseas-23; femil) hypercholesterinemia-6; mechanical jaundice-32; polyorganic i n s u f f i c i e n c y syndrome /I'CIS/ w i th HE 1 1 1 - I V st.-?. I n group with f'ulrninant riVH 4 among 13 pa t i en te cliee, i n group with c i r ros i s - ' I and i n g r c u? with POIS-all p a t i e n t s d i ed a f t e r 7-8 tiajrs.In o t h e r g r o u p s all p a t i e n t s were

f i l t e r "Gambro"/ , LFMO-HE "MOST",

337

339

THE ROLE OF MOLECUI3S AND CELLS I N CAL- C I F I C A T I O N OF HYDROPHOBIC POLYMER MATE- RIALS.

The hypo thes i s of b i o m a t e r i a l s ' c a l c i - f i c a t i o n t a k i n g account of molecular and c e l l s ' i n t e r a c t i o n of polymer m a t e r i a l s w i th blood w a s proposed and experimental- l y s u b s t a n t i a t e d . The i n i t i a l s t a g e s of c a l c i f i c a t i o n , namely , i o n r e d i s t r i b u t i o n , complexation and adso rp t ion were s t u d i e d i n experiments i n v i t r o f o r a number of hydrophobic polymer m a t e r i a l s ( s i l i c o n e rubbe r , po lye the ru re thane , polyethelene) .

The r o l e o f c e l l s i n c a l c i f i c a t i o n was i n v e s t i g a t e d i n vivo (subcutaneous implantabion i n r a b b i t s ) . The development o f c a l c i f i c a t i o n w a s observed t o proceed without d i r e c t c e l l s ' con tac t w i th sam- p l e s , without ce l l s ' death.The presence of ce l l s i n c r e a s e d the ra te and s e v e r i t y of b i o m a t e r i a l s c a l c i f i c a t i o n , but t h e calcium d e p o s i t l o n waa d e t e c t e d under cond i t ion o f t o t a l i s o l a t i o n o f t h e sam- p l e s from the c e l l s . The c h a r a c t e r of d i s t r i b u t i o n and composition of depos i t i on on t h e s i l i c o n e rubbe r s u r f a c e s were analyzed a f te r d i f f e r e n t pe r iods of implan- t a t i o n . The suggested scheme of t he cal- c i f i c a t i o n mechanism al lows t o propose the p r i n c i p l e s and methods of i n h i b i t i o n of b i o m a t e r i a l s ' c a l c i f i c a t i o n .

Shumakov V . I . ,Rosanova I.B. Sevas t i a - nov V . I . I n s t . o f Transplantology and A r t i f i c i a l Organs, Moscow, USSR

338 MEMBRANE OXYGENATORS "MOST" PIOSURGERY AND I N T E N S I V E -

*. - 122" were app l i ed i n 150 pa t i en t sdur ing a l l modern open-heart operat ions with hypothermic ex t r aco rporea l c i r c u l a t i o n (EC) including donor h e a r t t r a n s p l a n t a t i o n and implantat ion of a r t i f i c i a l hear t . EC ap- p l i c a t i o n l a s t e d f o r 30 mins t o 4 hours

Qhowed e f f e c t i v e gas exchange, s t a b l e he- modinamics, optimal c h a r a c t e r i s t i c s gases and blood acide-base balance, ahcence of hemolysis.

Such MO w e r e used f o r ex t r aco rporea l e l imina t ion of CO during hypercapnia i n p a t i e n t s w i t h extlemely severe asthmatic s t a t u s . During venovenous perfusion f o r 24 hours and more under blood act ivedra- inage cond i t ions ( l l /min) w e normalized CO concentrat ion i n blood and optimized a s 8 i s t e d pulmonary v e n t i l a t i o n .

single-used low-flow MO-heat-exchangers "MOST' can s u c c e s s f u l l y u s e i n c r i t i c a l condi t ions of hypoxemia duringhemosorp- t i o n , plasmapheresis, ensuring of v i ab i - l i t y ex t r aco rporea l ly connected donor,S sp l een , i n " a u x i l i a r y l i v e r " device as w e l l a s during r e t rog rade cardiosynchro- nized perfusion of coronary s inus .

Shumakov V.I . , P isarevskyi A.A. , Kara- s e v A.B.

For smell-wolume perfusion were c rea t ed

Research I n s t i t u t e of Transplantology an@ the USSB_Clinistrv of -



341 O T H E L 342 PARAMETRESINASSESSMENT OF CADAVERIC KIDNEYS ___I____ FOR RENAL TRANSPLANTATION In a rctraspective studs,the authors

re-evaluated various factbrs and circum- stances participating,in mutual relation- shipsin the resulting quality of kidneys taken from cadaverous donors. A/ age:our results indicste,that rcci - piemts of kidneys from older donors/40-

45 years old/ do not do as w e l l as those, eceiving kidneys from younger donors,B/ atients with sepsis/ TBC / are mot sui- able candidates for dolaatior,C/the pre- enceof hereditary nephritis contraindi- ate kidney donation / Alport sy /, D /tor ide / prslonged hypertension also contr). ndicated kidaey denatian,E/ earJy resto- ation of the function o q donnors kidneys ransplantated into host s organism can bk

Tith greet probability expected/p 0 , O l / hen the serum Creatinine ( 1 6 0 urel/l , otal ischeaia"30 hours ,and when the

+slut of renal index/= P (-3.500 /p==O,OOl /,F/ &eroid+ T + )insulin ,a8 well as Dopamine + Fdoseaid arc the nex t medicines ,which is necessar t o apply!G/ NMR - spectroscopy can be use$ 4 s one of methods for determination =eta- bolic changes in tissues and organs to be transplantated, H/ the most important factor negatively influencing the resulting quality / " vitrslity"/of the trans-

I i

''T x Total ischtmie

J., Zuclrn,Y.

THE ROLE OF 31 - P- NMR SEGCTROSCOPY IS ASSESSYELFT 0F"VITALITY" OF ORGANS USED W TRANSPLANTATION:

After making out their own metho- ddLw of quantitatim determination of macroergic phosphates in tissue of har - vested organs/kidneys,pancreas,liver/,thr authors watched dynamic changes of these aetabolites p r i m their preseruation. The 31P NBdIi F1 decoupled spectra were measured on the VARXAN VXR 300 NM€jlspec- trometer operating at 125 MHz for P spins.

They found out ,that the main factor determining basal level. of macroergic phosphates in harvested organs is the time so called "warm ischeria",when very quick desintegration of MP compounds /ATP,NhDP,phosphoriliz. glycids/ is present; while simultaneous increasing of anorganic phosphate which is the direct indicator of catabolic procPsses in tissup of orsrans to be transplantatea. This correlates a l s o with thp chsmes of intrac~lull ar pH. T h p aim of our study was to work out quantifiable pametres for clinical trens pl tntoloay.The pm-metres w i l l seFvc as tasic point Tor teterrnination o l : a/vicali ty of organs to be transplznta- l e e , b/imrrr,vewnt hervesting m?thods,c/ of choice cf orcservativs solutions,d/ TO L: t transdant a ti on changes in organs / with applichtion of "in viuo" zpectrose.

343 EXPEIII I I~NT hL EV.GTJATION @F €3 4CTOGZITIC3l'L OF IIJPL U'ITED POLYMERS MO- DIFIED 3Y SILATRWES 4ND GERL'IATRPhl3L

Practical assessment of biocompatibility of implants includes quantitative characteristics of i-ntensitg and reactrim rate caused by them,e.g.,evaluation of Te actogenicity degree.Biornechanlca1 studiw were performed and massive grsnulo-fibrous capsules were obsemed, that had developed following seven days around the polymer covered implants.Polyurethane PIF 155 with a 3% addition of chlormethylsi- latrane and germatranol was studied. Re- sults were expressed as percents of coq- trol;?U-155 without additions. Chlormeth- ylsilatrane results increase of capsular mass (by 78.9:Z),incresse of concentratim of DYA (by 45.?$)and hydroxyproline (by 30.8$).This points to the Stimulation of cellular proliferation and intensive collagen s y n t h e s i s . 9 t h o ~ s i l a t r a n e reduces (by 21.15) concentration of sialic acids - a characteristic component of inflammor ti.on exudate .Germatran01 increases (by 25. 3 4 ) , the concentration of hydroproxypro- line without changing the capsular mass and when reducing the concentration of DVA and RNI1,that characterizes the present substance as a one decreasing react- genicity.Thus by adding biologically active substances we can direct modification of biomaterial reactogenicity.

Slutskii L.I.,Sevastjanova N.A.,Dombrov- ska L.E. ,Mansurova L A . , Skornjakova -4.B. , Kazimirovska ja V.B. ,Voronkov I . G . Latvian Res.Inst.of Traum.B@rthop.,Riga

USSR

344 NEW DESIGN OF A N I N T E G R A L D E V I C E FOX ADSORPTION FROM WHOLE B L O O D

W i d e s p r e a d u s e of h e m o p e r f u s i o n s y s t e m 5 i s l i m i t e d b e c a u s e o f t h e c o n t a c t o f w h o l e b l o o d w i t h b i o i n c o m p a t i b l e a d s o r b e r m a t e r i a l s . T h e r e f o r e , p r e s e n t c l i n i c a l a d s o r p t i o n c i r c u i t s r e q u i r e t w o d e v i c e s : a p l a s m a s e p a r a t o r a n d a n a d s o r p t i o n c o l u m n . The a i m o f t h i s s t u d y w a s t o e v a l u a t e w h e t h e r o n e i n t e g r a l d e v i c e c o u l d p e r f o r m b o t h s t e p s . We h a v e shown p r e v i o u s l y t h a t i n t h e a b s e n c e o f n e t f i l t r a t i o n t h e r e a r e t w o d i s t i n c t f l o w p a t h s w i t h i n a p l a s m a s e p a r a t o r : b l o o d f l o w i n s i d e t h e h o l l o w f i b e r a n d a p l a s m a f l o w w i t h i n t h e f i l t r a t e c o m p a r t m e n t i n p a r a l l e l . We f i l l e d d e x t r a n s u l f a t e b e a d s i n t o t h e f i l t r a t e c o m p a r t m e n t t o a d s o r b c h o l e s t e r o l f r o m t h i s p l a s m a f l o w . 1 6 t e s t m o d u l e s w i t h 1 . 5 , 1 5 , 2 2 . 5 cm f i b e r l e n g t h were p e r f u s e d s i n g l e p a s s w i t h b l o o d o f h e a l t h y d o n o r s w i t h o u t n e t f i l - t r a t i o n . T h e d i f f e r e n c e i n t o t a l c h o l e s - t e r o l c o n c e n t r a t i o n b e t w e e n i n l e t a n d o u t l e t w a s o n a v e r a g e 2 0 % . M e a s u r e m e n t o f p l a s m a p r o t e i n s s h o w e d t h a t t h i s d e c r e a s e i n c o n c e n t r a t i o n was d u e t o a d s o r p t i o n a n d n o t t o d i l u t i o n . T h i s w o r k demon- s t r a t e s t h a t c o m p l e t e p l a s m a t r e a t m e n t , b o t h s e p a r a t i o n a n d a d s o r p t i o n , c a n b e p e r f o r m e d i n a s i n g l e d e v i c e . The d e s i g n i s g e n e r a l a n d w i l l l i k e l y r e d u c e h a r d - w a r e r e q u i r e m e n t s f o r p l a s m a t h e r a u v . _ _ G . S m o l i k , B . S c h m i d t , U. B a u r m e i s t e r , M . Hampe, H . J . G u r l a n d -_-______ U n i v . M u n i c h , A K Z O A G W u p p e r t a l , T e c h . U n i v . M u n i c h , FRG



34.5 BLOOD MICROEMBOLI (BME) PRODUCTION AND SPONTANEOUS DECREASE IN HEPARIN ACTIVITY DURING IN-VITRO CIRCULATION OF BOVINE BLOOD

Heparin activity and BME production were studied in bovine blood pumped by a Pellethanew ventricle (85 cc, with Pellethane" molded valves) connected via smooth quick-connects to a Pellethanem horseshoe-shaped reservoir (1400 cc). In each experiment, blood was collected into heparin (1.5 units/ml) by cardiac puncture from a stunned animal. The blood was transported to the laboratory in a Pellethane" bag containing no air and was filled into 3 ventricle-reservoir systems. One oE the systems received 325 mg aspirin (ASA) shortly after the onset of pumping, while the other two served as pumping and non- pumping (quiescent) controls. In the ASA-containing system and in the pumping control, blood was pumped in a full-fill/full-eject mode at 80 beatshin with 35% systole and an outlet pressure of 110/90 mm IIg. Heparin activity was measured by the activated partial t'lromboplastin time (APT) test. BME concentration was measured by a conslant pressure filtration (CPF) method in which the blood was filtered through 2Op pore filters at 20 mm Hg for 10 seconds, and the flowrate curves were evaluated from an occlusion model.

The APTT was >250 seconds at the onset of pumping and decreased with time in all systems, with the relative rate of decreaase being

pVmoine conuol> oumnine ASA blood > auiescent control and the APlT values fell to 4 0 seconds within 8 hours. The BME production increased as the APTT decreased, with the BME Concentration following the same relative pattern as the rate of APTT decrease. indicated above.

The data suggest that heparin neutralization occurs spontaneously and continously in quiescent blood exposed to this reservoir material but is more rapid under conditions of ventricle pumping. ASA appears to partially inhibit the neutralization. The decrease in heparin activity coincides with an increasing concentration of BME.

-- K. Solen, S. Mohammad, A. Pijl, P. Swier, and D. Olsen Brigham Young Univ., Provo, Utah. USA Tlniv. of Utah, Salt Lake City, Utah, USA

347 COLLAGEN MODIFICATION AND TEE CELLULAR RESPONSE

The s u c c e s s f u l u t i l i z a t i o n of col lagen-based s u b s t r a t e s i s i m p o r t a n t f o r t h e development o f m a t e r i a l s and d e v i c e s i n c o r p o r a t i n g c u l t u r e d c e l l s . A s u i t a b l e approach t o t h e improvement of co l lagen-based s u b s t r a t e s is m o d i f i c a t i o n of t h e c o l l a g e n t o m a n i p u l a t e t h e c e l l u l a r response and a c h i e v e an enhancement o f c e l l a t tachment and growth. Col lagen m o d i f i c a t i o n w a s s t u d i e d by a n i n v i t r o i n v e s t i g a t i o n o f a s e r i e s of composi te m a t e r i a l s d e r i v e d from c o l l a g e n and t h e glycosaminoglycan h y a l u r o n i c a c i d . The m a t e r i a l s were examined i n te rms of t h e response of mouse f i b r o b l a s t s and human f i b r o b l a s t s . T h e ' i n f l u e n c e of c o l l a g e n m o d i f i c a t i o n w a s moni tored i n terms of a t h r e e s t a g e p r o g r e s s i v e e v a l u a t i o n compr is ing o p t i c a l microscopy f o r c e l l morphologica l a l t e r a t i o n s , c e l l detachment and e l e c t r o n i c c o u n t i n g f o r c e l l a t tachment a n d p r o l i f e r a t i o n , and t h e incorpor- a t i o n of t r i t i a t e d thymidine f o r c e l l v i a b i l i t y . The i n v e s t i g a t i o n demonst ra ted tha t t h e c e l l u l a r response w a s i n f l u e n c e d by the composi t ion and p r o p o r t i o n of t h e i n c o r p o r a t e d h y a l u r o n i c a c i d . The d a t a o b t a i n e d c o n f i r m t h a t c o l l a g e n modif- i c a t i o n i s a s u i t a b l e means of c o n t r o l l i n g t h e c e l l u l a r zmd h y a l u r o n i c acid r e p r e s e n t a basis f o r biomaterial development.

response a n d t h e composi tes of c o l l a g e n

S a b i t a S r i v a s t a v a , S tephen D. Gorham, James M. Courtney Devro Limi ted , Glasgow, U.K. Bioengineer ing Unit,Univ.of S t ra thc lyde ,Glasgow IM

346 ASSESSMENT OF BLOOD MICROEMBOLI (BME) DYNAMIC DEVELOPMENT USLVG A CALF EX-VIVO LEFT VENTRICULAR ASSIST DEVICE (LVAD) MODEL

The dynamic process of BME production was studied by monitoring occlusive BME in ex-vivo LVADs in two calves. In each calf, a series of pulsatile LVADs (85 cc in one animal and 100 cc in another, all made of Pellethane" with Medtronic HallM valves) was connected external to the chest walI via surgically-implanted cannulae from the left atrium. In each series, an LVAD provided ventricular assist for 1-4 days (4 L/min, full-fill/full-eject) while blood samples for BME assessment were coIIected at frequent intervals via the implanted cannulae, and the LVAD was then exchanged for a new device for repeated study.

The concentration of occlusive BME was assessed by a constant- pressure filtration (CPF) technique in which each blood sample was filtered through 20p pore filters at 20 mm Hg (computer-controlled) for 10 seconds. From a mathematical model of filter occlusion, the concentration of occluding BME was calculated from each filtration flowrate curve. The technique is not affected by blood-filter interactions and is sensitive to known blood stimuli. The CPF results were cornpared with measurements of BME volume, as determined by an on- line laser light scattering microemboli detection (LSMD) method, and also were compared with hematological measuremenis.

The CPF results indicated that the concentration of occlusive BME remained at pre-change values immediately following rhe change to each new LVAD and increased during the following 3-4 hours. By comparison, the LSMD results indicated that the volume of optically- evident BME increased dramatically within minutes after the connection of a new LVAD and then decreased slowly over the following 4 hours. The early production of "soft" (non-occluding) BME is suggested, followed by development of more rigid BME at later times. The ventricle producing the highest CPF results also produced an increase i n factor XI1 concentration.

This study demonstrates the feasibility of monitoring BME prduction as a dynamic process in an anifical organ model.

K. Solen, L. Reynolds. G. Pantalos. G . Burns, S. Mohammad, G. Drumm, P. Swier, and D. Olsen Brigham Young Univ., Provo, Utah, USA, Univ. of Illinois, Chicago, Illinois, USA, Univ. of Utah, Salt Lake City, Umh, USA

348 VOLUME OF INFERIOR VENA CAVA AS A SENSOR FOR PHYSIOLOGICAL RATE RESPONSIVE PACEMAKERS

Using t h e parameters r e l a t e d t o t h e hernodynamic c o n d i t i o n s such as s t r o k e volume, p r e - e j e c t i o n t ime i n t e r v a l , s y s t o l i c t ime i n t e r v a l e t c . , i s one of t h e e x c e l l e n t method f o r c o n t r o l l i n g r a t e r e s p o n s i v e pac ing(RRP) systems. Based on t h i s a s p e c t , t h e e x t e n t of blood p o o l a t t h e v i c i n i t y of r i g h t a t r ium i n t h e i n f e r i o r vena cava(ra-IVC r e g i o n ) w a s u s e d as a g u i d e t o d e t e r m i n e t h e pac ing rate. I t is t h e purpose of t h i s s t u d y t o e v a l u a t e t h e e x t e n t of blood pool in t h i s r e g i o n as an i n d i c a t o r f o r RRP.

To monitor t h e blood volume i n ra-IVC r e g i o n , a quadpolar impedance c a t h e t e r was i n s e r t e d i n t o I V C i n mongrel dogs and p laced a t t h e v i c i n i t y of r i g h t a t r ium. Metabol ic s i t u a t i o n s were changed by t h e pyrogenic drug and h e a r t r a t e s , c a r d i a c o u t p u t and c a t h e t e r sensor output were monitored. A l t h o u g h t h e c u r r e n t l e a k a g e i s o n e o f t h e p r o b l e m i n t h i s m e t h o d , r e s u l t s w e r e v e r y encouraging , Sensor o u t p u t responded r e l a t i v e l y w e l l t o t h e v a r i a t i o n s i n h e a r t rates and c a r d i a c o u t p u t and t h u s may be a promiss ing guide for RRP.

T o s h i f u m i S u g i u r a , S i n - i c h i Togawa, S h i z u o Mizushina, Motohiko Kimura*, Y o s h i h i t o Fukui" , Morio Togawa' and Yukio Harada**

* G r a d u a t e S c h o o l of E l e c t r o n i c S c i e n c e a n d

*"1 st D e p t . of S u r g e r y , Hamamatsu U n i v e r s i t y

Research I n s t i t u t e of E l e c t r o n i c s ,

Technology, Shizuoka U n i v e r s i t y

School of Medicine

Artificiaf Organs, Vol. 13, No. 4, 1989


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DETOXICATION WITH CHARCOAL SORBENTS I N THE INTENSIVE C A R E FOR PAEDIATRIC INFEC- T I O N S

E n d o g e n o u s i n t o x i c a t i o n ( E I ) a c c o m p a n i e s c r i t i c a l c o n d i t i o n s o f i n f e c t i o u s g e n e s i s i n i n f a n t s a n d e x h a u s t s t h e i r s y s t e m o f d e t o x i c a t i o n a n d e x c r e t i o n . We c o n s i d - e r b a c t e r i a l , m e t a b o l i c , a n d m i x e d f o r m s ; t o x i c o g e n i c a n d s o m a t o g e n i c p h a s e s ; m i l d , medium, s e v e r e a n d t e r m i n a l l e v e l s o f E I . T h e s e c o n s i d e r a t i o n s p r e d e t e r m i n e d t e r m s , n u m b e r s , a n d v o l u m e s o h h a e m o s o r p t i o n ( H S ) For t h e p a t i e n t s h a v i n g b l o o d v o l u m e l e s s t h a n T O O m l , t h e 2 5 - m l e x c h a n g e r was d e s - i g n e d . T e s t s o f c l e a r a n c e f o r low a n d me- d i u m m o l e c u l a r mass m e t a b o l i t e s w i t h h a e - m o s o r b e n t s SCN, SCS a n d K A U s h o w e d t h e h i g h s t a b i l i t y o f c l e a r a n c e d u r i n g 2 h . o f p e r f u s i o n w i t h SCN a n d SCS. T h e same r e s u l t f o r K A U was o b t a i n e d w i t h 60-1111 e x c h a n g e r . H a e m o s o r b e n t s w e r e t e s t e d a t 3 2 0 s o r p t i o n s i n 286 i n f a n t s . For s a f e a n d e f f e c t i v e HS w e r e c o m m e n d p r e t r e a t m e n t i n c l . a u t o n o m i c b l o c k , i s o v o l a e m i a , r h e o l o g i c a n d r e s p i r a t o r y a d e q u a c y . C r i t e r i a o f HS e f f i c a c y i n c l u d e d t o x i c p r o t e i n s ( m e d i u m mass m o l e c u l e s ) , o s m o t i c h o m e o s t a s i s , p r o d u c t s o f i n c o m p l e t e o x i d a t i o n a n d f r e e r a d i c a l s i n b l o o d a n d CSF. H S w i t h m i x t u r e o f SCS a n d K A U i n o n e e x c h a n g e r or w i t h K A U a n d SCN i n t w o c o n s e c u t i v e e x c h a n g e r s i s r e c o m m e n d e d i n d e c o m p e n s a t e d m e n i n g o - c o c c a l s h o c k ; HS w i t h o x y g e n a t e d SCN - i n r e s p i r a t o r y d i s t r e s s - s y n dro ine . S t r e l k o V . , K a r t e l ' N . , T k a c h u k Z . , Medve d e v S . I n s t . G e n e r a l I n o r g , M e d i c a l I n s t . , K h a r

Chemi k o v , U


s t r y SSR

, K i e v

A NEW DRUG ZJELIVE?.Y SYSTEM FOR REGIOMAL CANCER CHEXOTHEBAAPY -BASIC STUDIES - Five d i f f e r e n t types of o n c o l y t i c d r u g s were en-

t rapped i n t o f i b r i n c l o t s , u s i n g our own n a t e r i a l , "G.T.% III", t o provide a new drug d e l i v e r y sys tem (DDS) f o r r e g i o n z l c a n c e r chemotherapy. The G. T. X i l is composed of b iodegradable g e l a t i n ( G ) , thrombin(T) and blood c o a g u l a t i o n f a c t o r XKK(XEt). The m a t e r i a l , t o g e t h e r w i t h f i b r i n o g e n , enhanced t o p i c a l accumu- l a t i o n of an i n s o l u b l e f i b r i n c l o t .

l y mixed w i t h G - T - : Z and then, r e a c t e d w i t h human Tlasma t o form o n c o l y t i c drug-containing f i b r i n c l o t s . The a n t i c a n c e r drugs used were Adr ianycin (ADM), 5-fluorouracil(5-FU), cis-platinum(cDD?) , I-litomycin C(Yu%C) and Methotrexate(KT1:). I n i n v i t r o , t h e a c t i v i t i e s of t h e drugs d e l i v e r e d from t h e f i - b r i n c l o t s were p e r i o d i c a l l y assayed . I n i n v i v o , each c l o t w i s i n t r a p e r i t o n e a l l y a d m i n i s t e r e d t o cancer (ASl30) h e a r i n g rats t o i n v e s t i g a t e t h e a n t i - n e o p l a s t i c e f 5 e c t s w i t h t h e m a t e r i a l . S o l u t i o n of each a n t i c a n c e r drug s e r v e d as t h e c o n t r o l .

c l o t s peaked on t h e f i r s t t o second day, and t h e n , g r a d u a l l y decreased f o r t h e f o l l o w i n g two weeks. S u r v i v a l terins of cancer b e a r i n g r a t s were l o n g e r chan 6 months w i t h AD::-clots, cDDF-clots and 5-FU- c l o t s . i J h i l e , t h a t %L:h t h e c o n t r o l s was w i t h i n 3 weeks a t t h e l o n g e s t . 6 e i t h e r r e c u r r e n c e of a s c i t e s n o r r e v i v a l o f mal ignant c e l l s were observed i n t h e groups t r e a t e d w i t h t h e f i b r i n c l o t s .

Gur newly d e v i s e d o n c o l y t i c DDS has a g r e a t po- t e n t i a l i n r e g i o n a l c a n c e r chemotherapy. A . SUGITACHI, i?..RIkATA, T.K:IIO, M , M T Y A . ? I , E. ShTOH, ?.IWWAHAPA and I, 8&Xf.?iOTO*. Osaka N a t l . Z o s p . , Osaka, Japan & " U n i t i k a L t d . , Kjroto, .Japan.

i n t h i s s tudy , a n t i c a n c e r drugs were i n d i v i d u a l -

A c t i v i t i e s of t h e d r u g s r e l e a s e d from t h e f i b r i n

350

352

STUDY ON PLATELET-ACTIVATING MATERIAL ACTIVATION YECHANISM BY C A T I O N I C POLYMER

A s t h e a c t i v a t e d p l a t e l e t s r e l e a s e d many growth f a c t o r s , p l a t e l e t p l a y s an impor tan t r o l e i n t i s s u e r e p a r a t i o n as w e l l as thrombus format ion . P l a t e l e t a c t i v a t i o n induced by s p e c i f i c r e a g e n t s was s t u d i e d i n d e t a i l . However t h e mechanism of non-spec i f ic a c t i v a t i o n induced by s y n t h e t i c polymer remains u n c l a r i f i e d . We examined t h e p l a t e l e t a c t i v a t i o n mechanism by c a t i o n i c polymer.

The adhes ion o f chymotrypsin-reated p l a t e l e t s t o c a t i o n i c polymer w a s same as t h a t of non-reated t r e a t e d p l a t e l e t s , s u g g e s t i n g t h a t GPIb wasn ' t r e s p o n s i b l e f o r t h e i n t e r a c t i o n between p l a t e l e t snd c a t i o n i c polymer. we r e p o r t e d t h a t t h e RGD r e c e p t o r f a m i l i e s f o r c e l l - a d h e s i v e p r o t e i n s d i d n ' t o p e r a t e i n t h e p l a t e l e t a c t i v a t i o n by c a t i o n i c polymer. I t w a s thought t h a t t h e r e c e p t o r s w e r e n ' t i m p o r t a n t t o t h e i n t e r - a c t i o n of p l a t e l e t w i t h c a t i o n i c polymer. The membrane s u r f a c e s i a l i c a c i d s played a r o l e o f adhesion s i t e of p l a t e l e t t o c a t i o n i c polymer. Furthermore t h e s i a l i c a c i d s were impor tan t t o r e l e a s e r e a c t i o n induced by c a t i o n i c polymer. Although GPIb h a s more t h a n 50% of membrane s u f a c e s i a l i c a c i d , t h e adhes ion t o c a t i o n i c polymer wasn ' t i n f l u e n c e d by t h e c leavage of GPIb. This is s u g g e s t i n g t h a t s i a l i c a c i d s r e a c t i n g wi th c a t i o n i c polymer w e r e n ' t conjugated t o t h e one g l y c o p r o t e i n .

Tadashi Suda, Takashi Takayama, and T o s h i h i r o Akaike, F a c d t y of Technology, Tokyo U n i v e r s i t y o f A g r i c u l t u r e and Technology, 2- 24-16, Nakamachi, Koganei , Tokyo 184

EXPERIMENTAL STUDY ON THE EFFECT OF LVAD ON MYOCARDIAL FUNCTION AND ORGAN BLOOD FLOW AFTER CARDIOGENIC SHOCK

i n t e r m i t t e n t o c c u l u s i o n of t h e l e f t coronary a r t e r i e s a t 37°C d u r i n g cardiopulmonary bypass . The Biomedicus c e n t r i f u g a l pump was used a s l e f t v e n t r i c u l a r assist device(LVAD). 2 9 dogs were d i v i d e d i n t o 5 groups: Group-1:Normal dogs on 1 hour LVAD(n=6). Group-1I:Cardiogenic shock, wi thout s u p p o r t ( n = 5 ) . Group-1II:Maximal i n o t r o p i c s u p p o r t group(20pg/kg /min. Dopamine)(n=6). Group-1V:LVAD s u p p o r t g roup(n=6) . Group-V:LVAD p u l s low dose i n o t r o p i c suppor t group(5ug/kg/min. Dopamine) (n=6) . I n a l l dogs, hemodynamics were measured c o n t i n u o u s l y and organ blood f low was measured by t r a c e r microspheres . Without t h e use of LVAD, 5 / 6 dogs d i e d w i t h i n 90 minutes . With t h e u s e of LVAD, s u r v i v a l improved(2/6 d i e d i n group-IV, 0/6 i n group-V). I n t h e s u r v i n g dogs c a r d i a c o u t p u t and mean a o r t i c p r e s s u r e were 80% and 73% of c o n t r o l i n group-IV, 83% and 78% i n group-V two hours a f t e r weaning from LVAD. A t t h i s i n t e r v a l b r a i n and myocard ia l blood f l o w were s t a b l e o r even i n c r e a s e d . Kidney blood f low however w a s s i g n i f i c a n t r y lower t h a n c o n t r o l ( 4 6 % i n group-IV, 53% i n group-V). These r e s u l t s i n d i c a t e t h a t LVAD combined w i t h low dose i n o t r o p i c s u p p o r t i s e f f e c t i v e i n r e s t o r i n g myocard ia l f u n c t i o n and organ blood f low a f t e r a c u t e c a r d i o g e n i c shock. Kidney f low however remains depressed .

Shungo Sukehiro, Willem Flameng Dep. of Cardiovasc. Surg. Fukuoka U n i v e r s i t y , Fukuoka, Japan . and Labo. of Experimental Card iac Sugery K.U.Leuven, Leuven, Belgium.

Acute c a r d i a c f a i l u r e was produced by


353

355

CONCENTRATION POLARIZATION AND MEMBRANE PORE BLOCKAGE D U R I N G LONG-TERM MEMBRANE PLASMAPHERESIS

We p r e v i o u s l y demonst ra ted t h e e x i s t e n c e of a c o n c e n t r a t i o n p o l a r i z a t i o n boundary l a y e r of r e d c e l l s a d j a c e n t t o t h e membrane s u r f a c e dur ing shor t - te rm ( t > 3 min) membrane p lasmapheres i s us- i n g f r e e z e - s u b s t i t u t i o n microscopy (TASAIO, 2, 510, 1987) . I n t h i s s t u d y , we extended t h e exper - iments up t o 2 h r u s i n g polypropylene (PP), polyamide (PA), and p o l y s u l f o n e (PS) hol low f i b e r s . F i l t r a t e f l u x was measured w i t h s i n g l e f i b e r s and s m a l l modules; s i n g l e f i b e r s were used f o r v i s u a l - i z a t i o n exper iments . F l u x w i t h red c e l l s ( 5 % ) s u s - pended i n e i t h e r s a l i n e o r 6% albumin s o l u t i o n de- c l i n e d r a p i d l y f o r 1-2 min and v e r y g r a d u a l l y t h e r e a f t e r i n PP and PA f i b e r s ; f l u x d e c l i n e was s lower w i t h PS f i b e r s . Switching from red c e l l s i n albumin s o l u t i o n t o albumin s o l u t i o n a l o n e d i d not i.r,crease t h e f l u x , whereas b a c k f l u s h i n g r e s t o r e d t h e i n i t i a l f l u x and subsequent r a p i d f l u x d e c l i n e h e h a v i o r . Photomicrographs r e v e a l e d a red c e l l po- l a r i z a t i o n boundary l a y e r above t h e membrane a f t e r 1 min which d i s a p p e a r e d i n PP and PA (but no t i n PS) f i b e r s i n 5-10 min, except f o r one or two layers o f c e l l s which appeared t o be s t u c k i n mem- Erane pores . Backf lush ing r e s t o r e d t h e i n i t i a l c o n c e n t r a t i o n p o l a r i z a t i o n boundary l a y e r . These r e s u l t s s u g g e s t t h a t t h e e x t e n t of pore blockage caused by deformat ion of red c e l l s i n t o membrane pores may i n c r e a s e w i t h t ime, c a u s i n g a t r a n s i t i o n from boundary l a y e r - t o membrane-l ini ted b e h a v i o r . Fhis phenomena may be a f f e c t e d by t h e pore s i z e l i s t r i b u t i o n an2 morphology of t h e s u r f a c e p o r e s . Mitsuru Suzuki , Norma J . Ofs thun , Clark K . Col ton , Dept. of Chemical Engiueer jng , Massachuse t t s I n s t i t u t e of Technologv, Cambridge, MA 02139, USA.

_ _ _ ~

BIOCOMPATIBILITY OF MEMBRANE PLASPIA SEPARATOR I N DONOR PLASMAPHRESIS

The need of plasma p r o d u c t s h a s been dramat ica l - l y i n c r e a s e d because of t h e p r e v a l e n c e of t h e r a - p e u t i c p l a s m a p h e r e s i s , b u t more t h a n 90% of plasma p r o d u c t s used was imported from o t h e r c o u n t r i e s . Doner plasmapheresis(DP) u s i n g membrane plasma separator(MPS) h a s been r e c e n t l y in t roduced t o overcome such a s i t u a t i o n . 0 n e of t h e m o s t impor tan t t h i n g s i n t h i s procedure i s t h e s a f e t y and good b iocompat ib i l i ty (BC) f o r blood donor . I n t h i s s t u d y w e performed DP w i t h 4 t y p e s of MPS i n 49 h e a l t h y blood donors and e v a l u a t e d i t from t h e a s p e c t of b iocompa t i b i l i t y . Group Module Membrane SA(m2) Type Cycle

I REF-25 T r i a c e t a t e 0.25 HF in te rm. I1 RS-P P o l y s u l f o n e 0.30 HF in te rm. 111 KPS-02 Polypropylene 0.20 HF i n t e r m . I V MS-20 Polypropylene 0 .22 Disc c o n t i n .

400-500 m l of plasma was c o l l e c t e d w i t h ACD a n t i - c o a g u l a n t i n each s e s s i o n .

Coagula t ion and f i b r i n o l y s i s t es t s showed enhanced c o a g u l a b i l i t y i n Group I1 and 1V.Moderate p l a t e l e t a c t i v a t i o n was demonstrated i n Group I and 1V.Membrane-induced complement a c t i v a t i o n was occured i n Group I and 111, b u t i t d i d n ' t a f f e c t t h e c o n d i t i o n of b lood donor c l i n i c a l l y . F u r t h e r s t u d i e s may be needed i n t h e usage of f i l t e r d plasma because i t c o n t a i n e s h i g h l y concent ra ted x t i v a t e d complement f ragments .

-~ T.Suzuki , S.Naganuma, J.Murakami, H.Arai , T.Kaneko, K.Era, Y.Kitano, M.Mineshima, T.Agishi , K.Ota Kidney C e n t e r , Tokyo Women's Medical Col lege , Tokyo, Japan

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EFFECT OF RVAD FOR R I G H T HEART FAILURE INVOLVED WITH RIGHT VENTRICULAR INFARCTION -ESPECIALLY STUDIES O F MYOCARDIAL REGIONAL BLOOD FLOW AND EPICARDIAL MAPPING ELECTROCARDIOGRAPHY

The e f f e c t of RVAD and IABP on r i g h t v e n t r i - c u l a r f a i l u r e due t o r i g h t v e n t r i c u l a r i n f a r c t i o n w a s s t u d i e d i n swine. A f t e r o r e p a r a t i o n of r i g h t v e n t r i c u l a r i n f a r c t i o n , bo?h m - A O P and CO were reduced and e l e v a t e d CVP, i n c r e a s e d RVEDP, d i l a - t a t i o n of r i g h t v e n t r i c u l a r f r e e w a l l , were noted and d iagnosed a s a c a r d i o q e n i c shock. Right vent - r i c u l a r i n f a r c t e d area w a s e v a l u a t e d by e p i c a r d i a l mapping ECG and myocardial r e g i o n a l blood f low. I t w a s found t h a t i n t h e c a s e s u s i n g IABP, t h e e f f e c t of reducing t h e i n f a r c t e d a r e a due to d i a s t o l i c augmentat ion was n o t e d , b u t t h e e f f e c t on t h e r i g h t v e n t r i c u l a r support . w a s n o t s a t i s f a c t o r y , w h i l e i n t h e c a s e s u s i n g RVAD, t h e r i g h t v e n t r i c u l a r pre- l o a d w a s reduced a n d t h e r i g h t v e n t r i c u l a r s t r o k e work was d e c r e a s e d , and t h e e f f e c t of reducing t h e i n f a r c t e d area w a s observed . But hemodynamic e f f e c t of t h e s e method were n o t s a t i s f a c t o r y . In concomi- t a n t u s e of RVAD and IABP, r e d u c t i o n of r i g h t ven- t r i c u l a r p r e l o a d and d i a s t o l i c augmenta t ion was recognized , t h e demand and supply b a l a n c e of myo- c a r d i a l oxygen was main ta ined s a t i s f a c t o r y and it w a s cons idered t h a t t h i s combinat ion mode could s u l v a g e the i schemic r i g h t v e n t r i c u l a r myocardium, and might prove e f f e c t i v e f o r t h e r e c o v e r y from c a r d i o g e n i c shock. This technique a p p e a r s t o be m o s t promising of a s s i s t i n g t h e r i g h t v e n t r i c u l a r f a i l u r e .

Osamu Suz@> ,Ta'kamitsu Hasegawa, M o t O m i Shiono, Yukihlko O r i m e , Yukiyasu S e z a i The 2nd Department o f S u r g e r y , Nihon U n i v e r s i t y , School of Medicine, Tokyo, 3apan

ADSORPTION OF ANTI-ACETY LCHOLINE RECEPTOR ANTIBODY(anti-AchR Ab) BY A NEWLY ~ l 3 W . X " P E D IMMUNOADSORBENT

W e have elsewhere reported a succesful use Of immune- adsorbent in selective adsorption of IgG, dsDNA. SsDNA in the plasma of systemic lupus erythematosus.

We, herein, report again an effect of our in Vitro use Of

immunoadsorbent on the removal of anti-AchR Ab in the plasma of myasthenia gravis(MG).

The immunoadsorbent was prepared from Sepharose CL4B and hexamethylenediisocyanate(HMD1). The beads, in the form of water swollen cross-linked gels, have the mean diameter of about 50 micron in a wet state.

The adsorption test in vitro were done as follows. Each 0.5ml of plasma from patient with MG and diabetes mellitus were mixed with 1.5mI of the wet immunoadsobent and incubated in the batch at 37C for 12Omin and thereafter the concentration of anti-AchR Ab and anti-Inslin antibody(Ab) were analysed.

Batchwise adsorption of anti-AchR Ab and anti-lnslin Ab resulted in almost complete removal of anti-AchR Ab until U P to the Prevalue of 24.0pmoI/ml and 70% reduction in the Prevalue of 2400pmol/ml, while no reduction was observed in anti-Inslin Ab.

Plasma kc, IgA and IgM levels of the patient reduced by 6% 25% and 0% respectively, indicating the possibility that anti-AchR-Ab belongs

It is suggested that the use of the immunoadsrbent may be applicabIe apply for the treatment of MG.

to IgC.

Y.Suzuki, T.Yanagisawa, H.Tsuji, K.Kuzuhara, S.Hara, Y.Ogura, O.Otsubo, T.Saino*, R.Tanioka*, K.Mita** and N.Takai**, Toranomon Hospital, Tokyo, Japan. UBE In- dustries LTD*, Tokyo, Japan. Tokyo Univ.**, Tokyo. Jauan.


3 12 ABSTRACTS OF THE VHth WORLD CONGRESS

357 ANTI-NEUTROPHIL CYTOPLASH AXTIBODIES (ANCA) IN P L A S M EXCHANGE TREATED PATIENTS WITH WEGENER'S GMSULOYATOSIS.

All patients suspected of systemic vasculitis and acute renal failure (ARF) had detected ANCA and anti-myeloperoxidase antibodies (a-MPO) by ELISA 2nd indirect '-rmmunofluorescence.Further C3d split products,circ. immune complexes and Erytrocytes CR1 levels by ELISA were studied. 14 patients with Wegener's Granuloaatosis were additionally treated with PE when ANCA had higher titer than 640 and 1 0 concrols were treated with prednisone and cyclophosphamide alone. 2 patiencs were a-KPO positive and clinically had SLE. 10 patients required dialysis, 7 in PE group. ANCA titers were monitored up to 12 mo,iths and used to control effect of PE 2nd to predict clinical relapses in every patient. They vere normalised already after 6-7 PE and in immunosup?ression group first within weeks to nonths. However all patients showed recovery of renal function and only one relapse was observed following increase of ANCA. As PE group had more severe changes in renal biopsies and hie- her se-creatinine levels we recornen6 early PE together 575th inmunosuppression in treatment: o: WG in pa:ients with ARF ;is monitorlng of SNCA in order to diagnozise, choose treatments methods and follow :he clinicai course of patients with WG.

Gladimir Szpirt, Niels Rasmussen, Bfarne Thomsen. DeTt. of Xephroiogy, Otnpathlogical Lab. and Dept. of Rheumathology, Rigshospitalet, State University Hospital, Copenhagen, Dennark.

359 I&sI(Iy AM) EXAIJBTI(1KS OP A TIJlrAL AK!XFICIAL HE74RT POR PATIRTE W r l a A S4AIUB (HEST CAVITY

Development of a total a r t i f i c i a l hear t (TAH) f i t t i n g t o patients w i t h a smaller chest cavi ty is still expected not only for bridging t o cardiac transplantation but f o r p e m e n t usage. A diaphragm-type pneumatic TAH f o r such pat ients , which is intended t o be activated w i t h electro- hydraulic actuators i n future, has been designed and evaluated in i n vi tro and animal experimnts. The basic design of the TAH is e l l i p t i c a l to u t i l i z e the craniccaudal roan of the intrathoracic space. Since the distance between the remnant si*t atria and the sternum is qui te short in h m chest, the r ight pump is designed t o be f l a t t e r than the le f t . Additionally, the i n l e t and out le t of the r ight pump is wider apart than the l e f t because the distance betwsen the r i g h t atrial and pulmnary arterial o r i f i c e is longer than t h a t betwsen the l e f t a t r i a l and the a o r t i c o r i f i c e a f t e r the resection and ta i lor ing of the natural heart. As a resu l t , the rj-ght pllmp had a f l a t t e r and longer configuration than the l e f t . In the r ight rxlmp the height was 38 m, the width was 66m and the length was 103 m, while the height was 57 m, the width was 52 mm and the length was 80 m i n the l e f t pump. The height of the connecting part of so-called "quick connectors" pssess ing the function of "valve holding rings" together was a lso decreased to 1 0 m. The cardiac output of the TAH was 8.0 L/min a t the heart r a t e of 100 bpm i n an in v i t r o evaluation. The TAH was implanted i n a ca l f of 53 kg with no s ignif icant problem and the animal is doing w e l l on the 36th postoperative day a t t h i s writing. Y-Taenaka, H. Takano, H.Noda, M.Kinoshita, A.Yagura, H.Sekii, E-Sasaki and T.Akutsu National Cardiovascular Center, Osaka, Japan

358 DIMENSIONAL CRITERIA FOR TOTALLY IMPLANTABLE ARTIFICIAL HEARTS FOR HUMAN USE

anatomical space i s a p re requ i s i t e t o decide the optimal design o f t o t a l l y implantable a r t i f i c i a l hea r t s (AH) including the s i z e and arrangement of ac tua tors . Based on the p r inc ip l e not t o compress the remnant a t r i a , which is one of t h e most important ru l e s i n AH implantation according t o l i t e r a t u r e s and au thors ' experience, computed tomographies o f magnetic resonance imaging of 4 healthy volunteers of 54-75 kg and 3 cardiomyopathy (CM) pa t i en t s of 53-61 kg were examined systematically. The chest wall and the anatomical s t ruc tu re around the hear t under physiological conditions were displayed c l ea r ly . The height of the right p a r t of t h e AH i s l imited by ( A ) : the d is tance between the sternum and the ventral edge of the a t r i a l septum, and t h a t of the l e f t pa r t i s determined by (B): the d is tance between the center of t h e mi t ra l valve and the ches t wall i n the d i r ec t ion of the apex. ( C ) : the longitudinal thorac ic length a t t he depth of a half of (A) from the sternum wi l l r e s t r i c t the cranio-cacdal dimension of the AH, and (D): the external diameter of the a t r i a a t the a t r i o v e n t r i c u l a r rings gives an idea o f the width of the AH. ( A ) was 41-55 mm, ( B ) was 70-79 mm, ( C ) was 106-150 and ( D ) was 105-118 in the hea l thy cases , and (A) was 54-62 mm, ( B ) was 81-88 mm, ( C ) was 161-171 nnn and (D) was 117-130 mm i n the CM pa t i en t s . The data above wi l l become useful dimensional c r i - t e r i a f o r t o t a l l y implantable AH f o r human use. Y.Taenaka, C.Uyama, H. Takano, H.Noda, M.Kinoshita, N.Yamada, T.Nishimura and T.Akutsu National Cardiovascular Center, Osaka, Japan

T O know the dimensions of t he ava i l ab le

360 NEW ARTIFICIAL HEART WHICH OPERATED O N THE STARL- ING'S LAW OF THE HEART

We have developed a new a r t i f i c i a l hear t ( A H ) which operated on the S t a r l i n g ' s l a w of the hear t .

T h e mechanism of our AH and experimental s tud ies in mock c i r cu la t ion and 96 dogs a r e presented.

O u r AH was constructed as follows. ( 1 ) A pa i r o f a i r -dr iven sack type pumps which

were actuated a l t e r n a t e l y was connected in para l - l e l . (2)Magnet-Hallsensor f ixed on blood chambers and housings generated e l e c t r i c a l force ,of which upper and lower l imit ,namely e l e c t r i c a l s t roke volume, were set by comparaters. E lec t r i ca l s ig - na ls from the sensors control two pumps ac tua t ing a1 t e rna te ly and au tomat ica l ly . ( 3 ) Air pressure was automatically regulated on each pumping i n the way t h a t the length of e j ec t ing time of one pump i s equal t o t h a t o f f i l l i n g time of the o ther pumg Results: ( 1 )No manual adjustment had been required

d u r i n g the e n t i r e period of s tud ie s . ( 2 ) O u t p u t changed automatically responding t o the venaus pressure. Elevating t h e venous pressure r e su l t ed i n increase i n s t roke volume w i t h increase i n both pumping r a t e and a i r pressure. ( 3 ) If the venous pressure was not changed, the o u t p u t was maintained a t a previous level by regula t ing a i r p ressure in s p i t e of changes i n the a o r t i c pressure.

ance of our AH i s cons i s t en t with the S t a r l i n g ' s law o f the hea r t .

Conc1usion:These r e s u l t s ind ica ted t h a t perform-

Hiroyuki Takagi,Akiyosi Okarnoto,Mikio Takamatu Div.research,Dept.cardiovasc.surg. Shizuoka Sa ise ika i Gen.Hosp. Shizuoka,Japan

Artficial Organs, Vol. 13. No. 4, 1989


361 NEW ANi'lCOAGULAiVi'S FOR LEFL' V W l R I C W ASS~S'I

'IIlROMBOXANE A2 SYK'LEELXE LNHIDYLQR (Om) ULVlCE (LVAU) : w7mE.Ios MEsIml'E(F-ul~ rn

'LO e s t a b i i s h an ideal xiticoagulatioii therapy, c:oritroL study was mue using n a t m s t a t mes l i a t e (LUL ) ma thromhoxarle A2 synthe tase i r lh ib i tor

) ins tcad ot h e p i r i . On 36 dogs, L V W w a s periormcu for ~4 rub ,

u i v e n by p r e m t i c pressuLe (-LUG t o +3bO nunHg). GL . i : no ariticoaguiatior1 i II=Y ) , G i . ii : h e p a r m

(I.+), G r . 1 i i : F'Vi (11=9), GL.I\/: 0i;Y ( 1 ~ 9 ) i l l a l l groups, ~4 bs' ~bA[j coulu be IJertoLmeu

with 110 thrombogeriic troubie. P,;othrombm tm (Pi') showed gradual p~olorigatiorl i n all group-.

A-EII'L. s h m u s i g n i t i c d n t prolofigatiorl alter b k k - 5

froni t he start i n G r . 1 , and earlier 111 G r . 1 1 , LLL xld 1V. Fibrir iqen showeu a s l i g h t Cleciehe t i l l I, ttrs a f t e r t h e start, but t he reo f t e r cane baci. t.v the previous leve l m G r . i i , i l l mu iV; b u t lt. showed marked decrease i n G r . i , mci reacheu

lder 50% level (below LOO mg/dl) in 24 h r ~ . -PI L J ~ S almost unchanged a l l the tm 11-1 Gc.11 Id 111; whereas it showea s i g n i f i c a n t Gecifas

Gr .i and i v , and reached 55% of p r e o p i t ; t i ~ c i I . ~ I ~4 hrs. Factor X i i showed sigriif icarit ~ L L < ~ L ~ ~ , L decrease in a1 1 groups.

1.n conclusion, no ariticoagu l a t ion iriuuces L C ~ C L E

a c t i v a t i o n of blood ccaguiation and iibrirlolysis: CIKY can keep flbsinogen w i t h l n acceptable range, bu t cannot prevent die ac t iva t ion G i riiuiiisic

pithway of bLooCi Loacjulation s y s t m . r'u: cilli

p ' even t the x t i v a t i o r i of i n t r i i , j i c pi thwdy, a i o nlaintairi the dc t iva t ion of b i d c o a p l u i m i i aia f iu r i r io lys i s a t mLnHL=i leve l .

~h.yo:~hi Onishi, Y a h i h i r o N ~ - L I x ? , I U d ~ i t F'luu,t, ',.:,uyoshl Yoshitake, 1st k p . of b u g . , bhlt;rma P l e a . C t i . , h a t m Plea. Colieye, uIiiv.oc ohy yo

.Ya~dlhlm,';&Kahrn, L.Wtue1 K;inal, PlamOrU tilrdishl,

363 COMPUTERIZED OXYGENATOR GAS EXCHANGE SYSTEM USING WEFMAL MASS FLOW CONTROLLERS

mass flow c o n t r o l l e r s (TMFCs) has been developed. System i s composed w i t h a hollow f i b e r t y p e oxygenator , t h r e e TMFCs, a medical mass spec t rometer f o r measurement of blood gas t e n s i o n , thermometers , a r o l l e r pump and p e r s o n a l computer ( E ' C ) f o r c o n t r o l and d a t a a c q u i s i t i o n . PC has f a c i l i t i e s of analogue i n p u t (A/D), analogue o u t p u t ( D / A ) and d i g i t a l o u t p u t ( D O ) i n t e r f a c e boards . S i g n a l s of blood g a s t e n s i o n of oxygen and carbon Cioxide and b lood tempera ture a r e a e u i r e d by A/D. 'I'PIFCs a r e c o n t r o l l e d by o u t p u t s of D/A and s o l e n o i d T-alves f o r s h u t t i n g p a s supply o f f are c o n t r o l l e d by DO. Not o n l y f o r t h e c l i n i c a l usage but p h y s i o l o g i c a l s tudy of c i r c u l a t i o n , mixed gas of oxygen, n i t r o g e n and carbon d i o x i d e i s s u p p l i e d t o ar~ oxygenator . System has two gas exchanqe modes: o r e i s s t e a d y f low mode and t h e o t h e r is blood g a s t .ension mode. I n l a t t e r c a s e , e s t i m a t i o n of blood 6:as t e n s i o n t o compensate e f f e c t of t h e dead t ime of t h e o u t p u t of mass spec t rometer i s c a l c u l a t e d end TMFCs are c o n t r o l l e d a u t o m a t i c a l l y . Animal Experiments u s i n g mongrel dogs have been accomplished t o confirm t h e system.

Oxygenator g a s exchange system using thermal

Makoto Takahashi , Takayuki T u j i , Kiyotaka Miwa , Akimasa I s h i d a and Kozo Suma I n s t . f o r Med. & Dent. Engng., Tokyo Medical and L e n t a l U n i v e r s i t y , Tokyo, Japan

362 EPPECTS OF P Y R I W X A L A T E D - H ~ - ? ? O L Y O X Y E T H n - ENE CONJUGATE (PEP) ON RENAL FUNClTON AND HISTOLOGY

The effect on renal function has been one of the major concerns of hemoglobin (Hb) based oxygen carriers. Preclinical assessment of the dose (1.1, 1.6, 3.0 and 5.0 gHb/kgBW) dependency effects of PHP was carried out in 8 dogs. PHP solution containing 8 g/dl of Hb was infused at 2.5 ml/kgBW/hr. In addition to blood and urine assessments, glomerular filtration rate (GFR) and renal plasma flow (RPF) were determined at 1 week pre, at immediate, 1 and 2 weeks post infusion. All dogs were sacrificed at 2 weeks post infusion for histologic examination.

Peak plasma Hb concentration achieved at the end of infusion showed dose-dependency (1.42, 1.50, 2.58 and 4.36 g/dl) as did the elevation of colloid osmotic pressure ( 4 , 4.4, 13 and 20 d g ) . A moderate reduction in GFR (max. 22%) and an increase in RPF (ranged 0-94%) post infusion were observed transiently without adverse changes in BUN, serum creatinine and electrolyte levels. Histologically. neither evidence of acute tubular necrosis nor other pathologic changes of the kidneys was observed. However, the presence of vacuoles in the proximal tubules was noted. The vacuoles stained iron-positive and were shown to contain human Hb-A. No direct relationship of the vacuoles to renal function was shown. These results indicate that the renal system tolerated well the infusions and PHP does not cause renal dysfunction in clinically considered dosages. Tsuyoshi Takahashi, Keiji Iwasaki, Paul S. Malchesky, Hiroaki Harasaki, Hideto Emoto, Michiaki Matsushita, Yukihiko Nos&, Department of Artificial Organs, The Cleveland Clinic Foundation, Cleveland, Ohio, USA.

364 STUDIES ON THE DEVELOPEMENT OF AN OPTICAL FIBER SENSOR FOR B I OCHEM I CAL ANALYS IS

For i n v i vo monitoring o f various k inds of components i n the body f l u i d , several k inds of chemical sensors have been developed mainly using electrochemical detect ion system. However, there a re components which cannot be analized by electrochemical detection. I n t h i s study, we made a fundamental research f o r the development of chemical sensors based on spectroscopic detect ion.

The sensor system consis ts o f a op t i ca l f i be r , membrane o f which spectroscopic character i s t i c s change according to the concentrat ion o f s p e c i f i c components i n a sample, and a spectrophotometer. By at taching the membrane a t the t i p of the op t i ca l f i b e r , we can measure the changes i n i t s op t i ca l proper t ies such as r e f l e c t i o n spectra.

As a prototype of these sensors, we developed a yH sensor. I n the PH sensor, pH i nd i ca to r (Thymol Blue) was immobilized i n an ion exchange membrane. By se lec t i ng appr0priat.e chromophores su i tab le f o r each pH region, the sensor can monitor the changes i n pH from 1.0 t o 13.0. Reproduc ib i l i t y i n response were a l s o observed. I t i s considered t h a t by se lec t i ng a appropr ia te reagents, var ious k inds o f sensors can be developed and tha t us ing spectroscopic information, mu1 ticomponent sensors, where reagents f o r several components are immobi 1 ized in the same membrane, can be developed. N.TAKAI', I.SAKUMA, V.FUKUI, A.KANEK0, T.FUJIE, K . TACUCH I , S . NAGAOKA * l n s t i t u e o f I ndus t r i a l Science, The Univ. of Tokyo, Tokyo, Japan

Artificial Organs, Vol. 13, No. 4, 198P

3 74 ABSTRACTS OF THE VIIth WORLD CONGRESS

365 GOVERNMENTAL CLINICAL EVALUATION OF NATIONAL CARDIOVASCULAR CENTER - TOYOBO VENTRICULAR ASSIST SYSTEM (VAS) AT THIRTY INSTITUTIONS

Sixty two VASs developed at the National Cardio- vascular Center (produced by Toyobo Co.) have been clinically evaluated to determine its reliability and effectiveness at 30 institutes. The system consists of a pneumatic diaphragm-type pump made of segmented polyether polyurethane(TM series) and a control-drive unit with an automatic flow control unit based on the automatic level control for atrial pressure and blood flow. The adult-size VAS (70 ml) was used in 56 adults and pediatric one (20 ml) in 6 children. The average duration of the use of VAS was 6.4 days (2 hours - 41 days) and average bypass flow was 4.03i1.14 l/min in adult size pump and 1.30*0.53 l/min in pediatric one. Thirty three patients (53.2%) were weaned from VAS and 14 (22.6%) were longterm survivors. Two children were weaned from VAS, but later died of IABP failure and pulmonary infarction, respectively. Thrombus formation was noted in the groove around valves in 13 cases (20.9%) and inside the pump in 2 (3.2%). Pump origin serious complications such as thromboembolism were not seen. Hema- tological and biochemical findings revealed that the VAS did not directly affect to the major organs. The control-drive unit, including the automatic bypass flow control unit, functioned accurately with less man power, securing reliable control over the circulation. A major cause of death was multiple organ failure which resulted from late application. In conclusion, the VAS has been found reliable and effective in clinical use. H.Takano, Y.Taenaka, T.Fujita, T.Akutsu, H.Manabe, R.Ornoto, S.Kyo, K.Tokunaga:Principal Investigators for NCVC-Toyobo VAS. Nat'l Cardiovasc Ctr, Saitama Medi Coll, Kyushu Univ., Japan

367 USEFULNESS O F H E P A T I C VENOUS OXYGEN SATURATION MONITORING I N PATIENTS W I T H ASSISTED CIRCULATION FOR EVALUATION OF HEPATIC PERFUSION

H e p a t i c d y s f u n c t i o n i s a ma)or c o m p l i c a t i o n p r e c l u d i n g s u c c e s s f u l c i r c u l a t o r y a s s i s t . To m o n i t o r t h e adequacy of h e p a t i c p e r f u s i o n , h e p a t i c venous oxygen s a t u r a t i o n (ShvOz) w e r e monitored i n four p a t i e n t s undergoing mechanical c i r c u l a t o r y support : t w o with IABP a f t e r coronary a r t e r y bypass g r a f t i n g , one with l e f t v e n t r i c u l a r a s s i s t d e v i c e ( L V A D ) f o r p o s t - c a r d i o t o m y c i r c u l a t o r y c o l l a p s e and one with b i v e n t r i c u l a r a s s i s t d e v i c e (BVAD) f o r a c u t e myocard i t i s . One with IABP showed markedly l o w ShvO2 v a l u e s below 30% p e r s i s t e n t l y i n s p i t e of normal mixed venous o x y g e n s a t u r a t i o n ( S v O 2 ) a n d s u b s e q u e n t l y developed h e p a t i c dysfunct ion and m u l t i p l e organ f a i l u r e . One with BVAD showed high ShvO2 v a l u e s a b o u t 80% d u r i n g t h e a s s i s t a n c e b u t d e v e l o p e d h e p a t i c f a i l u r e perhaps due t o p r i o r s e v e r e shock s t a t e . In o t h e r two, ShvO2 v a l u e s were 70% and 44% on t h e average and h e p a t i c f a i l u r e d i d not o c c u r . T h e r e w a s a s i g n i f i c a n t n e g a t i v e c o r r e l a t i o n between ShvO2 and sp lanchnic excess l a c t a t e , t h e parameter of anaerobic metabolism i n t h e s p l a n c h n i c a r e a . T h e r e was no c o r r e l a t i o n between ShvOZ and SvOz va lues below 60% i n Sv02.

The r e s u l t s i n d i c a t e t h a t inadequate h e p a t i c p e r f u s i o n r e f l e c t e d i n ShvO2 be low 30% c a u s e h e p a t i c t i s s u e hypoxia and h e p a t i c f a i l u r e . ShvO2 m o n i t o r i n g may b e u s e f u l f o r e v a l u a t i o n o f h e p a t i c p e r f u s i o n i n t h e management of c r i t i c a l p a t i e n t s r e q u i r i n g a s s i s t e d c i r c u l a t i o n . H i r o s h i Takano, H i k a r u Matsuda , Kei S a k a i , Mitunori Kaneko, Yasunaru Kawashima 1st Dept. Surgery, Osaka Univ., Dept. Cardiovasc. Surg. Sakurabashi-Watanabe Hosp., Osaka, Japan

366 IMPROVEMENT OF SURVIVAL RATE OF LVAD FOR ACUTE MYOCARDIAL INFARCTION WITH CARDIOGENIC SHOCK

Our automatic LVAD was applied in ten patients (age;52-73) with cardiogenic shock (CS) following acute myocardial infarction (AMI). Three patients were CS after AMI, two fell into cardiac arrest during coronary angiography, two went into CS after PTCA or PTCR, and three were accompanied by ventricular septa1 perforation. Three patients could not be weaned from LVAD;one due to brain damage and one due to respiratory failure. The third one who was performed three aortocoronary bypasses (ACB) 4 hours after onset of AM1 did not recover from heart failure, whose heart showed extensive hemorrhagic necrosis. Seven patients' entire circulation was well maintained at normal level during the period of 6-15 days and LVAD was successfully removed. Thromboembolism occurred in two patients whose LV cavity resulted growing thrombus. Although the natural heart did recover, two patients later died of multiple organ failure which had already developed during prolonged ischemia prior to LVAD application and one later died of recurrent heart failure. Four patients survived longer and three of them were discharged. For improvement of survival rate from CS following AMI, 1) LVAD should be applied before major organs, including heart itself, incur irreversible damage, 2) if ischemic attack does not exit, ACB should not be performed beyond 3 hours after the onset of AM1 to prevent hemorrhagic infarction, and 3) small doses of anticoagulant should be continuously administered through a small LV tube to prevent thromboembolism originated from LV. H.Takano, Y.Taenaka, H.Noda, T.Nakatani, M.Umezu, M.Kinoshita, E.Tatsumi, H.Sekii, A.Yagura, E.Sasaki, T.Fujita, T.Akutsu, H.Manabe National Cardiovascular Center, Osaka, Japan

The P l a t e l e t - S u p p r e s s i n g E f f e c t o f N e w l y 368 Designed Antithrombogenic Material

Polystyrene d e r i v a t i v e s having var ious sacchar ide groups as pendant were synthes ized . The i n t e r a c t i o n between t h e polymers and p l a t e l e t was i n v e s t i g a t e d . O u r observa t ions show t h a t t h e polymers had t h e a b i l i t y t o suppress p l a t e l e t Rdhesion and a c t i v a t i o n .

P l a t e l e t adhesion was s t u d i e d by using column m e t h o d . ( P l a t e l e t suspension was i n j e c t e d t o the column packed with t h e polymer coated beads . ) P l a t e l e t a c t i v a t i o n was s t u d i e d from the p o i n t of view of i n t r a c e l l u l a r calcium mobi l iza t ion of p l a t e l e t by u s i n g calcium analyzer . To g e t in format ions about t h e s i t u a t i o n of coated polymers , the r e l a t i o n s h i p between t h e concent ra t ion of polymer s o l u t i o n f o r c o a t i n g and t h e d e n s i t y of coated polymer w a s s tud ied by t h e modified s o l u t i o n d e p l e t i o n method. From t h e experiments t h e polymer had t h e a b i l i t y only when t h e d e n s i t y of coated polymers was high. I t may be regarded t h a t both t h e concent ra t ion and t h e conformation of t h e adsorbed polymer a r e t h e de te rmining f a c t o r s t o t h e p l a t e l e t - s u p p r e s s i n g e f f e c t .

Takashi Takayama, Tadashi Suda, Toshih i ro Akaike, Takehisa Matsuda,Kazukiyo Kobayashi, and Hiroshi Sumitomo, Facul ty of Technology, Tokyo Univers i ty of Agr icu l ture and Technology, Koganei, Tokyo, Japan; Research I n s t i t u t e , Nat iona l Cardiovascular Center , F u j i s h i r o d a i , S u i t a , Osaka, Japan; Facul ty of Agr icu l ture , Nagoya U n i v e r s i t y , Tikusa, Nagoya, Japan.

Artr$cial Organs, Vol. 13, No. 4, 1989


369 CARDIOPULMONARY BYPASS(CPB)WITH MEMBRANE OXYGENAT- OR AND CENTIFUGAL PUMP.COMPARISON WITH BUBBLE OXY- GENATOR AND ROLLER PUMP. Forty five patients(pts)were divided into the

following three groups;GroupI(15pts)underwent CPB with bubble oxygenator and roller pump,GroupII(lS pts)with membrane oxygenator and roller pump,Group 111(15pts)with membrane oxygenator and centrifugal pump.These three groups were studied from the aspects of platelet count,its functions,whole blood aggregation and intrinsic prostanoids(6ketoPG,TXB2 ) . The following results were obtained. 1.Platelet count corrected by hemodilusion decreased in GroupI and I1 within 5min of CPB,compared with that of PreCPB,but less in GroupIII. During CPB,platlet count in GroupI and I1 decreased wlth time,howe-er in GroupII1,it was well preserved. 2.Serum free hemoglobin measured by turbidmetric msthod increased with time in all three groups. But significantly less in GroupIII than other two groups at times of CPB60min.,CPB120min. and after t?e operation(p 0.05,respectively). 3.No statistical differences as to intrinsic prostanoids among these three groups were present. But serum TXB in GroupIII was less than other two g r - oups (N .S. f . These results might suggest that CPB with membrane oxygenator and centrifugal pump brings a lot of benifits on preservation of blood components,in any kinds of carddac operations,regardless of the duration of CPB. Harunori Takeda,Yoshimitsu 1shibashi.Toshikazu Ta- chiki,Hiroyoshi Matsukura,Keisuke Sakai,Tatsuzo Tanabe,Kazuo Kataoka,Satomi 0hta.Masanori Ishizaka National Hospital at Hakodate and 2nd Dep.Surg. Hokkaido University Hospital,Hakodate,Sapporo, Hokka ido, JAPAN

371 NEW ASPECT OF BIOCOMPATIBILITY OF ARTIFICIAL DIALYZER: EVALUATION BASED ON INTRACELLULAR

CALCIUM MOBILIZATION This paper presents a new aspect of artificial

dialyzer/platelet(PLT) interaction from a point view of intracellular calcium mobilization, which is the first sign of metabolic change and transmembrane signal transduction. This was assessed by incorporation of calium-sensitive fluorescent indicator(Fura-2) into PLTs.

The Fura 2-loaded PLTs suspended in serum-free buffer were passed through a minicolumn prepared from a commercially-available membrane hollow fiber. The quantitative change in free Ca ion concentration( [Ca] i) was determined from the intensity ratio between calcium-binding and c.alcium-free states of eluted PLTs. The order of elavated [Cali upon contact with dialyzer was as follows; polyacrylonitrile(PAN) E cellulose acetate(CA) >> cellulose(CEL) > ethylene vinyl alcohol copolymer(EVAL). This strongly indicates that the hydrophobic dialyzers(PAN 6 CA) significantly activated PLTs, whereas hydrophilic surface(EVAL) was the least activator. The i.ncrease in serum concentration in PLT-suspened buffer gradually reduced the elevation of [Cali. The preadsorption of proteins such as albumin, fibrinogen and fibronectin also significantly reduced the [Cali elevation.

Thus, the newly-developed method based on 1.11tracellu1ar calcium mobilization provides information on cell/material interaction at the level of transmembrane stimulation.

Yoshiaki Takemotol)”) , Takehisa Matsudal) , Eiichi Ozeki” , Taketoshi Kishimoto’) Masanobu Maekawa’) , & Tetsuzo Akutsu”. 1 ) Natl. Cardiovasc. Ctr. 2) Osaka City Univ.

370

372

PRE-DISEASED STATE MODEL OF ENDOTHELIUM DAMAGES

TRANSMEMBRANE STIMULATION OF ENDOTHELIAL CELLS INDUCED BY EXTRACORPOREAL CIRCULATION:

The extracorporeal blood circulation such as artificial dialysis activates humoral(coagu1a- tion & complement) and cellular systems. These lead to various adverse effects at local and systemic levels. One of potential systemic adverse effects is endothelium damages. In this paper, the emphasis is placed on development of pre-diseased state model as endothelial cells(ECs) are stimulated by various activated humoral factors which are generated during extracorporeal circulation.

The EC membrane stimulation was quantitatively assessed by measuring intracellular free calcium ions concentration([Ca]i), which was determined by chemiluminescence of calcium-sensitive aequorin-loaded bovine ECs. The humoral factors used as stimulants include thrombin, bradykinin, Factor Xa and complement-activated serum. The former two stimulants generate spontenious transient elevation of [Cali. The latter two exhibit irregular oscilating elevation patterns. The maximum integrated [Cali of the latter two are significantly higher than those of the former .

The intracellular calcium mobilization is the first sign of metabolic change and membrane damage. This implies that repeated stimulation by activated humoral factors as found in artificial dialysis could generate unfavorable effects to endothelium in vivo.

Yoshiaki Takernoto” ’) , Takehisa Matsuda’) , Eiichi Ozeki” , Taketoshi Kishimoto2) , Masanobu Maekawa‘) , 6 Tetsuzo Akutsu’) . 1) Natl. Cardiovasc. Ctr. 2 ) Osaka City Univ.

AN Ac(3ELERATED TEST FOR M I ~ F O ~ S OXYGENATOR (FBD) FAILURE

Ferenc Czegl N%

Yehuda T-i M e l a n i e M a Anthony J. drtolani of Shore U n i v e r s i t y H ith &set%?030 & cornell university%cal c~lle+, NY, U~A.

Arlificinl Organs, Vol. 13, N o . 4 , 1989

3 76

373

375


STUDIES FOR IMPROVEMENT OF CARDIOPULMONARY BYPASS AND OXYGENATOR FROM THE VIEWPOINT OF ANAPHYLATOXIN PRODUCTION

Complement a c t i v a t i o n dur ing cardiopulmonary bypass (CPB) was compared between a Capiox membrane oxygenator ( M O ) and a BOS bubble oxygenator (BO). Animal and i n - v i t r o s t u d i e s were a l s o performed.

I n 20 monkeys ( t h e Macaca f a s c i c u l a r i s ) sub- j e c t e d t o one-hour i n t r a a o r t i c i n f u s i o n , blood e x t r a c o r p o r e a l l y bubbled with 02 r a i s e d plasma C4a and C3a, b u t blood a f t e r c o n t a c t wi th nylon r a i s e d C3a a lone . I n i n - v i t r o s t u d i e s with human immuno- g l o b u l i n ( I g ) or albumin (Alb) denatured by O2 bubbling, denatured I g r a i s e d C4a, C 3 a and C5a i n a dose-dependent manner while denatured Alb d i d not change them.

ed wi th CPB- t ime i n t h e BO group ( B O G ) bu t l i t t l e i n t h e MO group ( M O G ) , 2 ) C3a increased l i n e a r l y i n t h e BOG b u t more s lowly i n t h e MOG, 3 ) C5a s l i g h t l y increased i n t h e BOG b u t l i t t l e i n t h e MOG, 4) such d i f f e r e n c e s tended t o i n c r e a s e w i t h t h e r a t i o of primed-homologous-blood t o c i r c u l a t - ing-autologous-blood volume, 5 ) such d i f f e r e n c e s decreased when concent ra ted r e d c e l l s ( C R C ) and Alb were primed i n s t e a d of homologous blood and 6 ) such changes i n complement l e v e l s were r e f l e c t e d on c l i n i c a l f i n d i n g s such as p o s t o p e r a t i v e pO2 e t c .

I n conclus ion , 1) t h e BO seemed t o produce complements dominantly v i a t h e c l a s s i c a l while t h e MO d i d s o v i a t h e a l t e r n a t i v e pathway; blood bubbl ing should be an important immunologic pa thogenet ic , and 2 ) CPB with CRC and Alb pr iming produced l e s s anaphglatoxin than wi th homologous blood.

In 100 p a t i e n t s undergoing CPB, 1) C4a increas-

. . - Tatsuo Tamiya, Yoshinobu Maeo, Motoshige Yamasaki, Toshiyuki Yamashiro The 2nd Dept. of Surgery, Kochi Medical School , Nankoku, Kochi P r e f e c t u r e , Japan

NCNEWASIVE KNITDlUNG OF 3FKCN 0;TIGEN i.zETABoLIS4 m T G CARDIOPU'LXINARY BYPASS BY NEAR I"ED SFJ-mmTRy. Using a near inf?cared(Pm)spectrophotometry, brain

oxygen metabolism was noninvasively studied by sinultaneous muremnt of oxygenated b g l o b h (Hb) ,reduced Hb, and total Hb content in rat and human brain in situ. Method: Tne computer-controlled spectrometer was bu i l t whereby NIR l ight from three laser diodes could be i l lmimted on the head through a fiber- optic bundle. 'Ihe transmitted or reflected light was guided into a photmultiplier operating in photon counting mde through another fiber bundle. 'Ihe change of oxygenated and total Hb content

w e r e d t o r e d using the following equations of -3 dA805f3AA830 and 1.6Ab-780 -5.8MOW.ZAA830 respecti-Jely . Results: U i t h anesthetized and ar t i f ic ia l1 ventilated rats,about go"/, of brain Hb was okygenated state a t 957D2+57LD2 in the inspired gas and 50% a t 7702+57D2,which correlated w e l l with oxygen satulation of the jguglar vein blood.

B r a i n oxygenation was continuously mnitored in the CardiopuLmXlary bypass(CPB) patients in reflectance mde. The blood w l m tended to increase during la te r phase of CPB but m s t l y returned to pre-CPB level when patient's herno- d m c s became stable after CFB discuntinued. b k g CPB the Hb oxygenation level was kept rouzhly constant at mean perfusion pressure over SGnniUg, whereas below 4hmHgthe mrkeddecrease in

Masahide Tamra , Yoshihilco - K u b , ' h r u Tarmrra, Lst Ikpt.Surg.Asahikawa Medical College,Asahikawa, Research Insti tute of Applied Electricity,Hokkaido .University, . Sapporo, Japan.

374 NEDICAL APPLICATION OF ELASTIC, PVA YYDRDGEL FOR IKPLANTAQLE MATERIAL

Thj.s PVA hydrogel . has many c h a r a c t e r s . Judging from t h e s y n t h e t i c p r o c e s s , i t c o n t a i n s no component o t h e r t h a n w a t e r and P o l - y v i n y l a1.coholfPVA). I t s water c o n t e n t i s 80 t o 90X/w resembling o r g a n i c t i s s u e . I t h a s rubber-l.i're e l - a s t i c i t y d e s p i t e t h e h i g h water c o n t e n t , and i s mechanical.1.y s t r o n g and inso1.uble i n water .

The p u r p o s e of t h i s e x a m i n a t i o n was t o confirm t h e p o s s i b i l - i t y t o apply t h i s PVA gel. .for implantab le medical. material.. I t was implanted j.n t h e r a b b i t p e r i t o n e a l c a v i t y t o s t u d y t h e changes of i t s form and s t r e n g t h i n v ivo , and t o ana tyze t h e c o n t e n t s o f t h e e l e c t r o l - y t e s absorbed i n t o t h e PVA g e l . To make a p r a c t i c a l . applYtcation, s h e e t s of t h e PVA gel. were su tured a t t h e canine p e r i c a r d i a l d e f e c t s as an an t i - adhes ive membrane.

A s t h e r e s u l t of impl-antat ion dur ing 3 m . t o 1 8 m . , t h e form o f t h e PVA gel. d i d n o t change and t h e mechanical. s t r e n g t h changed 1 i t t l . e s o t h a t t h e e l - a s t i c i t y was not l o s t . The amount of C a absorbed i n t o t h i s material. was 43.3-1013.9 PPb4 on r a b b i t and 3.91-19.40 PPM on c a n i n e . The amount of F(g was 5.45-11.9 PPM on r a b b i t and 4.97 PPM on canine .

The r e s u l t s o f t h e exaer iment a t t h e c a n h e per tcardturn reveal-ed t h a t t h e PVA d i d n o t adhere t o t h e a d j a c e n t t i s s u e and could be used as a n an t i -adhes ive membrane. Xoichi Tamura, Shigetalca Xawwarasaki, nsamu I k e , S h i g e k i S i t o m i , Jun I s o b e , Yasuhiko S h i m i a u , Tadayuki Clhnishi", Masateru Sogabe*, Tomokazu %bayashi"*, nsamu Kuwabara** ? , h e s t D i s e a s e R e s e a r c h I n s t i t u t e , K y o t o U n i v e r s i t y , Kyoto , J a p a n , +Sumibe M e d i c a l rompany Ltd . , *->alppon O i l . P.ompany Ltd .

376 PRETRANSPLANT PLASMAEXCHANGE A N D IMMUNOADSORPTION FOR H I G H L Y SENSITIZED KIDNEY TRANSPLANT RECIPIENTS

T h e n u m b e r o f s e n s i t i z e d p a t i e n t s o n t h e w a i t i n a l ists f o r r e n a l t r a n s p l a n t a t i o n i s r a p i d 1 9 i n c r e a s i n g . I n order to t r a n s p l a n t t o s e n s i t i z e d a t i e n t s a n d i m p r o v e d g r a f t p r o n o s i s , w e E a v e a p p l i e d a p r e t r a n s p l a n t p r o e o c o l o f p l a s m a e x c h a n g e , i m m u n o a d s o r o t i o n a n d i m m u n o s u p p r e s s i o n w i t h

s p l e n e c t o m y . ( 1 ) P r o t o c o l 1)Removal o f p r e f o r m e d a n t i b o d i e s

D o u b l e f i l t r a t i o n p l a s m a p h e r e s i s ( D F P P ) a n d / o r i m m u n o a d s o r p t i o n were d o n e f o r r e m o v a l o f p r e f o r m e d a n t i b o d i e s . I n b o t h m e t h o d s , p l a s m a ( 3 - 5 1 ) w a s separated b y A P - O 5 H ( A s a h i ) . E v a f l u x Z A ( k u r a r e ) w a s u s e d as s e c o n d f i l t e r i n DFPP. I M - T R ( A s a h i ) w a s u s e d a s i m m u n o a d s o r b e n t . 2 ) P r e v e n s i o n of r e s y n t h e s i s o f t h e

odies o s o o r i n ( C Y A ) 2mQ/KQ.

a n t i b C i c l

m e t h l p k e d n i s o l o n e ( M P ' ) B h g / d a y and a z a t x i o p r i n e ( A Z ) 50mg/day or m i z o r i b i n e (Mz)

50mg/day w e r e g i v e n e v e r y a f t e r h e m o d i a l y s i s ( 3 t i m e s a w e e k ) u n t i l t r a n s p l a n t a t i o n .

~ l e n e c t o m y 1) R e n a l t r a n s D l a n t a t i o n a n d SF 4) P o s t o p e r a t i t e i m m u n o s u p p r e s s i o n

a n t i q y m p h o c y t e g l o b u l i n ( A L G ) 1500mg/day(14 d a y s ) . R e s u l t s

u n d e r g o n e k i d n e t r a n s p l a n t a t i o n s u c c e s s f u l l y a f r e r o u r p r e t r a n s p l a n t r e g i m e n . D e p a r t m e n t of S u r g e r y a n d U r o l o g y , K i d n e y C e n t e r , T o k y o Women 's Medical C o l l e g e , T o k y o , J a p a n

k a z u n a r i T a n a b e , Kota T a k a h a s h i , E t s u k o A r u g a . T e t s u z o A g i s h i S a t o s h i T e r a o k a , H i r o s h i Toma, K a z u o O t a

I n d u c t i o n i m m u n o s u p p r e s s i v e d r u g s w e r e CYA 10m /Kg MP 500rng/day , A Z 1-2mg/Kg a n d

Two h i g h l y s e n s i t i z e d r e c i p i e n t s h a d

Arlificial Organs, Vol. 13, No. 4, 1989


377 HEMOSTATIC ALTERATIONS WITH VENTRICULAR ASSIST DEVICE FOR POSTCARDIOTOMY HEART FAILURE

We evaluated the hemostatic alterations in two adult patients who were supported by left ventricular assist device (LVAD) because of postcardiotomy heart failure. LVAD, using polyurethane diaphragm- atic artificial heart pump, was performed without any anticoagulant for 9 and 6 days, respectively.

and 53.Ong/ml respectively) within 3 days of LVAD. Tirombin-antithrombin IIIcomplex (TAT) became maxi- m i r n (86 and lOS?g/l) within 4 days of LVAD. There- after both parameters decreased gradually and re- timed to normal levels after weaning from LVAD. ATIII showed no remarkable change during LVAD in b3th patients but protein C (PC) decreased gradually t3 27 and 66% of initial levels, respectively, at the end of LVAD. Fibrinopeptide BB15-42 (FPBB15-42) reached peaks within 5 days of LVAD. Alpha Zplasmin inhibitor-plasmin complex (d2PI-Pm complex) also increased markedly during entire course of LVAD in both patients. However, these fibrinolytic parameters decreased immediately after the end of LVAD.

These findings indicate that for the first several days the coagulation cascade is activated, and is accompanied by fibrinolytic activation. There- after, coagulation activity is inhibited by physiologic anticoagulation consisting mainly of protein C system. Such hemostatic homeostasis works to prevent thromboembolic episodes. However, as indicated by the progressive decrease of PC level, the exhaustionof this system may lead to thromboembolic complications when the use of LVAD is prolonged.

_- TRnaka,K., Wada,K., Morimoto,T., Shomura,~., Nasu, 16.*, okada.Y.*, Yada,I.**, Yuasa,H.*f, and Kusaga- 'ua,M.*'. Toyooka Public Hospital, Kobe General I-ll,spital*, Hyogo, and Kie University**, Mie, Japan

Fibrinopeptide A (FPA) reached peak levels (39.8

379 NEWLY-DEVELOPED REGENERATED CELLULOSE DIALYSIS MEMBRANES (RCM) FOR EFFICIENT REMOVAL OF BETA-2- MICRO(rOBUL I N

B e t a - 2 - m i c r o g l o b u l i n c a u s i n g h e m o d i a l y s i s - assoc ia ted a m y l o i d o s i s i s e a s i l y removable f rom p a t i e n t s o n l o n g - t e r m h e m o d i a l y s i s b y u 1 t r a f i 1 t r a t ion. Howev er , d i a 1 y s i s t r e a t m e n t s a r e p r e f e r r e d as a me thod o f r e m o v i n g be ta -2 - m i c r o g l o b u l i n i n t e r m s o f c o s t and o p e r a t i o n . T h e p r e s e n t s t u d y e l u c i d a t e s d i f f u s i o n c h a r a c t e r i s t i c s o f new1 y - d e v e l oped r e g e n e r a t e d c e l l u l o s e membranes f o r d i a l y s i s w i t h h i g h e r p e r m e a b i l i t y t o l o w m o l e c u l a r weight p ro te ins .

D i a l y s i s exper imen ts were made a t 310K u s i n g aqueous 1251-beta-2-microgl obu l i n t o o b t a i n t h e s o l u t e p e r m e a b i l i t y o f RCM. R a d i o a c t i v i t y o f a s i n g l e h o l l o w t e s t f i b e r a f t e r e x p e r i m e n t a t i o n f o r a p r e d e t e r m i n e d p e r i o d was measured on a gamma counter. Through a n a l y s i s o f r a d i o a c t i v i t y data, t h e s o l u t e pe rmeab i l i t y was obtained, and f r o m t h i s d i f f u s i v e c l e a r a n c e (160 /500) (CL(D)) f o r be ta -2 -m ic rog lobu l i n was c a l c u l a t e d .

The RCM had a s o l u t e permeabi l i t y o f 4.38~10- Scm/s which was h i g h e r t h a n t h a t o f CT-190UI F80 and AMNeo 2001UP. and a p u r e w a t e r p e r m e a b i l i t y o f 73ml/mZ/hr/mmHg. The d i f f u s i v e c l e a r a n c e was c a l c u l a t e d t o be 41ml / m i n a t a b l o o d - s i d e f l o w r a t e o f 200ml/min (Hct:20%) and a d i a l y s a t e - s i d e f l o w r a t e o f 500ml/min.

These d a t a s u p p o r t s a t i s f a c t o r y r e m o v a l o f b e t a - 2 - m i c r o g l o b u l i n b y d i f f u s i o n u s i n g h i g h l y p e r m e a b l e d i a l y s i s membranes p r e p a r e d f r o m regenerated c e l l u l ose.

e Tats-, K i y o t a k a Saka i , J o j i N i sh i k ido* , Takuya Yamamoto*, Fumiyoshi Fushimi*, Osamu Nish ida** Dept . o f C h e m i c a l E n g i n e e r i n g , Waseda Univ . , Asahi Chemical Ind." and Asahi M e d i c a l * *

. .

378 USE OF EXTRACORPOREAL HEMOCARBOPERFUSION AND ORAL CARBON SORBENTS IN THE TREATMENT OF HEAVY METAL POISONINGS

Our experience in the treatment of acute poisonings with Hg and Pb (86 persons) gives evidence to severe clinical picture: pronounced skin ,damages of toxic and alle rgic origin (total epidermial necrosis) accompanied with failures of various organs - eyes, liver, kidneys, gastrointest inal tract etc. it is necessary to remove not only initial metallic compounds but also their metabolites in order to correct humoral homeostasis. Natural pathways for the organism detoxication through liver or kidneys or gastrointestinal tract in general are insufficient and additional active therapeutic methods have to be used. Hemoperfusion over synthetic active carbons SCN proved to be an effect ive procedure for the rapid decrease of the blood Hg level, plasma toxicity and immunosuppression. Regeneration of the sy stem and organs functions is observed. Skin is also intensively purified. Norma- lization of the arganism status is accel- erated provided nemoperfusion is supplemented with oral administration of the mi crospherical SCN beads ( G , 3 - 0 , 5 mm) in the intervals between the procedures.Chro nic poisonings with Hg and 2b are effectively treated with the SCN being administ ered per 0 s . Hg blood level dropped 6-10 times, Pb - 3-4 times after a week treat. Tarasenko Y., Mardanenko V., Novikova R., shano V., L ubianova I., Krasniuk Y.. Svi-

Donetsk, USSR ridova V. Medical Inst., Inst. General Inorg. Chem.

380 L O N G - T E R M R E S P I R A T O R Y A S S I S T A N C E U S I N G R V A D S Y S T E M A N D A M E M B R A N E O X Y G E N A T O R .

We designed a new method f o r l ong - te rm r e s p i - r a t o r y a s s i s t a n c e u s i n g a n R V A D and a membrane oxygenator (MO). An a i r - d r i v e n diaphragm t y p e RVAD was i m p l a n t e d between t h e RA and t h e P A i n 5 goats a n d a n MO was s e t o n t h e o u t l e t c o n d u i t o f t h e RVAD 2 weeks p o s t o p e r a t i v e l y . The MOs used i n t h i s s t u d y w e r e t h e S c i - M e d s i l i c o n s h e e t l u n g and a p r o t o t y p e l u n g u s i n g a nove l m u l t i l a y e r e d compos- i t e h o l l o w f i b e r membrane ( M i t s u b i s h i Rayon) i n which a v e r y t h i n po l yu re thane f i l m i s sandwiched between t w o microporous p o l y e t h y l e n e membranes so as t o p reven t serum leakage. Then r e s p i r a t o r y sup- p o r t was conducted under sys temic h e p a r i n i z a t i o n . The maximum bypass f l o w r a t e s w e r e a r o u n d 2 - 4 L / m i n (50-90 X o f t o t a l o u t p u t ) , and t h e maximum gas exchange were about 90-150 m l / m i n i n 02 t r a n s - p o r t and 70-120 m l / m i n i n C o p removal (50-90 % o f t o t a l gas exchange). S u r g i c a l b l e e d i n g o r se rum leakage d i d n o t occur i n any an ima ls f o r 4-8 days. The va lues o f plasma hemoglobin, p l a t e l e t count, f i b r i n o g e n and c l o t t i n g f a c t o r XI11 w e r e m a i n - t a i n e d w i t h i n n o r m a l range . M o d e r a t e p u l m o n a r y i n f a r c t i o n due t o i n a d e q u a t e a n t i c o a g u l a t i o n t h e r a p y was o b s e r v e d i n one case .

Th is method so l ved seve ra l problems accompanied w i t h p r o l o n g e d u s e o f M O s u c h a s s u r g i c a l b leed ing , serum leakage, d e s t r u c t i o n o f t h e b l o o d components due t o pump system, i n s u f f i c i e n t bypass f l o w , and f a t a l sys temic thrombosis . We conclude t h a t t h i s method is q u i t e s u i t a b l e f o r l ong - te rm r e s p i r a t o r y a s s i s t a n c e e s p e c i a l l y as a b r i d g e b e f o r e l u n g o r h e a r t - l u n g t r a n s p l a n t a t i o n . E.Tatsumi , H.Takano, Y.Taenaka, H.Noda, H .Sek i i , M . K i n o s h i t a , A.Yagura, E .Sasak i a n d T . A k u t s u N a t i o n a l C a r d i o v a s c u l a r C e n t e r , Osaka, JAPAN

Artificial Organs, Vol. 13, No . 4 , 1989

3 78 ABSTRACTS OF THE VIIth WORLD CONGRESS

381 APPLICATION OF A NEW EMBOLIC AND SCLEROTIC AGENT (GT-XIII) I N ENDOSCOPIC SCLEROTHERAPY

I n Japan , endoscopic s c l e r o t h e r a p y h a s been a p p l i e d i n v a r i x t r e a t m e n t , n o t on ly f o r urgent c a s e s b u t a l s o f o r p r o p h y l a c t i c c a s e s . I n t h e p r e s e n t s t u d y , we confirmed t h e h e m o s t a t i c e f f e c t s i n b l e e d i n g c a s e s a s w e l l a s improvement of v a r i - c e a l form i n a l l c a s e s by endoscopic s c l e r o t h e r a p y u s i n g G T - X I 1 1 a s an embolic and s c l e r o t i c a g e n t .

SUBJECTS: P a t i e n t s wi th b l e e d i n g caused by r u p t u r e d v a r i c e s o r wi th r i s k y v a r i c e s .

METHOD: Videoendoscope, EVG-F (Fuj inon) was used. Under d i r e c t endoscopic view, s o l formed G T - X I 1 1 (composed of g e l a t i n powder 150 mg, throm- b i n 166.7 u n i t s and F a c t o r XI11 5.2 u n i t s ) d i s - so lved i n 4 m l s a l i n e was i n j e c t e d i n t o v a r i c e s v i a 23 G s c l e r o t h e r a p y n e e d l e (Microvasive) . A hemosta t ic e f f e c t on v a r i c e a l b l e e d i n g w a s no ted i n s u b j e c t s i n whom no f u r t h e r b l e e d i n g was found w i t h i n 7 days a f t e r t r e a t m e n t . I n a l l s u b j e c t s , t h e r e s u l t s were cons idered i n terms of morpholog- i c a l changes i n t h e v a r i c e s when t h e r e d n e s s on t h e v a r i c e s d isappeared i n p r i n c i p l e .

RESULTS: A hemosta t ic e f f e c t on v a r i c e a l b l e e d i n g w a s found f o r G T - X I 1 1 i n 86% of s u b j e c t s ; e f f i c a c y based on morphological change i n v a r i c e s was 70%. Major compl ica t ions were f e v e r and c h e s t p a i n . No o t h e r s e v e r e compl ica t ions were obse rved .

CONCLUSION: Endoscopic s c l e r o t h e r a p y u s i n g GT- XIII--a new embolic and s c l e r o t i c agent - - i s a n e f f e c t i v e , s a f e and s imple method f o r v a r i x t r e a t - ment. A. Terada, E. Miyoshi, K. Yamamoto, M. Masuzawa, K . Tamura and A . S u g i t a c h i Department of Gas t roentero logy and Surgery , Osaka N a t i o n a l H o s p i t a l , Osaka, Japan

383 PZEICARDIAL H%T%ROGLV-FTS

The mechanical p r o p e r t i e s , u l t r a - s t m c t u r e end hi oc? en i c a l c onposi t i on of equel ly d i s t r i b u t e d end randomly o r i e n t e t e d s i t e s of 7 netural and I 5 g lu ta ra ldehyle - f ixed 16- t o 2 0 - week old ca lves p e r i c a r d i a l s s c s were inve s t i ge t e d . t rensmission e l e c t r o n microscopy. Uniaxial load t e s t s were done t o obta in t h e mechanicel properties.They were r e l a t e d t o t h e l i g h t and t ransmission e l e c t r o n i c microscopic appearance of t h e t i s s u e . Ib crosc opi c examina t i on revea led t h a t

pericerdium c o n s i s t s of 3 1ayers.The main of t h e f i b e r s a r e i n t h e middle of t h e s t ructure .Layers a r e conected toge ther by f i b r o b l a s t s and mesothe l ia l c e l l s wich have numerous s lender and long processes.

The col lagen f i b r e s and bundles have voluntary o r i e n t a t i o n , t h a t provides e x t e n s i b i l i t y i n a l l d i r e c t i o n s . E l a s t i c f i b r e s e r e d i s t r i b u t e d throughout t h e th ickness of t h e pericardium, t h a t provides clef o m b i l i t y .

t i o n i s an in te rmolecular cross- l inking inducing foctor.Thet orevents t h e dena-

Specimens were s t u d i e d i n l i c h t end

Study shows that glu tafs ldehyde f i x a -

tu ra t io ; of col lagen bf bioprostheses . CWTA TETERE r n s t i t u t e of Medicine. Riza. , - . Latvian SSR, USSR

382 NON-ANTICOAGULANT HEMODIALYSIS (HD) WITH ORAL ADMINISTRATION OF NEWLY-DEVELOPED ANTIPLATELET AGENT

HD without anticoagulant was successfully performed in uremic dogs only by the oral administration of newly- developed antiplatelet agent, 4-cyanc-5,S-bis (4-methoxy- phenyl)-4-pentenoic acid (E5S 10, Eisai Co. Ltd., Tokyo). In the present atudy, the effect of E5S10 on antithrombc- genecity during HD was investigated. Seven uremic mongrel dogs, orally administered 0.1 mg/kg of ESS10 1 hour before starting HD, underwent HD using hollow fiber PMMA dialyzer without any anticoagulant under the general anesthesia. Counts of blood corpuscles, hematocrit, blood chemistry, plasma TXB2, 6-keto-PGFla, PTG and PF4 were examined. The sequential plasma ESS 10 concentrations were determined by HPLC. Platelet aggregation and activated clotting time (ACT) were examined before and 1, 2, 3 and 4 hours after starting HD. In 6 out of 7 dogs, HD was successfully done with minimal clotting in drip chambers and dialyzer. Platelet aggregation rate was depressed to less than 20% throughout HD. ACT was mildly prolonged but not significantiy. Plasma ESS 10 concentration was decreased to 36.1 f 27.9 ng/ml from 123.5 k 15.3 ng/ml 4 hours after starting HD. No hemorrhagic complication was observed throughout experimental period. ESS10 seems to be prornis- sing for non-anticoagulant HD.

S. Teraoka, S. Sugiura, T. Suzuki, K. Takahashi, M. Matsuoka, K. Era, M. Mineshima, T. Sanaka, T. Agishi and K. Ota. Kidney Center, Tokyo Women's Medical College.

384 VITRo EVALUATION OF THE BIOSTABILITY OF SEG- MENTED POLYURETHANES

I n c r e a s i n g a t t e n t i o n h a s been p a i d t o t h e b i o s t a b i l i t y of segmented polyure thanes (SPU's). The o x i d a t i v e d e g r a d a t i o n of SPU is a s e r i o u s problem i n pace maker wire l e a d i n s u l a t i o n and o t h e r b iomedica l a p p l i c a t i o n s . I n t h i s s t u d y , a series of SPU's w i t h v a r i o u s p o l y o l s o f t segments w e r e p r e p a r e d and the i r o x i d a t i v e degrada- t i o n , h y d r o l y t i c d e g r a d a t i o n , and environmental s tress c r a c k i n g (ESC) were i n v e s t i g a t e d .

The SPU w i t h p o l y e t h e r sof t segment showed a l a r g e r e d u c t i o n i n s t r e n g t h i n a n o x i d a t i v e envi ronment . XPS and FT-IR measurements r e v e a l e d t h a t s c i s s i o n of p o l y e t h e r -C-0- l i n k - a g e o c c u r r s d u e t o o x i d a t i o n . The o x i d a t i v e r e s i s t a n c e of SPU was improved by the use of a hydrogenated p o l y ( b u t a d i e n e ) s o f t segment.

The h y d r o l y t i c d e g r a d a t i o n of SPU's w a s in- v e s t i g a t e d i n a p a p a i n s o l u t i o n . A h y d r o p h i l i c SPU w a s s u s c e p t i b l e t o h y d r o l y t i c d e g r a d a t i o n . XPS d a t a s u g g e s t t h a t t h e d i s s o c i a t i o n of t h e u r e t h a n e l i n k a g e o c c u r r s by enzymatic degrada- t i o n .

The envi ronmenta l stress c r a c k i n g resis- t a n c e of SPU's w a s i n v e s t i g a t e d i n a l i p i d solu- t i o n . A SPU w i t h a po ly(d imethyls i1oxane) (PDMS) s o f t segment d i s i n t e g r a t e d i n t h e l i p i d s o l u t i o n . This i s a s c r i b e d t o t h e h igh s o l u b i l - i t y of l i p i d i n t h e PDMS segment of SPU.

Atsushi Takaha a' Robert W . Hergenro ther , Ar thur J . *And S t u a r t L . Department of Chemica l Engineer ing , U n i v e r s i t y of Wisconsin, Madison, W I 53706, U.S.A,'M d t r o n i c , I n c . , Minneapol i s , MN 55434, U . S . A . 'Present a d d r e s s : Kyushu U n i v e r s i t y , Fukuoka 812, J a p a n

Cooper

Artificial Organs, Vol. 13. NO. 4, 1989


385

387

FORMING OF MULTILAYER ACXF3GATION OF ADULT RAT HEPATWJ'TES IN PRIMARY CULTURE ON ARTIFICIAL BIOMATERIAL AS ASIALCGLYWPROTEIN MODEL. Recently, cultured hepatocytes are applied to

hybrid artificial liver or hepatic biosimulator. It should be required to design a g m d substratum and to culture hepatocytes in condition of high cell density for such hepatccytes culture systems. We paid attention that hepatccyte has asialo-

glycoprotein receptors which recognize the galactose residues of asialoglycoproteins, and so synthesized lactose-callying styrene plymer which abbreviated as p\ILA. As described before, cultured hepatocytes on PVLA substratum maintained their round cell shape and expression of specific functions under the normal conditions. We found more interesting phenomenon that the

cells on PVLA substratum started gradual movement, and then remarkably formed multilayer aggregations which has long-term survival. The fonnation of multilayer aggregations clearly depended sup- plemental concentrations of growth factors such as M;F and nwnbers of seeded hepatccytes. Cclltured hepatccytes on PVLA substratum required Ca ion in order to form rnultilayer aggregations. On the other hand, formation of the aggregations was suppressed by supplementation of cis-OH-proline dosedependently. The cells in the aggregation ex- hibited better mintenance of specific functions; high ability of albumin production and bile acid synthesis than those in the monolayer culture.

may be a qoOa model for developrent of hybrid artificial liver or hepatic biosimulator. Seishiro 'Ibbe, Y u k a Takei' , Atushi M a d , Akio Yagawa, Wshihiro Akaike, Icazukiyo Kobayashi2 Fx. of Tech., Tokyo Univ. of Agric. and Tech., 1) Dtp. of Biotech., Tokyo C o l l . of Medico- Phannaco Tech., 2) Fac. of Agric., Nagoya Univ.

It seems that cell culture system described here

CRITICAL PUMP FLOW AND OXYGEN TRANSPORT: EXWCISE STUDY IN CALVES WITB NON PULSATILE BWENTRICULAR BYPASS.

To investigate critical pump flow and oxygen transport in calves with ventricular fibrillation and non pulsatile biventricular bypass, 26 exercise experiments were performed in 3 calves. Left pump flow rate was maintained at 90, 100 and 120 ml/kg/min. for 1 week each. Exercise study was performed on the treadmill with the speed increased from 0.3 to 2.1 mph. Results are shown below:

90 - 100 120 Flow Rate* - max exercise(mph) 0.3 1.1 1 . 5 0 cons%* (max EX??**) 1032 829 781

17 1 6 1 7 Sv02@(max EX"x**) % 0 extract (max Ex***) 87 86 81

2

Lacgate@@( before Ex) 10.6 0.9 0.7 Lactate (max Ex) 9.4 1.9 2.0 RAP@@@(before/max Ex) 16/18 13/20 12 /22 LAP@@@(before/max Ex) 11/16 5/12 4 /11

* ml/kg/min, ;:*0 consumption (ml/min), w:* maximum exercise, ?! mixed venous 02 saturation @@ mEq/L, @@@ mmHg.

These results suggest 1) 90 ml/kg/min of non pulsatile flow rate is the lower limit to keep calves (Ht 23-27%) alive for several days but may be insufficient for long time survival, 2 ) Oxygen could be extracted up to 85% suggest that there is no detrimental effect of non pulsatile blood flow on oxygen transport to tissue. R. Tominaga, W.A. Smith, H. Harasaki, T. Jikuya, A. Massiello, B. Wilkerson, L.A.R. Golding, Cleveland Clinic Foundation, Cleveland, Ohio USA

386 Mg BALANCE IN RENAL PATIENTS: ITS NUTRITIONAL ASPECT

Mg, one of the essential elements, is easily accumulated internally because of their deteriorated excretary renal function. The major Mg sources are from diet o r Mg containing medications, however the Mg balance for CAPD patients still remains largely unknown. We studied the relationship between Mg and other nutrients in diet, and further examined the Mg balance in CAPD patients. Mg content in diet was measured by atomic absorption spectrophotometry, K and Na by flame photometry, and Ca by fluorophotornetry. Mg levels in blood and CAPD fluids were measured by atomic absoption spectrophotometry in 10 anuric patients receiving CAPD therapy for 272 5 months. Results: Mg content in diet had a positive correlation with the content of K(r.0.915, p 0.01) , Ca(r=0.685,p 0.05) and P(r.0.755, K 0.01). But it didn't exhibit any correlation with the content of protein, Na and energy. The blood Mg levels and Mg intake levels for CAPD patients are positively correlate each other(r=0.821, p 0.01). Intake of the diet with higher Mg content caused higher blood Mg levels. showed an increase in Mg excretion levels in CAPD fluids(r=0.546, p 0.001), but blood Mg level still remained in higher range.

related to Ca, P and K content, therefore attention to the relation of Mg and other nutrition should be required in the aspect of nutrition. Furthermore, an increase of Mg intake seems to induce high blood Mg levels in CAPD patients. Yoko Toda, Masaru Umeda, Kiyoshi Tsurusaki, MasanoLu Maekawa' Dept. Hemodialysis, Tadaoka Municipal Hospital, Osaka City Univ. Med. School, Osaka, Japan

Increase in blood Mg levels

Our data showed Mg content in diet is closely

EFFECTS OF PLASMAPHERESIS ON 388 PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) BY DEXTRAN SULFATE (DS )

Many authers have reported the efficacy of plasrnapheresis in the treating patients with SLE.Recently,anti-cardiolipin antibodies were detected in SLE patients. Anti-ds DNA antibodies (A-DNA) and anti- cardiolipin antibodiesCA-CL), attracted to negatively charged ions, have been confirmed to be adsorbed by ligand,DS. In this study, we performed plasmapheresis using DS in order to establish the efficacy of the DS in removing A-CL and A-DNA from sera of SLEpatients.

performed once a week over a period of one month. In each treatment,2500ml. of separated plasma was passed through the DS. We measured A-CL,A-DNA,lynphocyte subset, ESRs,complements and other laboratory findings before, during and after treatment

This report discusses the clinical findings and changes in data after treatment with plasmapheresis using the DS.

In one series, plasmapheresis was

Masayuki Toumyou, H.Tsuda,Y.Kanai M.Yokoyama,S.Fujita, H.Hashimoto,S.Hirose Div.of rheumatology,Juntendo univ.Tokyo Japan



389 THE SAFETY OF USAGE OF THAWED AUTOLOGOUS 390 EFFECT OF O W L-THREO-3,4-DIHYDROXYPHNYLSERINE RED CELLS IN CARDIOPULMONARY BYPASS (DOPS) ON HEMODIAZYSIS INDUCED HYPOTENSION(HIH)

' h e sole way to avoid the complications of homologous blood transfusion is autotransfusion. But storing enough autologous blood for open heart surgery in the liquid s ta te is not always possible, especially in more complicated procedures. This problem is solved by storingthe blood in a frozen state. The Safety of using thawed autologous red cel ls in extracorporeal circulationCECC) has net yet been thoroughly iuvestigated. Thawed autologous red ce l l s and plasma were used for

priming the circui t of ECC in 13 cases. 'Imales, 6 f e m l e s . Aged 10 to 68yrs. average 51 yrs . The ECC time was 60 to 276 minutes and averaged 158 min., using 3 Bubble oxygenators, 10 Hollow fiber membrane oxygenators, in 4 Valve replacement Sargery, 7 aortocoronary bypass and 2 a t r ia l septa1 defect. 1. In vitro, thawed red cells showed higher osmotic

fragility compared to fresh blood. 2. The peak serum hemoglobin level, measured as a

parameter of hemolysis (168.9-flllmg/dl) showed no s ignif icant difference compared to the control group in which fresh homologous blood was used. (164*73mg/dl ) . Therefore thawed red cells can be used safely in

extracorporeal circulation for open heart surgery.

Masato Toyama, Kazuo Niwaya, Masahlro Xarakmi, Yasm Miyagi Dept. of Cardiovasc. Surg. Okinawa Kyodo Hosp. OKinawa Japan.

391 DEVELOPMENT OF MULTIFUNCTIONAL HYPERBARIC ECMO SYSTEM FOR NEONATE

Hyperbaric liquid-liquid oxygenator made of ethylene vinyl alcohol copolymer hollow fibers which are known to need small amount of heparin in use for hemodialysis ( EVAL : Kurarey Co. ) was developed. Gas exchange took place between

intracapillary (IC) venous blood and extracapillary (EC) oxygen carrier solution such as dialysate or artificial blood (FC43) while EC pressure was kept higher than IC pressure. Oxygen carrier solution was saturated with hyperbaric (up to 3.0 atm) pure oxygen. Solution shift into the blood circuit was ultrafiltrated with a dialyzer and recirculated to the reservoir for oxygen carrier solution. Oxygen transfer at the dialysate flow

rate of 400 m l in blood phase for dialysate as a carrier solution was 3.5 mllrnin at 1 atm, 7.0 ml/min at 2 atm, respectively. It was 8.3 rnl/min at 1 atm in bovine blood. Oxygen transfer increased up to 11.7 ml/min in this oxygenator. This system working not only as an

oxygenator without plasma leakage but also as a hemodialyzer is suitable for ECMO especially €or a neonate in respiratory distress associated with multiple organ failure.

H I H i s a s e r i o u s compl ica t ion i n some p a t i e n t s w i t h long term hemodia lys i s therapy(HD). Recent ly , DOPS, a s y n t h e t i c p r e c u r s o r amino a c i d of norepinephrine(NE), h a s been recognized t o be e f f e c t i v e on t h e h y p o t e n s i v e e p i s o d e of amyloid polyneuropathy o r Shy-Drager syndrome.

c a l e f f i c a c y of o r a l DOPS as a good s t r a t e g y f o r HIH i n p a t i e n t s w i t h long term HD.

DOPS(200mg) was adminis te red o r a l l y 2 h r s b e f o r e t h e i n i t i a t i o n of HD t o 1 7 p a t i e n t s w i t h HIH, and plasma c o n c e n t r a t i o n s of DOPS and NE d u r i n g HD w e r e determined. DOPS w a s e v a l u a t e d from t h e number of H I H ep isode , i n f u s i o n volume of i s o t o n i c o r h y p e r t o n i c solu- t i o n t o H I H , t h e b lood p r e s s u r e a t t h e end of HD and s u b j e c t i v e symptomes of H I H d u r i n g and a f t e r HD .

Plasma DOPS c o n c e n t r a t i o n g r a d u a l l y i n c r e a s e d d u r i n g HD. Plasma NE l e v e l d u r i n g HD w i t h DOPS w a s s i g n i f i c a n t l y h i g h e r t h a n d u r i n g HD wi thout DOPS. The number o f H I H e p i s o d e and i n f u s i o n volume d u r i n g HD w i t h DOPS were s i g n i f i c a n t l y decreased , and t h e blood p r e s s u r e a t t h e end of HD w i t h DOPS was s i g n i f i c a n t l y e l e v a t e d as compared w i t h HD w i t h o u t DOPS. d u r i n g and a f t e r HD w e r e improved i n 11 of 1 7 p a t i e n t s w i t h DOPS. Any s i d e e f f e c t of DOPS w a s n o t recognized .

e f f e c t i v e tu BIH i n l o n g term HD p a t i e n t s . Yoshiharu Tsubakihara , Takahi to I t o h , Eisaku Kitamura, Nor iyuki Okada, I s a o Nakanish i , Nobutoshi I i d a . Kidney Disease Center, Osaka P r e f e c t u r a l H o s p i t a l , Osaka, Japan

We s t u d i e d t h e pharmacokine t ics and t h e c l i n i -

C l i n i c a l e f f i c a c y of

S u b j e c t i v e symptomes

I n c o n c l u s i o n , o r a l DOPS w a s shown t o be

392 H Y D R O X Y A P A T I T E P E R C U T A N E O U S D E V I C E S IMPLANTED I N FOREARMS OF THREE VOLUNTEERS FOR FOUR YEARS

Skin interfaces are important for the transmission of energy or signals between outside and inside of the body for implanted artificial organs or sensors. The affinity of this material to the skin was studied in three volunteers. Two kinds ( A , B ) of skin buttons were

made of dense sintered hydroxyapatite. The size of types A and B were 12 mm and 1 0 m m in flange diameter, 8 mm and 5 mm in shaft height, respectively. The flange has 4 or 3 holes for suturing. One type A button was implanted in a healthy 41-year-old male in May 1 9 8 5 , and two type B buttons, one in a 42- and the other one in a 3 7 - year-old males in July 1986. The hydroxyapatite buttons implanted in

human forearms of the three subjects have been carried without any discomfort in daily life for more than 4 years, the longest implantation to date. Principally, the device has to have the flange sutured to the skin above, not to the muscle below for good movability of the button. This skin interface made of this

material can clinically be useful for driving an implanted electrodes and artificial organs.

- TakayukLTsuji, Makoto Takahashi, Kazuo Tanishita and Tatsuo Togawa, Tokyo Medical Takayuki Tsuji, Hideki Aoki, Yoshiharu and Dental University, 2 - 3 - 1 0 Kanda Shin and Tatsuo Togawa, Tokyo Medical and Surugadai Chiyoda-ku Tokyo, Japan 101 Dental University, 2-3-1 0 kandasurugadai

Chiyoda-ku Tokyo, Japan 101



393 1 L F h D L 1 I k S I S S ' r S T E . 1 : \ O U - I L V 4 S I \ F 394 B ! O O I i P R F S 5 L R E Y O i I T O R I L G C O M B I 4 O lvli H 1 I I T O Y 4 T I C I 'RI Y I N G $ 4 0 F I N I S H I 4 G

I n J a p a n , o v e r 8 , O U O p a t i e n t s w i t . h r h r o i i i c r e n a l f a i l u r e h a v e b e e n d i d l ) z ? d . I n m o s t 3 f d i a l y s i s c e n t P t s . 1 0 o r m o r e p a t i e r i t s s i n i u l r . a r i e o i i s 1 y d i a l y z e d i n o n e s h i f t . T h e r i - - f o r e , r h t i o n a l i z a t i a n a n a h i g h e r e f f i r i e i i c y o f H D s y s t e m h a v e b e e n a l w a i s r e q L i e s t e d .

h e t1a'V.e c o m p l e t e d a h i g h l y ~ f f i c i e n t , i i t d c o s t / m a n p o w e r s a v i n g s y s t e m with h m b r o . .h n o n - i n v a s i v e s p h y g n o m a n o - m e t e r w h i c h a n a l y z e s K o r o t k o f f s o u n d s h i t h a m i c r o p h o n e - t . y p e m i c r o - c o m p i i t e r i z e d a u t a m a t i c b l o o d p r e s s L i r e ( L P ) m o n i t o r h a s b e e n a d d e d to a G ; j m b r o s y s t e m . I f p a t i e n t s B P f a l l s , t h e m o n i t o r s c r e e n i m m e d i a t e l y w a r n s a t l n o r m a l i t y a t n u r s e s t a t i o n . W i t h t ! i i s B P m o n i t o r , w o r k i n g h o u r s o f a n u r s e c a n b e s a v e d p e r H D s b i f t with 4 ( 1 b ~ d s c e n t e r . E a c h p a t i e n t s B P c a n bt: i m o n i t o r e d i n d e p e n d e n t l y a t a n a d e q u a t e t i m e i n t e r v a l . M o r e o v ~ r , p i ~ t i e n t s c a r i c h e c k t h e i r o w n B P b y i m a n u a l o p e r a t i o n w h e n t h e y f e e l s i c k a n d c a l l n u r s e . T h i s s y s t e m w i t . h a u t o m a t i c p r i m i n g a n d f i n i s h i n g r I . : i c h t h e G a m b r o s y s t e m h a s , a c r . r t , a i n i n e d i c a l s t a f f ca r1 b e r e d u c e d c o m p a r e d w i t h a c o n v e n t i o n a l H D s j s t e m . N u r s e s c a n s h a r e t h e i r t i m e f o r m e n t a l c a r e o f p a t i e n t s u s i n g t h i s s y s t e m . Y II s u k e Ts ti k a m o t o_ , N om II r a , K a o r u Y o r i s h i t d , K u n i o H i r a o k a a : a n d T: 11 m i a k i M a r u rn o*; l ; , K i t a s a t o U n i v . G n m b r u m e d i c a l * : a n d T o k y o Y e d . k D t ' n t . U n i v . , Tokyo.

S S S T E H

Y II k i no r i

395 CAN HEPATOCYTES CONTRIBUTE TO AN ADVANCE OF ARTIFICIAL LIVER?

It is, unfortunately, true that no reliable artificial liver is available yet. What sort of effort can contribute to make a reliable artificial liver.

In an original attempt, we manufactured an artificial liver using approxymately 70g hepatocytes cultured on glass plates f o r the reactor of the composite mechanical liver. This artificial liver remakably prolonged the survival time of anhepatic dogs comparing with unassisted dogs. The levels of serum proteins, coagulation factors were in fair conditions, but they remained in lower levels than in which we expected.

materials f o r the hybrid type artificial liver. However, they reproduced the functions of the cells, they can reveal the functions of the liver organ insufficiently. Investigations of the precious liver structures, not as a group of cells but as an organ which controlls the cells function seem to be essential to make up an artificial liver in future.

The cultured hepatocytes is the most suitable

l'lxhihiko-Tuburaya, Junichi Uchino, Takashi KomaiQ 1 : ~ . Dept. of Surg . , Dept; of Polymer Science, Hokkaido University, Sapporo, Japan

O P T I M A L SYSTEMIC BLOOD FLOW (SBF) AND AORTIC CIIARACTERISTIC IMPEDANCE (20)

The purpose of this study was to detect the systemic blood flow demand by analyzing patterns of changes in ;lortic characteristic impedance as a basic research on the optimal control of the total artificial heart ITAH) .

blood volume change with 2 nil/& infusion OI- extraction every time from control levels, and changes of 20 were determined. Zo was constant for excessive systemic blood flows. but was increased as given flows were decreased under the control level. SHF demand was. therefore, indicated by the flexure point of a Zo-SRF curve. When SRF demand was increased using 2.4-dinitrcipl~enol , a iiietabolic stimulant. the pattern of change 111 20 for given SBF was preserved. The typical Zo-SRF relaticinship disa p pear e d when p hen to1 a m iiie , an a1 p h a sympathetic blockade, was administered. I t was confirmed that the change of Z o against SBF supply was controlled by the autonomic nervous system

Results indicate that it is possible to detect the systemic blood flow demand during 'TAH driving by the flexure point of the Zo-SBF curve irrespective of met ah olic states . Tsutsui. T., Murai. T., Ijima, H.. Mitsui. T., Hori, M. Department of Surgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba City, Japan

In iiiongrel dogs. inadequate SRF were given b y

396 ON& PIECE COMPLRlXLY R4l'JANTABI.E TOTAL ARTIFICIAL BEART (TAH) WITH A lXIN I"TRIw SEPTUM

A completely implantable TAH is under development for patients with end-stage heart failure. All necessary components are implantable except f o r a wearable battery pack. Electrical energy is transmitted transcutaneously thus eliminating a possible route for infection. The pumping unit has been optimized with respect to human anatomical fitting and hemodynamic capability.

The device is 97 mm diameter x 80 mm thick and consists of left and right pusher plate type ventricles, a double acting hydraulic actuator, and an electro-hydraulic energy converter. The actuator and its control circuit are mounted between the two ventricles in an 18 mm thick ring. It alternately engages two conically shaped pusher plates to eject the left and right ventricles. The maximum stroke length is 0.5 inch with the designed stroke volume of 64 ml. Normally, the pump is designed to be operated at 90 % of full stroke, which yields a net output of 53 ml, with valve regurgitation taken into account. The inflow and outflow ports house 26 and 22 mm ID dura mater trileaflet valves, respectively.

The blood pump resides entirely within the human intrathoracic space due to its small overall size and thin interventricular septum. Preliminary component studies demonstrate that this design can provide a flow of 6 Llmin at 110 bpm and at least 8 L/min at 150 bpm with a preload of 10 mmHg. Naoki Uchida, JiFeng Chen. Setuo Takatani, Gordon Jacobs, Hiroaki Harasaki, Steve HimleyA, Ken Butler*, Yukihiko Nos& Cleveland Clinic Foundation and "Nimbus Inc.



397 SF'ONGE PoLYuBETBANE M; FWSSIBLB EXP-AL UODEL FOR POL- BIODBGRAMTION IN VIVO

The in vivo biodegradation of polyurethane coincided with a decrease in compliance of sponge type vascular grafts. Biolized sponge and solid Biomer vascular grafts, 5 cm long, 4 nun ID and 0.5 nun wall thickness, were implanted end to end fashion as carotid substitutes in dogs for 6 weeks. Sponge graft have 35 - 50 um pore size.

Patent sponge grafts showed a decrease in mean compliance values of 13.5 to 7.14 x 10 2%/mmHg; solid grafts were unchanged at mean value of 1.0 x l o d 2 %/mmHg. Calcification within the perfusion fixed graft wall was observed histologically by Von Kossa stain and by electron microscopy. None of the solid grafts but 8 out of 9 sponge grafts showed calcification. Early crystalline formation was detected on sponge wall surfaces. Five of each type of explanted graft were analyzed by gel permeation chromatography. The elution count widths for sponge and solid grafts were significantly different, 2.33 f 0.32 and 1.99 5 0.02 (p<0.05), respectively. The widths of non-implanted grafts were 2.05 and 2.0 for sponge and solid grafts, respectively. The peak heights were not comparable due to low molecular weight contaminants.

The porous polyurethane structure shows early calcification and increases in molecular weight distribution due to its large surface area and vulnerability to mechanical stresses as early as 6 weeks. Sponge grafts serve as a model for early detection of polyurethane biodegradation. Naoki Uchida, Helen Kambic, Shun Murabayashik, Hideto Emoto, JiFeng Chen, Hiroaki Harasaki, Yukihiko Nose. Cleveland Clinic Foundation, USA. *Hokkaido Univ., JAPAN.

399 LONG TERN CLINICAL EFFECTS OF PROTEIN PERMEABLE HEMODIALVSIS (PPHD) ON THE ANEMIA I N THE PATIENTS UNDERGOING NAINTENANCE HEMODIALVSIS. To evaluate the e f f e c t and the mechanism o f

act ion o f PPHD on the anemia i n the pa t i en ts underbo i ng ma i ntenance hemod i a I ys is, ser i a! measurements o f hematocrit and other hematolo- g i c a l parameters were performed both i n PPHD group (n=15) and regular HD group (n=15). F i f t een pat ients who received PPHD had e i t h e r drug re - s i s t a n t anemia or HD amyloidosis. I n PPHD group, improvement o f anemia was recongnized i n 7 out o f 15 pat ients (47%) and blood t ransfus ion r a t e was s i g n i f i c a n t l y reduced from 0.2620.38 t o 0.08k 0.15 uni ts/month/person (p<0-05). The hematocri t rose from 22.1k3.9 t o 24.923.9 X ( ~ ~ 0 . 0 5 ) a f t e r 5 months treatment. Total p ro te in rose from 6.3k 0.6 to 6.5*0.5 g/d l ( ~ 0 . 0 5 ) . There were no s i g - n i f i c a n t changes i n the parameters of i r o n metabolism. and i n the serum leve ls o f p2-micro- g lobul in , PTH, aluminium and rrbonuclease. Seven pat ients who had e levat ions o f hematocrit i n PPHD group showed s i g n i f i c a n t r i s e s o f serum crea- t i n ine . t o t a l prote in . t o t a l catcium levels w i th concomitant decrease o f serum aluminium levels. However. there was no s i g n i f i c a n t c o r r e l a t j o n between hematocrit leve ls and serum aluminium levels. There was surface area dependent r i s e o f hematocrit i n the case of remarkable improvement o f anemia a f t e r in t roduct ion of PPHD. From these resul ts , PPHD seems t o be e f f e c t i v e t o the anemia i n the pat ients undergoing maintenance hemodia- lys is . Uremic t o x i n b ) between middle molecule range t o large molecule range might be more important ra ther than w e l l known uremic tox ins such as P2-microglobuIin. PTH and aluminium. Koshi Ueno, Ariyoshi Yatanabe,Hideo Aoyagi ,Atushi Kotoda. Keisuke Kotoda,M.D., E i j i Kusano.M.D." and Vasushi Asano.M.D." Koganei C l i n i c , ''Kidney Center, J i c h i Medical School. Tochigi, Japan

398 EFFICACY OF LARGE-VOLUME DOUBLE FILTRATION PLAS- MAPHERESIS AS ADJUNCTIVE THERAPY FOR CANCERS,

We have applied double filtration plasmapheresis (DFPP) to patients with advanced cancers to remove immunosuppressive factors (IF&) from the sera. However, conventional DFPP (CV- DFPP) combined with chemotherapy could not adequately suppress the tumor growth clinically. In this study, large-volume DFPP (LV-DFPP) in which treated plasma volume was twice (5 ,000- 6,000 ml) as much as conventional volume was applied to six cancer patients to raise the efficacy of chemoimmunotherapy. All patients had metastatic disease that was beyond surgical cure. In result, the removal rate of CEA and Ig-M by LV-DFPP was more than 85%, while that by CV-DFPP ranged from 60 to 70%. NX inhibitory activity of cancer patient's serum decreased after LV-DFPP twice more than after CV-DFPP. Inhibitory effect of sera from patients on PHA blastogenesis of normal lymphocytes after LV- DFPP was significantly decreased more than after CV-DFPP (P<0 .05) . In clinical treatment each patient's performance status remarkably improved and we have experienced that the metastatic tumor of a patient drastically regressed after LV-DFPP combined with intense chemotherapy. In conclusion, it was demonstrated that LV-DFPP was capable of removing ISFs more effectively than CV-DFPP. Therefore, this procedure combined with chemotherapeutic agents is expected to be effective as cancer therapy. Uchida-S., Sakagami,K.,Miyazaki,M.,Shiozaki,S., Fujiwara,T., Kawamura,T., Takasu,S.,Morisaki,F., Haisa,M. , Ohiwa,T. , Saito,S . , Inagaki,Y., Orita ,K. , First Department of Surgery, Okayama University Medical School, Okayama, Japan

400 ANALYTICAL STUDY ON THE PERITONEAL FLUIDS IN CAPD PATIENTS WITH DIET INDUCED CHYLOPERIRONEUM

is a rare complication in CAPD therapy, and the details remain still ambiguous. We studied on the chemical features of the peritoneal fluid in this desease by the concentrating method using ultra-filtrating membrane. from those patients undergoing chronic CAPD therapy (Duration: 65-68M) and complained of milky peritoneal fluid after taking fat rich diet without any signs of peritonitis(Group A). The results were compared to those CAPD patients with acute peritonitis(B) and those without any complications(C). The results obtained are:

Chycloperitoneum, milky chylous peritoneal fluids,

The samples were taken

A(n:4) B(n.5) C(n.5) TP(mg/dl) 167.5_+13.71 768.7+60.5# lr8.0_+24.6 Alb(mg/dl) 86.9*14.4# 107.7*40.6# 29.6i12.7 TL(mg/dl) 11.12 0.48 8.923.35 2.25 0.4 TCho(mg/dl) 2.1+0.4# 2.6*1. l b 0.2_+0.2 TG(mg/dl) 5.5k1.01 2.5i0.6C 1.4k0.2 PL(mg/dl) 3.5*0.2# 3.1*1.28 0.620.3 pP(mg/dl) 3.7&1.0# 4.022.35 0.220.2 cell components cells a few many a few #:p<O.Ol, paired t test, compared to C group TP:total proteins,Alb:albumin,TL:total lipids TCho:total cholesterol, TG:triglyceride, PL: phospholipids, @P:B lipoprotein.

Our data suggest that hyperfiltrated lipids and proteins are seen in CAPD patients with diet induced chyloperitoneum, and which causes milky peritoneal dialysates.

Masaru Umeda, Kiyoshi Tsurusaki, Yoko Toda, Nobuhide Izumi, Katsushi Mori*, Ryoji Yasumoto', Masanobu Maekawa' Dept. Hemodialysis Osaka CityUnjv. Mkd. School , Osaia, Japan

Tadaoka Vunici a1 Hospital,


401

403

ABSTRACTS OF THE

TKE .AD\~.WTAGES OF THE SPIRAL VORTEX DESIGN I N P . m W T I C BLCkjD pLT.Ips M DEPDNSTR4TED BY DYE- h?4.SHOUT TESTS. To \,erify the superior washout feature of the Spiral Vortex pneumatic pmp over conventional designs, and to further our knowledge of design factors affectirig washout, three pump chambers !A,E 6 C ) were prepared with identical dome diaphragms. Silicone o i l (viscosity: 300OcS) was niihed hsith graphite powder in a ratio of 8:l b y eight and the result painted on to the inner surfaces of Lhe housings. The pump was driven for 10 minutes in a mock circulatory system and the effects of t.he f l o w pattern examined. In A (angle between the Inlet conduit and the equatorial plane = a clocliwise continuous spiral stredine was achieved and good washout observed at the diaphragm and housing junction. The white area indicated bh- arrow X in this figure results from contact hetxeen the diaphragm and the housing. In B [inlet angle = g o o ) , the degree of washout was constant over a range of diaphragm movements. The black area indicated by arrow Y in this figure, adjacent to the inflow and outflow stream, is evidence of stasis. In type C (conventional design with inlet and outlet conduits parallel and coplanar), no flow pattern was discernible, imolring changes in stream direction during the

B C

X

?titsuo h e m , Chun-Xiu Ye, Allen H. Nugent, Victor F' . Charg . C:t Vincent's Hospital, Sydney, Australia

THREE-DIMENSIONAL MEASUREMENT OF HEART GEOMETRY FOR DESIGNING AN ARTIFICIAL HEART When an artificial heart is put into a long-term clinical use, its size should be suited to the available space of a patient and its interface should be adjusted to a remaining heart. The heart geometry is, therefore, necessary to be measured in a noninvasive way. We took 12 NMR tomographic images of the thorax, lcm apart each other, in synchronizing with the heart heat. These images were read into a computer and treated by an image processing system. The inner wall of the thorax, pericardium, endocardium of ventricles and atria, and mitral and tricuspid valves were traced by using a digitizer. These contour data were transformed into the data which can be further treated by an application software. The interface geometry of the remaining heart is; (1) the normal direction of the mitral valve plane on which the mitral valve is approximately positioned, and the size and shape of this valve, (2) the same parameters of the tricus- pld valve as in ( l ) , (3) the direction of the aortic axis and its diameter, and ( 4 ) the direction of the pulmonary artery axis and its diameter. The interface geometry, for example, of (1) is determined as follows; we rotate the heart model reconstructed by the contour data and display it on the monitor.The rotation is carried out in the way that the normal directional view cif the mitral valve can be displayed. The rotation angle between the original position and the rotated one is calculated. By repeating the similar process, the interface geometry can he measured. Chikao UYAMA and Tetsuzo AKUTSU National Cardiovascular Center Research Institute Suita-shi, Osaka, 565 JAPAN


402 THE EXTRAUTERINE INCUBATION OF GOAT FETUSES USING UMBILICAL ARTERIO-VENOUS ECMO.

We have developed a long term extrauterine Eetal incubation system using silicone hollow fiber membrane oxygenators. In order to establish the arterio-venous extracorporeal circulation (ECC), catheters were inserted into umbilical vessels of a goat fetus. The fetus was incubated in an artificial amniotic fluid container without lung respiration and the blood-gas exchange was totally sustained by the ECMO circuit. The ECMO blood flow was maintained by a specially-made contoller. Of 40 goat fetuses, we could incubate 21 until death without malfinctionings and technical errors. Among these fetuses, 11 s u r - vived for more than 100 hours, and the longest for 236 hours. During incubation, we observed various kinds of movements (gross movement, breathing movement, eye movement, swallowing etc.), and recorded multiple physiological parameters (EEG, ECG, blood pressre, CVP etc.). The depression of fetal circulatory system became obvious with the incubation time and finally resulted in fetal death. These results suggest that this system could provide a new method for the study of fetal physiology and even for the clinical use in extremely premature infants.

N. Unno, Y. Kuwabara, T. Okai, S. Kozuma, N. Shinozuka, M. Mizuno, K. Kuwana? Dept. Obst. Gynec., Fac. Med., Univ. Tokyo. Senko Medical Corp?, Tokyo, Japan.

404 RELEASE OF GRANULOCYTE ELASTASE DURING HDF: INFLUENCE OF MEMBRANE AND STERILITY OF DIALYSATE

Polysulfone (PSF) (Fresenius FBO) and Polymethylmetacrylate (PMMA)(Torray BK 1.6U) were tested in 6 patients in HDF to investigate the release of granulocyte elastase using elastase alpha1 proteinase inhibitor (EalPI) concentration as a marker (Merck; normal range = 50-100 &l) prior to ( C O ) , after 2 hours (C2) and at the end (C3) of 3 hours HDF sessions. Sterility and apyrogenicity (Limulus sensitivity = 0.12 UE/ml) of dialysate was tested at the beginning and at the end of sessions. Statistical analysis using Student's paired t- test.

N.S

BK 11 78530 )272~17113~2~21~1 230% 1 3677. Dialysate was always steri e and pyrogen-free

CONCLUSION: in HDF, using sterile and pyrogen- for all samples.

free dialysate there is no difference between PSF and PMMA in terms of biocompatibility using granulocyte elastase as a marker. At 3 hours the degree of activation is low, compared to previous studies, confirming the influence of bacterial quality of dialysate in studies of biocompatibility in extra renal therapy.

Uzan.M, Hillion.D, Haas.T, Pertuiset.N, Magde1aine.F. Beyne.P CHI Poissy and Beaujon Biochemistry laboratory Paris, FRANCE.

Artificial Organs. Vol. 13. No. 4 , 1989


405

407

IMPROVED HEMOSTASIS I N EXTRACORPOREAL CIRCULATION (ECC)

Impaired hemostas i s is a major compl ica t ion i n long-term ECC suppor t f o r c a r d i a c o r l u n g i n s u f f i c i e n c y , but i s a l s o commonly observed i n r o u t i n e cardiopulmonary bypass (CPB) f o r c a r d i a c surgery . I n a p r o s p e c t i v e p lacebo-cont ro l led double b l i n d c l i n i c a l CPB t r i a l (n=70) p e r i - o p e r a t i v e bloodlosa and blood requi rements were reduced by about h a l f with t h e use of t h e p r o t e i n a s e i n h i b i t o r a p r o t i n i n . The impaired hemostas i s i n t h e u n t r e a t e d p a t i e n t s was a s s o c i a t e d w i t h e a r l y l o s s of p l a t e l e t adhes ive (GpIb) r e c e p t o r s which were preserved by a p r o t i n i n . Addi t ion of 2.106 K I U a p r o t i n i n t o t h e pump prime was s u f f i c i e n t t o p r o t e c t t h e s e r e c e p t o r s d u r i n g t h e whole per iod of CPB. It can be concluded t h a t p r e v e n t i o n of t h e i n i t i a l p r o t e o l y t i c a t t a c k can p r e s e r v e hemostas i s d u r i n g CPB. It has t o be eva lua ted how long t h i s e f f e c t w i l l l a s t and whether i n long-term ECC repea ted doses of a p r o t i n i n w i l l be r e q u i r e d .

W.van Oeveren, M.P.Harder, L.Eijsrnan, K.J.Roozendaa1, Ch.Wildevuur. U n i v e r s i t y H o s p i t a l Groningen, The Nether lands

FACTORS INFLUENCING OPTIMAL PRO- LONGATION OF SURVIVAL OF CALVES WITH TOTAL ARTI- FICIAL HEART

Life of the bearers of total artificial heart (TAH) depends on bioengineering and physiological factors. In our experiments optimal antithrombogenic solution of TAH construction, i.e. asymmetrical diaphragm with undulating blood evacuation regimen, together with one material used for all components of TAH enabled the omitting of anticoagulation therapy. The pannus growth in the inflow ports is functional disturbance, which can be eliminated by special treatment of atrial quick connectors. The important physiological factor, lirnitating the survival is neurohormonal disturbance, which develops after the resection of biological ventricles and causes venous hypertension. This can be effectively treated, using pharmacological or electrophysiological therapy. The prevention of infection and sepsis must be performed by the increase of both specific and nonspecific resistance by appropriate treatment. By the gradual elimination of these above factors in 52 long surviving calves we could increase the survival up to 293 days. Until now we have not been able to eliminate the mineralization of driving diaphragms, which seriously threatens longer survival. The possible ways of prevention of the diaphragm mineralization are examined.

a very serious

Jaromir VaSkD, J. Petriilka , J . Cerng, M.Oostal,Z.Gregor,A.Va5kD,P.Urbinek,P.Gubs Res.C.Bio;n.Art.Cir.,PurkynE Univ., BFINO, CSSR

406 LIVER DAMAGE 114 TOTAL ARTIFICIAL HEART BEGRERS AND ITS PREVENTION

The frequent finding in the calves, surviving for several months with total artificial heart (TAH) is liver enlaigenent with typical nutmeg structure, which is characteristic for liver con- gestion. Increas-d enzyme levels (AST,ALT,GMT, LOH) and decieaszd serum aLbunin izvel is regularly observed. These chances indicate the functional liver disturbances. Liver index is regularly markedly increased. The main reason of liver pathology is venous hypertension, which develops after 50 days of pumping on the base of neurohormonal disturbance, due to the removal of biological ventricles. Antihypertensive therapy and electrical stimulation of the right atrial wall c2n decrease CVP and prevent liver changes. The liver is macroscopically normal, liver indices are decreased, and histologically most strik- ing observation is statistically significant decrease of the incidence of liver fibrosis, in comparison to the untreated group of calves. Out of all 52 long-term experiments, in 13 ca!i/es the antihypertensive treatment has been performed. In five calves with this treatment the survival times were prolonged to 218-233 days, which is undoubtedly the sequelae of the adequately performed antihypertensive therapy.

Jaromir VaSkd, S.Qole,?el: J. VaSkP1, M.OostS1, B.tlzrtmannov8, J . CErn);, P.. Va5kd Res.C.6iom.Art .Cir. ,Purkyni! Univ., BRNO, CSSR

408 U T E TJSULTS AFTER IIEj-XT V-kLVX BI OPROSTHES IS IPJl'LAXTAT I OIJ

From I971 t o 1988 I76 b i o p r o s t h e t i c h e a r t ve lves heve been implented i n t 5 e Riga Cardiac Surgery Centre.

P ive year s u r v i v a l wes 72": a f t e r b i o p r o s t h e s i s and 53,6'! a f t e r bell vPlve n r o s t h e s i s implantat ion. Lf t e r two gears 91% p a t i e n t s vfith b i o p r o s t h e s i s could be r e l a t e d t o c l a s s I ~ ~ ~ i l .

Dysfunction of b iopros theses was encountered i n 9,25 of t h e p a t i e n t s .

Low frequenc:f of c a l c i f i c a t i o n can be l inked with a w-edominant use of xenoper icerd ia l b iopros theses a n d pemanent an t icoagulant ( I; vitsmir. an tagonis t s ) therapy.

Inst;. of ::edicine, Ri t?2 , Latvien SS?.,USSR

Artificial Organs, Voi. 13, No. 4, 1989

ABSTRACTS OF THE Vllth WORLD CONGRESS

CO (l/min)

control 1.5

385

Hb t rans conswrp t rans c o n s F

13.1 267 42 - - (g/dl) (ml/min) (ml/min)

409

411

a f t e r bleeding 0.9

E C A L U A T l O k OF BLOOD CONTACTING SURFACE OF SHANGHAI ARTIFICIAL VEYTRICLES VITH SCANVING ELECTROL 4IC4OSCOPY (SEY)

>f inner sur face of Shanghai pneumatic a r t i f i c i a l i e n t r i c l e s and thrombosis on the blood contac t ing s u r f a c e , e ight pre-postimplanted a r t i f i c i a l ven- t r i c l e s vere observed and evaluated w i t h SEY. The v e n t r i c l e s were made of Pe l le thane 2363-8OA & PL-BD (made i n China) r e s p e c t i v e l y , w i t h d ip-coat ing process . The i n vivo test ventricles were implanted 6-25 d3ys. About LO SEX samples (4x5 mm) vere taken from t h e inner sur face of every v e n t r i c l e , and pro- ct?ssed € o r SE3 examination. The sur face morphology and depos i t ion vere observed i n d e t a i l s . I n t h e observa t ion , Four k i n d s of sur face d e f e c t s were seen on the sur face of v e n t r i c l e s -- a i r bubble c r a t e r , open bubble, contaminated d u s t , and g e l p a r t i c l e . The i n vivo r e s u l t s shoved t h a t t h e throm- b u s formation on the blood contac t ing sur face vas assoc ia ted k i t h these d e f e c t s . The new v e n t r i c l e improved i n process and q u a l i t y c o n t r o l shoved a smooth surfaco. 90 s u r f a c e d e f e c t s and v i s i b l e thrombus was found i n t h e v e n t r i c l e w h i c h was implanted 16 days. O n l y some gross ly i n v i s i b l e f i b r i n o u s depos i t ion was noted on t h e sur face near DHJ.The results i n d i c a t e t h a t t h e appropr ia te pro- c e s s and q u a l i t y c o n t r o l of c a s t i n g sur face a r e very s i g n i f i c a n t f o r l i m i t i n g t h e sur face d e f e c t s and f o r developing a s a t i s f a c t o r y a r t i f i c i a l ventricle v i t h remarkable ant i thrombogenici ty . Weakly s i g n i f i - (cant deferance i n s u r f a c e d e f e c t s between tvo k i n d s of polyurethane sur face was noted.

H.S. Wang, Y . A . J i n . and J.N. Q i n , Lab. of A r t i f i c i a l Heart , Shanghai Second Medical U n i v e r s i t y , Shanghai, China

I n o rder t o understand the microscopic morphology

11.1 139 40 - -

THE KELATIQNSHIP AMONG COMPOSITION, MICHO- STRUCTURE AND BLOOD COMPATIBILITY OF BLENDED I'OLYETIIER-POLYESTER BLOCK COPOLYMER

A series o f blended p o l y e t h e r - p o l y e s t e r b lock copolymer (BPI%) wi th d i f f e r e n t h y d r o p h i l i c i t y / hydrophobic i ty h a s been p r e p a r a t e d by b lending of t w o k i n d s o f p o l y e t h e r - p o l y e s t e r block copolymer (PEGT-PET and PTMCT-PET), which one c o n s i s t s o f po ly(e thy1ene g l y c o l ) - t e r e p h t h a l a t e (PECT) as a h y d r o p h i l i c s o f t segment and p o l y e t h y l e n e t e r e - p h t h a l a t e (PET) as h a r d segment, and another one c o n s i s t s of p o l y ( t e t r a m e t h y 1 e n e g l y c o l ) te reph- thalate (PTMGT) as a r e l a t i v e l y hydrophobic sof t segment and a l s o PET as a hard one. The r e l a - t i o n s h i p among composi t ion , microphase-separated s t r u c t u r e , s u r f a c e p r o p e r t y and blood compatibi- l i t y o f BPEE h a s been s t u d i e d by means of U S , VES, DSC, SEM, TEM and by measuring o f p l a t e l e t s o r p t i o n and r e c a l c i f i c a t i o n time. I t was found t h a t : improvement o f b lood c o m p a t i b i l i t y o f poly- e t h e r - p o l y e s t e r b lock copolymer can be achieved by a b lending technique. r a t i o o f PTMGT-PET t o PEGT-PET (60 t o 40) , t h e blended copolymer (BPEE @/LO) shows t h e b e s t blood c o m p a t i b i l i t y , as well as ' s p e c i f i c microphase-separa ted s t r u c t u r e and s u r f a c e proper ty . The r e s u l t s show t h a t t h e blood c o m p a t i b i l i t y o f a polymer i s s t r o n g l y i n f l u e n c e d by s u r f a c e pro- p e r t y , microphase-separated s t r u c t u r e and hydro- j i h i l i c / hydrophobic ba lance o f t h e material. polymer which h o p e f u l l y t o be used as a blood compat ib le material has been suggested.

Under a s p e c i f i c molar

A

Shenguo WANC, Xuefen LI, ' lucai KE, Chuanfu CHEN, Z h i f e n LI I n s t i t u t e of Chemistry, Academia S i n i c a B e i j i n g 100080, China

410

412

DEVELOPXENT d3D IXVESTIGATION OF SHAkGHAI PVELYATIC

4 new improved pneumatic a r t i f i c i a l v e n t r i c l e has been developed i n Shanghai. Tvo s i z e s of t h e v e n t r i c l e were designed f o r l e f t v e n t r i c u l a r a s s i s t d e v i c e used i n a d u l t s (50 ml) and c h i l d r e n (30 mi). The v e n t r i c l e vas maae o f Pe l le tnane 2363-8OA b y dip-coat ing process. The housing p i t h an in tegra ted diaphragm formed a seamless sur face i n s i d e blood chamber. Reasonable cas t ing technique and s t r i n g e n t q u a l i t y c o n t r o l vere car r ied O U L i i i the process. T h e chronic ant i thromboaenici ty of 50 m l v e n t r i c l e s i n vivo was inves t iga ted macro-microscopically, Four v e n t r i c l e s were implanted i n th rce ca lves v n i c h s u r - vived 16-31 days, for l e f t v e n t r i c u l a r bypass. Pump- i n g aurar ion ranRed 6 - 2 5 days (mean 13.7 days) . By- pass r a t e was 2.0-2.5 L / m i n . Appropriate heparin vas adminis tered during-postopernt ion.

pec ia l ly around DHJ. ana some s u r f x e defec ts were iound on t h e inner s u r i a c e under thrombus. i n the e a r l y developed v i n r r i c l e s . Bu t thc n e v develoPod v e n t r i c l e had the best ant i thromboaenici ty , and i t s inner s u r f a c e was f r e e from thrombus grossly ano d e f e c t s microscopical ly . O n l y a l i t t l e grossly i n - v i s i b l e f i b r i n o u s layer was seen a t DHJ w i t h SEM. Cer t ian degree thrombus was a l s o noted a t t h e disc valves both i n l e t and o u t l e t . T h e r e s u l t s i n d i c a t e t h a t t h e new improved v e n t r i c l e can surpport cir- c u l a t i o n f o r chronic v e n t r i c u l a r bypass w i t h m i n i m u m thrombus formation. The 30 m i v e n t r i c l e f o r c h i l d r e n has been inves t iga ted i n v i t r o and i t s i n vivo t e s t i s being prepared. H.S. bang, J.N. Q i n , Y . A . J i n , Z .Y. D i n g , W . X . D i n g , and X.C. Lan Inst. of Biomed. Engr.,, Shanghai Second Medical Universi ty , Shanghai, China

A R T I S I C I h L VEYTRICLES

%me thrombi were noted i n the blooo cnamoer es-

IN VIVO EXALUATION OF OXYGEN CARRYING CAPACITY OF CCTPIEELY ARTIFICIAZ. LIPOSOMEHEME (L/H) The authors produced rompletely a r t i f i c i a l oxygen

carrying substance by enbedding synthesized hem i n liposm. Oxygen carrying capacity of this substance in vivo w a s evaluated i n dogs.

[Method] Under control vent i la t ion, 27ml/Kg of blood f r m dogs weighning 8.0 to 11.0 Kg w a s shed. Cardiac output (a), hemoglobin concentration (Hb) OLtransport, Olconsumption, before (control) and after bleeding were obtained. Then 27rnl/Kg of L B solutions was intravenously injected. S a n ~ parameters shown above were obtained. Oltransport by and O ~ c o n s q t i o n frcm liposclmeheme =re a l s o measured.

[Result] Result in a representative dog weighning 11 Kg w a s sham helm.

[Conclusion] One th i rd of oxygen consmed by the dog w a s from oxygen transported by Lfi. Thus this L/H has ability to bind and transport oxygen t o

I) the t issue. ,I Masazumi Watanabe, Koichi Kobayashi, Tsuneo Ishihara? Masanori FukuzuniL! Hiroyuki Nishide? Eisyun Tsuchida Y Keio University;) Waseda University:) Tokyo, Japan

Artificial Organs, Vol. IS, No. 4, 1989


413 EXTRACORPOREAL REMOVAL OF ANTI-HLA ANTIBODIES I N TRANSPLANT CANDIDATES WITH THE DUPONT ANTIBODY REMOVAL SYSTEM: RESULTS OF A PHASE I STUDY.

r e n a l t r a n s p l a n t a t i o n possess c i r c u l a t i n g a n t i - bodies t o HLA a n t i g e n s p r e s e n t on more than 50% of p o t e n t i a l donor k idneys . W e r e p o r t t h e r e s u l t s of an e i g h t e e n month s t u d y i n which f o u r - t e e n s u b j e c t s were t r e a t e d w i t h an e x t r a c o r p o r e a l immunoadsorption system (Immunosorba@/Citem 108) t h a t s e l e c t i v e l y removes immunoglobulin from plasma. P a t i e n t s were t r e a t e d a v a r i a b l e number of t i m e s and t h e e f f i c a c y of t h e p r o c e d u r e s , t h e dynamics of anti-HLA a n t i b o d y removal and r e - e q u i l i b r a t i o n , as w e l l as t h e c l i n i c a l s a f e t y of t h e procedure were a s s e s s e d . Plasma IgG l e v e l s were reduced by 90% i 8% of c o n t r o l v a l u e s (P<O.Ol), whi le albumin l e v e l s w e r e reduced by only 11% (PC0.05). S p e c i f i c c y t o t o x i c anti-HLA ant ibody t i t e r s were reduced s i x t e e n - f o l d and % panel r e a c t i v i t y (PRA) w a s lowered on average by 3 4 % . During t h e four week follow-up p e r i o d a n t i - HLA ant ibody t i ters and % PRA r e t u r n e d t o b a s e l i n e l e v e l s , imply ing t h a t t h e r e w a s no s i g n i f i c a n t rebound e f f e c t of t h e procedure i n t h e s e p a t i e n t s . There w e r e no remarkable changes observed i n blood c h e m i s t r i e s nor w e r e t h e r e any u n a n t i c i - pated a d v e r s e r e a c t i o n s s e e n i n t he p a t i e n t s t r e a t e d . S e l e c t i v e e x t r a c o r p o r e a l immunoadsorp- t i o n i s an e f f i c i e n t and s a f e way of removing IgG anti-HLA a n t i b o d i e s and, i f s u s t a i n e d by immunosuppression, may i n c r e a s e t h e l i k e l i h o o d of s u c c e s s f u l t r a n s p l a n t a t i o n i n t h i s p a t i e n t popula t ion .

Approximately one-half of i n d i v i d u a l s a w a i t i n g

R. M. Watt', E. A . M i l f o r d * , and R . M. Hakin? I C e n t r a l Res. 6 Dev. D e p t . , D u P o n t , Glenolden , PA, U S A , 'Renal Div. , Brigham & Women's H o s p i t a l , Boston, MA, 3Vanderb i l t Univ. , N a s h v i l l e , TN.

415 PARATHYROID HORMONE (PTH) AND OSTEOCALCIN LEVELS IN SERUM AND ULTRAFILTRATE (UF) DURING HEMOFILTRATION (HF)

HF has been claimed to have beneficial effects in preventing dialysis-associated bone disease as compared to hemodialysis. Previous SIU- dies during HF have shown removal of F'TH. mostly with analytical methods that Cannot separate intact PTH from its fragmenls. We have therefore measured bolh intact PTH (1-84) and Mid-C regional PTH (44-68). We also analyzed the behavior of osteocalcin during hemofilwtion.

Sevenwen patients on chronic HF Ueatment were studied during one session of HF. HF was performed using a polyacrylonitrile filter (PAN 250). Intact PTH was measured with an immunoradiometric assay. Mid-C PTH and osteocalcin were analyzed by competitive RIA.

Results Intact PTH Mid-C PTH Osteocalcin

Before 3u)lt215 ng/l 3740-12780 n u 19.1t7.8 bg/l After 176il20ng/li 212W1920 ngll 16.1k6.7 p@* Amount in UF 348k68 ng 20.6k17.6 Bg 12&78 pg 'pc0.01 compared pre with post HF values

S-calcium increased significantly during HF-treatment, and there was a significant correlation between the increase in S-calcium and the decrease in intact FTH in serum (pc0.05).

Conclusion: During HF there is a decrease in serum of intact PTH, Mid-C regional PTH and osteocalcin. The reduction of circulating intact PTH is pmly related to the loss of peptide during HF. Another factor seems to be a direct inhibition of secretion due u) an increase in S-calcium during the procedure.

Lars G Weiss, Bo G Danielson, B j h Wikstrih. Sverkcr Ljunghall Dept of Internal Medicine, University Hospital, Uppsa1.i. Swedcn

414 EFFECT OF FLUOSOL-@ ON 51CR-SHEEP RED CELL CLEARANCE IN THE RAT IN VlVO AND IN THE ISOLATED PERFUSED LIVER. The impact of perfluorochemical emulsions on the Reticuloendothelial System (RES) is unclear. We measured the effect of Fluosol-Oon RES clearance of 51 Cr-labelled heat denatured sheep red blood cells (51Cr-SRBC) in the rat in vivo and also in the isolated perfused liver (IPL). Rats (240-350 gm) were injected i.v. with low doses of FluosolQ (2ml/lOO grn bw) for 4 days. Controls were untreated or injected with the Fluosol-a minus the perfluorochemicals. On days 4 and 16, in vivo or IPL experiments were performed. Clearance showed first order kinetics during the first ten minutes in vivo and in IPL. Clearance constants (k) were calculated using A=Aoe-kt. The capacity of the whole liver for phagocytosis was measured by A U C ~ O . In controls the IPL cleared at the same rate and the same amounts as in vivo validating the use of the IPL model. Our data show that although Kupffer cell function is impaired in FluosolJ8 treated rats as demonstrated in the IPL model, the RES functions normally in vivo.

4 !& [6a 1 c o n " i r , 16 day c o n r l t o in vivo -.04 -.029 2932 3300 2932

+.02(7) &.006(4 +.01(5) +224 +lo7 +428

&.01(4) +.005(6) .007(4 +492 5179 k89 IPL -.03 -.017' -.019 3261 3790' 4251'

"mean +SD(n), 'pc.05

Weinstock. Shellev B. and Betensky, Hannah T. Barnard College, Columbia University New York, NY. 10027 USA

416 LDL REBOUND dpTw LDL ApHERgsIS: DATA ANALYSIS USING M A m T I C A L MODELS

S i x h y p e r l i p i d e m i c p a t i e n t s ( p r e t r e a t m e n t t o t a l c h o l e s t e r o l 326-441 mg/dl) and 5 v o l u n t e e r s ( p r e t r e a t m e n t 165-277 mg/dl) were t r e a t e d by t h e r m o f i l t r a t i o n 1 4 and 5 t i m e s r e s p e c t i v e l y . P o s t t r e a t m e n t plasma LDL c h o l e s t e r o l (LDLc) rebound w a s measured and ana lyzed u s i n g one plasma compartment (OC) and two compartment (TC), plasma LDLc and l i v e r t o t a l c h o l e s t e r o l , models. I n TC model c h o l e s t e r o l u p t a k e by t h e l i v e r is d e s c r i b e d by r e c e p t o r independent and r e c e p t o r media ted t r a n s p o r t . OC model a n a l y s i s of p a t i e n t d a t a r e s u l t e d i n the low a v e r a g e LDLc f r a - y i o n a l c a t a b o l i c rate (FCR) of 0.15 f 0.06 day . I n c o n t r a s t , t h e TC model c a l c u l q e d t h e p r e t r e a t - ment FCR f o r LDLc as 0.19-lday and the maximum FCR f o r LDLc of 0 .26 day on t h e 4 t h day. TC model showed t h a t i n p a t i e n t s and v o l u n t e e r s t h e p o s t t r e a t m e n t LDL synthesis rate rose by 6% t o 15%. OC model p r o v i d e s a c l i n i c a l l y u s e f u l method f o r c a l c u l a t i o n of t h e a p p a r e n t (combined measure of LDL s y n t h e s i s and removal) FCR f o r LDLc. TC model p r o v i d e s a b e t t e r d e s c r i p t i o n of t h e p h y s i o l o g i c a l mechanisms of LDL c o n t r o l .

Andrzej Werynski, P a u l S . Malchesky, Yukihiko Nos&, The Cleve land C l i n i c Foundat ion, Cleveland, Ohio, USA.

Artificial Organs, Vd. 13, No. 4, 1989

ABSTRACTS OF THE

417 C. I . M . FOR IMPLANTS. HIGH SPECIFITY BIOMATERIALS DESIGNING, ENGINEERING AND PRODUCTION FOR INDI- VIDUAL IMPLANTS BY ALL LEVEL COMPUTER INTEGRATION.

Computer integrated manufacturing (CIM) as currently worked out for increasing specifity, quality and economy in industrial high technology products, has utmost interesting components to be mdified for and applied to individual implant designing, engineering, manufacturing and bio- testing of the biomaterial and of the finished iqplant. As a fundamental research programme for orthopedic implants CIM-components, i.e. CAD, CAP, CAM (CADAM. CATIA and CAEDS running on IBM 3090 host: five axis machining center) have been specified for creating individual hip endoprostheses with a new anisotropic thermoplastic fibre compound biomaterial in order to highly meet individual requirements of a patient. CAQ and qualifica- tion of the biomaterial was achieved through computer controlled scanning electron and light microscopy image analysis (TN 8500). The study shows that reproducable results of fully formfit total hip endoprostheses stems with qualified fibre reinforced thermoplastics can be achieved by hichly integrated application of computer assist techniques.

Results of individually desiqninq. enqineerlng ranufacturing and quality controlling inciuding

~

computer assisted biocompatibility testing will be presented. P. ncar-future lay-out for on-line producing of individual orthopedic implants by complete computer integration of medical and technical data will be drawn. Erich Wintermantel Swiss Federal Institute of Technology, Irstitute for Designing and Build-up Technologies. t G D 52.1, Ramistr. 101. CH-8092 Zurich, Suisse

419 : ? i C T W C HYPERTENSION WITH HISTOLCGIC4L CHANGES ?OLLGWING PRoLrlNGEE LVAD INSERTION IN CALVES

Implantable left ventricular assist devices (LVADS) are being developed for long term cardiac siipport. we have studied the hadynamic effects (of an implanted pusher plate LVAD utilising LV apical cannulation in calves. Hadynamic wxiairements were m d e before, and at regxilar inteivals following device insertion. By the seventh week we have observed a significant rise in b t h systolic(SBP) and diastolic (DBP) b ! d aressures. The observed rise in 'cardiac output (CO) did not reach statistical sicmificance.

CONTROL 7 WEEKS 5BRm-W mean (SD) 125.5 ( 1 9 . 6 ) 165 ( 2 9 . 4 ) * 3BF?1unHi mean (SD) 63.5 (25 .2 ) 97 ( 2 2 . 4 ) ' '30 l/min (SD) 8.4 ( 2 . 5 ) 11.4(2.1)

n = 4 *p ( 0 . 0 0 5

The histological findings of renal arteriolar medial hypertrophy and intiml hyperplasia present at post mxtem in all these animls is consistent with a significant degree 'of systemic hypertension. The developing 'Iypertansion must Ge taken into account when ??nsirlering the long term use of these devices. F x s i b l e mechanisms include prolonged increase in c3rdisc Output, well preserved native LV fa-ct ion or a1 tered neuro-hmral control systems 2~ i cnnsequence of the LVAD mintaining .b : :nrmll : , icw left atrial and LV intra-cavi ty gres:;i.~res. p91Wi thinatc~n, T.R.Graham, A.Coumh, L.G. S.mi, D. I; .wh i t e* , C . T . Lewi 6 . The Lmdt?!i Hospital, London, 9 . K . S *Rc~yziI V2terinary Cc,llege, Hatfield, Herts, i 1 . K .

VIIrh WORLD CONGRESS 387

418

420

IN VITRO NAUIATICN (-1) (LVAD)

A measure of myocardial perfonmnce is given by the "Starling" m e , relating end diastolic pressure to cardiac output. we have constructed simllar curves for both the electric and pneumatic TCI LVADs relating the inlet cannula pressure with punp flow. These curves were generated using a modified -1 m c k circulatory loop consisting of a reservoir, LVAD, systemic compliance and arterial resistance. The LVADs were studied at various rates and degrees of arterial resistance. A consistent finding was the development of sub-atmospheric pressures in the inlet cannula at p w flow rates less than 4 litres during all d e s of operation.

OF THE !CHER43 CARDICSYSEMS IMPIJUWBLE FUSHER PLATE LV ASSIST DEVICES

nw I/&

The illustration shaJs typical curves from both the pnuemtic and electrical devices.

nn mssw -*g

We have observed similar sub-atmospheric pressures in both the LV and device inlet cannula follming irrplantation of these devices in calves. The physiological consequences of abnormal pressures must be considered during long term use of such devices. ? S Withinqton, M T Marrinan, T R Graham, C Sherman, C T Lewis. The London Hospital, London, UK & Thenmcardio System Inc, Woburn, Mass., USA.

CLINICAL STUDIES ON FIXATION OF FRACTURED RIBS WITH ALUMINA CERAMIC PINS AND POLYLACTIDE PINS

We have clinical.ly utilized polycrystalline alumina ceramic pins (Kyocera Co., Ltd.) for fixation of transected and fractured ribs in patients with thoracotomy o r chest injury. For the last two years, 69 pins have been implanted into 54 patients, the majority of whom had lung cancer which was resected by means of extensive thoracotomy. We inserted. the pins into the medullary cavity of the ribs and added ligatures for firm fixation. Seven of these pins (10%) were displaced and two were broken. Fixation of the ribs with the pins resulted jn satisfactory chest wall movement and was effective for preventing flail chest in injury to the chest wall. Ossificasion of the transected and fractured ribs was delayed and formation of a clear zone around. the ceramic pins was observed because of their excessive rigidity during dynamic respiratory motion. We are currently investigating the fixation of transected and fractured ribs with bioabsorbable polylacatide pins both experimentally and clinically. The polylactide pins have sufficient elasticity, bending strength and. biocompatibility with bone tissue. These polylactide pins were implanted into eight patients, most of whom had undergone resection of lung tumor involving extensive thoracotomy. Up to the time of writing, no pins have been d-isplaced or broken. Satoshi Watanabe, T. Valcamura, K. Chihara, 13. Wada, Y. Shimiau, S . Hitomi, S.-H. Hyon and Y. Ikada Research Center for Medical Polymers and Riomaterials, and Chest Disease Research Institute, Kyoto University, Kyoto, Japan

Artificial Organs, VoI. 13, No. 4, 1989

ABSTRACTS OF THE VIfth WORLD CONGRESS

421 FLOW PATTERNS IN A VACUUM FORMED PHILADELPHIA STYLE VENTRICLE

As part of the continuing effort to obtain an Investigational Device Exemption from the FDA, the intraventricular fluid flow patterns i n a PHILADELPHIA HEARTTM were studied. Neutrally buoyant resin beads suspended in solution and illuminated were pumped by the ventricle while high speed movies (100 feet per second) were taken to obtain streamlines from the bead motion. A St. Jude bileaflet valve was first positioned in the inflow orifice with i ts leaflet axis parallel to the inlet-outlet plane. It was then reoriented so that its axis was perpendicular to the same plane. Streamlines were also obtained with a polyurethane trileaflet valve in the inflow position.

Analysis of the movies indicates that with the St. Jude valve in first orientation, the fluid flows clockwise in a smooth circular pattern with good wash out and little turbulance. With this mechanical valve in the perpendicular orientation there is considerably more turbulance but the overall pattern remains similar. The flow with the polyurethane trileaflet valve breaks up and does not follow the same circular course. It also appears that there may be areas of relative stasis between the valve and the ventricular wall. These two phenomenon are the result of this valve's centralized orifice. The results from this study are consistent with the device retrieval data from the in ViVQ animal implants. D, Wurzel*, K.B. Chandrant, R. Schoephoerstert, J. SDrinebornt. G. Hansen*. L.S. Yu". W.J. Kolff" *Ca;diac Systems, Inc. Con.shohocken, PA. USA tuniversity of Iowa Iowa City, Iowa USA "University of Utah Salt Lake City, Utah USA

423 P ~ ~ o P I I E N A z , F u N o T I c N ~ T H E ~ OF LVAD REcIPImWs.

Recently, many cases with LVAD can recover acute heart failure, but few can survive w i t h keeping functions of various other organs. We recognize renal function as one of important functi.ons for survival and studied it on 10 LVAD cases who were alive over 5 days after rmval. Fhaluation was made by profiles of plasma creatinine(Cr) and blood urea nitrogen(BUN) levels. In 3 cases, who received W A D after prolonged ischemia and needed dialysis therapy earlier in spite of pumping, Cr continued to increase during pumping. In other 7 cases Cr levels were 1.OiO.3 rrg/dl before application, 1.7&0.5mg/dl on the 1st pumping day, 1.8&0.6mg/dl on the day just before weaning process, 1.9&0.7q/dl on the mid-day of weaning process, 2.Ot0.7mg/dl on the last pumping day, and 2.7i0.8mg/dl after removal. Changes in Cr dur ing pumping were not significant, but there were significant increases between before and after remsval. BUN also showed signific;i:lt il crease in this time. Betwen these stages right atrial pressure increased significantly and in mny cases mean arterial pressure or total flow went down and administered doses of catechol- mines had to be increased. These factors might have s m influences on this deterioration of renal function. In conclusion, renal function in LVAD cases mrsened before application and after removal of LVAD. We had better endeavor to indicate LVAD with earlier decision and remove it after sufficient recovery of cardiac function. A.Yagura, H.Takano, Y.Taenaka, H.Ncda, E.Tatsumi, M.Kinoshita, HSekii, E.Sasaki, Y.Kito, K.Tanaka, K . K w n , T.Hirata, T.Fujita, T.Akutsu and H.Manabe. National Cardiovascular Center, Osaka, Japan

422 EIGHTEEN YEARS' EXPERIENCE WITH THE BJ~RK-SHILEY TILTING DISC PROSTHESIS

Between 1 9 7 0 and 1988, 382 Bjgrk- Shiley valve prosthesis have been implanted in 3 0 1 patients in Mie University Hospital. 7 4 had aortic, 1 6 8 mitral, 3 tricuspid, 3 pulmonic, and 5 9 multiple valve replacement. Operative mortality ( 3 0 days) was 5 . 4 % for aortic valve replacement(AVR),2.9% for mitral valve replacement(MVR),11.9% for multiple valve replacement. The overall late mortality was 9 . 8 % , but cardiac related in late mortality was 5 . 6 % . There are 9 9 . 3 % follow up from 4 months 1 9 years (mean 5 . 5 years) and a total follow up of 1 5 8 5 . 5 patient years. The actuarial survival curve showed 63.4% for AVR and 80.4% for MVR at 1 8 years, and 8 3 . 3 % for multiple valve replacement at 1 3 years. Thromboembolic complication occurred at incidence of 0.88%/p-y on aortic,0.77%/p- y on mitral and 0.88%/p-y on multiple position. The incidence of reoperation was 1 .07%/p-y. There were no cases of mechanical failure.

In conclusion, this experience indicates that BjBrk-Shiley valve is safe and durable cardiac prosthetic valve.

Isao Yada, Yuo Kanamori, Kazuhiro Tani, Takatsugu Shimono, Kuniyoshi Tanaka, Tdnotsu Morimoto, Tetsuo Mizutani, Minoru Kusagawa Depart. of Thoracic Surgery Mie Univ. School of Medicine

424 PEUDRHAIICE CHARACTEXISTICS OF LINEAR PULSE MOTOR DRIVEN ARTIFICIAL HEART

LINEAR PULSE MOTOR A l i n e a r p u l s e m o t o r (LPM-S88) h a s b e e n d e s i g n e d a n d d e v e l o p e d by o u r groop. The LPM w e d e v e l o p e d (LPM-S88) i s small i n s i z e , 80 mi l l i - l i t t e rs i n v o l u m e , 600 g r a m s i n w e i g h t , a n d is p o s s i b l e t o g e n e r a t e a s t a t i c t h r u s t o f 94 Newtons wi th a n i n p u t power o f 4 Watts. T h e s t a t i c t h r u s t / v o l u m e r a t i o is 23.5 N / W , w h i c h is a b o u t 1.5-10 times b i g g e r t h a n t h a t o f LPMs u s e d b e f o r e . T h e t h r u s t / v o l u m e r a t i o a n d t h e t h r u s t / m a s s r a t i o are 1.07 N/mL a n d 0.16 N/g , r e s p e c t i v e l y . E a c h c h a r a c t e r i s t i c v a l u e o f t h i s LPM is i m p r o v e d b y a f a c t o r o f t w o t o t e n t h a n t h a t of a n y compar- a b l e d e v i c e u s e d t h u s f a r , m e a n i n g t h a t t h e b e s t v a l u e s i n t h e w o r l d h a v e b e e n a t t a i n e d .

T h e LPM was d r i v e n by f u l l - s t e p a n d m i c r o - s t e p d r i v e s of t w o - e x c i t a t i o n , r e s p e c t i v e l y . I n t h e case of t h e m i c r o - s t e p d r i v e , LPM h a s a b e t t e r p e r f o r m a n c e t h a n t h a t o f t h e f u l l - s t e p d r i v e f r o m t h e v i e w p o i n t o f n o i s e , t h r u s t a n d t e m p e r a t u r e rise. M a n u f a c t u r e d a r t i f i c i a l h e a r t c o n s i s t s of t h e LPM a n d a b l o o d pump w i t h a p u s h e r c u p . I n t h e mock test of t h e a r t i f i c i a l h e a r t d r i v e n by m i c r o - s t e p , t h e h e a r t was c a p a b l e o f g e n e r a t i n g c a d i a c o u t p u t o f 5 .5 l i t t e r s / m i n w i t h AoP maximum /minimum o f 115/70 mmHg u n d e r p r e l o a d o f 11 mmHg. I t i s e x p e c t e d t h a t t h e L P M - a r t i f i c i a l h e a r t c o u l d b e a p p l i c a b l e t o t h e a n i m a l i n t h e n e a r f u t u r e . However , i t i s a l s o d i s c u s s e d t h a t t h e p r o b l e m t o b e s o l v e d i s t h e d u r a t i o n of t h e s u p p o r t i n g mecha- n i s m o f t h i s LPM.

MOCK TEST

H.Yamada' .K.Kawakatsu ' . S . N i s h i w a k 1 ' .M.Karita' . Y .Mi tamura3 & T . A k u t s u '

3 H o k k a i d o U n i v . , & ' N a t i o n a l Cardio V a s c u l a r C e n t e r S h i n s h u U n i v . , ' S h i n k o E l e c t r i c C o . ,



425 PRESERVATION OF ISOLATED-PERFUSED RAT HEART WITH STABILIZED HEMOGLOBIN SOLUTION

E f f e c t s o f newly i n t r o d u c e d m o d i f i e d hemoglobin ( s t a b i l i z e d hemog1obin:SHb) on t h e i s o v o l u m i c p r e s s u r e development(LVP), co rona ry f l o w and ECGs were examined i n i s o l a t e d , p e r f u s e d r a t h e a r t s .

The h e a r t w a s p e r f u s e d w i t h SHb-so lu t ion c o n t a i n i n g 6 g / d l a t a c o n s t a n t s t a t i c p r e s s u r e o r a t a c o n s t a n t f l o w r a t e . T h e r e was n o deve lopmen t o f a r r h y t h m i a s d u r i n g p e r f u s i o n w i t h SHb s o l u t i o n . I n t h e h e a r t s p e r f u s e d a t a c o n s t a n t p r e s s u r e , t h e c o r o n a r y f l o w d e c r e a s e d t o a b o u t 5OZ of t h e c o n t r o l h e a r t p e r f u s e d w i t h Krebs s o l u t i o n . The LVP and c a r d i a c f u n c t i o n a s s e s s e d by p r e s s u r e - volume r e l a t i o n i n SHb-perfused h e a r t s were b e t t e r m a i n t a i n e d f o r 60 min t h a n t h o s e i n s t roma- f r e e hemoglobin(SFH) s o l u t i o n p e r f u s e d h e a r t s . hken p e r f u s e d a t a c o n s t a n t f l o w ra te , t h e c o r o n a r y p e r f u s i o n p r e s s u r e i n c r e a s e d i n SHb- p e r f u s e d h e a r t s , b u t t h e c a r d i a c f u n c t i o n w a s w e l l i x a i n t a i n e d . R e s u l t s were compared w i t h SFH, o r h y d r o x y e t h y l s t a r c h ( H E S ) s o l u t i o n p e r f u s e d h e a r t s . P r e s e n t e x p e r i m e n t s showed t h a t SHb s o l u t i o n c o u l d p r e s e r v e f u n c t i o n o f i s o l a t e d p e r f u s e d ra t h e a r t s b e t t e r t h a n SFH and HES s o l u t i o n s and t h u s , s u g g e s t t h a t SHb s o l u t i o n c o u l d be s u i t a b l e f o r a oxygen-ca r ry ing p e r f u s a t e f o r p r e s e r v a t i o n of v a r i o u s o r g a n s f o r o r g a n t r a n s p l a n t a i o n .

l ’akashi Yamakaws, S h y u i c h i I w a s a k i , K a t s u h i d e Ni s h i . Department o f pharmacology, Kumamoto U n i v e r s i t y F led ica l S c h o o l , Kumamoto, J apan

427 SEPARATION OF T AND B LYMPHOCYTES BY NEW 3I)SORBENTS W I T H POLYSACCHARIDES

Lymphocytes occupy a n i m p o r t a n t p o s i t i o n .ti1 t h e immune sys t em. A s T and B lymphocy tes are t h e s u b p o p u l a t i o n s of lymphocytes and have s i g n i f i c a n t f u n c t i o n s i n c e l l u l a r immunity <is w e l l a s i n humoral immunity r e s p e c t i v e l y , .it seems t h a t d e v e l o p i n g t h e t e c h n i q u e t o s e p a r a t e T and B lymphocy tes w i l l be u s e f u l for d i a g n o s i s and t h e r a p y o f immunological d i s e a s e s a s w e l l as f o r u n d e r s t a n d i n g t h e immune c e a c t 3 ons.

W e have i n v e s t i g a t e d t h e s e p a r a t i o n , or y r l f i c a t i o n t e c h n i q u e , of T and B lymphocy tes !using t h e m a t r i c e s ( a c r y l i c b e a d s , c h i t o s a n b e a d s ) i m m o b i l i z i n g c a r b o h y d r a t e s c o v a l e n t l y , 13rxause t h e m o l e c u l a r s t r u c t u r e s of ‘ & r b o h y d r a t e s a r e e x p e c t e d to p l a y a n i m p o r t a n t role i n c e l l u l a r r e c o g n i t i o n s of v a r i o u s n a t u r a l m a t r i c e s .

A s t h e r e s u l t , it w a s found t h a t p e c t i n a s a l i g a n d had s p e c i f i c a f f i n i t y t o B ly!i!phocytes, g r a n u l o c y t e s and monocytes i n human p e r i p h e r a l blood ( y i e l d o f T cells: over 70%. c o n t a m i n a t i o n w i t h B c e l l s : a b o u t l%), on t h e o t h e r hand, gum a r a b i c a s a l i g a n d had s p e c i f i c a f f i n i t y t o B lymphocytes i n mouse s ? l e e n ce l l s ( y i e l d o f T cel ls : 30%. c o n t a m i n a t i o n w i t h B c e l l s : a b o u t 1%).

I t seemed t h a t t h e s p e c i f i c i t y w a s b a s e d sn t h e f l e x i b i l i t y and t h e d e n s i t y o f a n i o n i c q roups of p o l y s a c c h a r i d e s c h a i n s .

!!uichi ~ Y a m a m o t o , Masako Nagoya, H i ro fumi Yura, “‘l’oshihiro Akaike ?ERUMO Corp., Sh izuoka , J a p a n , *Tokyo U n i v e r s i t y o f A g r i c u l t u r e & Technology, Tokyo, J a p a n

426 A NEW HCPATOCYTE PREPARATION FOR METABOLIC ASSIST DEVICE ON ARTIFICIAL LIVER SUPPORT.

L i p o p h i l i r h o l l o w - f i b e r membrane t e c h n i q u e uL i l i z i n g i s o l a t e d h e p a t o c y t e s h a s been s t u d i e d i n t h e deve lopmen t c f a r t i f i c i a l l i v e r s u p p o r t . H<iwever i s o l a t e d h e p a t o c v t e s w e r e n o t s t a b l e f o r I o n ? term c i r c u l a t i o n on e x t r a c o r p o r e a l s y s t e m . I n t h i s e x p e r i m e n t , hcpaLocy tes were i so l ; a t ed f rom a r a t a f t e r p o r t a c a v a l s h u n t , dlid ‘b’ei-e et!i:apsulated w i t h C n - a l g i n a t e and were examined

% , t i e t h e r t l , i s iii!nrovement and s t a b i l i z a L i o n of t h e i r imetabol L, i u n \ . i ion W ~ I - ~ . . i< . l i ievrd.

Nail Wistar r a t s wc;,hiii:: :!J[1-250?, vcrc’ I I . . ,~

in t h i s e x p e r i m e n t . H e p a t o c y t e s were i s o l a t e d by enzyme d i g e s t i v e method j u s t on 1 week a f t e r p o r t a c a v a l s h u n t , and t h e i r s u s p e n s i o n (1x10 c e l l s / m l ) w e r e e n c a p s u l a t e d by 1% C a - a l g i n a t e gel . 1 ml! of p h e n o l s o l u t i o n w a s c i r c u l a t e d i n i n s i d e o f l i p o p h i l i z e d p o l y e t h y l e n e membrane, and t h e c u l t u r e medium suspended w i t h e n c a p s u l a t e d hepa to - c y t e s was a l s o c i r c u l a t e d i n o u t s i d e o f t h e membrane. Pheno l and i t s g l u c u r o n i d e were measured by IIPLC.

The Permeated p h e n o l t h r o u g h l i p o p h i l i z e d p o l y e t h y l e n e membrane w a s g l u c u r o n i d a t e d by e n c a p s u l a t e d h e p a t o c y t e s . The e f f i c i e n c y of g l u c u r o n i d a t i o n on t h e h e p a t o c y t e s i s o l a t e d from a rat w i t h p o r t a c a v a l s h u n t was much h i g h e r t h a n t h a t from a normal ra t .

I n c o n c l u s i o n , h i g h s t a b i l i t y and h i g h e E f i c i e n c y were a c h i e v e d by t h e m o d i f i c a t i o n of h e p a t o c y t e s and t h i s m o d i f i c a t i o n w a s t hough t o b e b e n e f i c i a l f o r a r t i f i c i a l l i v e r s u p p o r t .

T e t s u Yamamoto, S h i n i c h i K a s a i , A k i t o s h i Kak i saka , N a r i h i r o Ohe, H i c h i o Mito 2nd Dept. o f S u r g e r y , Asahikawa Med ica l C o l l e g e , Asahikawa, J apan

428 MEMBRANE DESIGN FOR EXTENDING THE LONG-LIFE OF IMPLANTABLE GLUCOSE SENSOR

The ma jo r o b s t a c l e f o r deve lopmen t of long- l i v e d g l u c o s e s e n s o r i s t h e d e c l i n e o f b i o a c t i v i t y o f i m p l a n t e d s e n s o r . To p r e s e r v e i n v i v o a c t i v i t y , w e c o a t e d s e v e r a l a n t i c o a g u l a b l e m e m b r a n e s ; p o l y v i n y l a l c o h o l ( P V A ) , a l g i n a t e - polylysine-alginate(APA), anthron(ANT; s l o w l y h e p a r i n releaser 1 , and p o l y e t h y l e n e ox ide (PE0) membranes, on the g l u c o s e s e n s o r . We i m p l a n t e d t h e s e s e n s o r s i n s u b c u t a n e o u s t i s s u e of normal d o g s and c o n t i n u o u s l y mon i to red t i s s u e g l u c o s e l e v e l s . D u r i n g i m p l a n t a t i o n , i v g l u c o s e was s e q u e n t i a l l y l o a d e d and i n v i v o c a l i b r a t i o n of t h e s e b i o a c t i v i t i e s were c a r r i e d o u t .

The o u t p u t s o f PVA, ANT, a n d PEO s e n s o r s d e c r e a s e d g r a d u a l l y a f t e r i m p l a n t a t i o n and l o s t t h e i r b i o a c t i v i t y a t t h e 8 t h day . However, t h e i n v i v o a c t i v i t y ( mean+SD) of APA s e n s o r i n c r e a s e d u n t i l t h e 3 rd day (124229%) and t h e n g r a d u a l l y d e c r e a s e d t o 70510% of t h e i n i t i a l l e v e l a t t h e 1 5 t h day. I n v i v o r e s p o n s e times o f t h e s e n s o r w e r e l e s s t h a n 1 0 2 2 m i n a g a i n s t g l y c e m i c f l u c t u a t i o n . H i s t o l o g i c a l e x a m i n a t i o n s showed t h e n e g l i g i b l e i n f i l t r a t i o n and t i s s u e r e a c t i o n i n t h e i m p l a n t e d si tes.

T h e s e d a t a i n d i c a t e d t h a t 1) a t l e a s t a s l o n g a s 1 4 d a y s , t h e i m p l a n t e d g l u c o s e s e n s o r mon i to red e x c u r s i o n s of t h e plasma g l u c o s e and 2 ) f u r t h e r i m p r o v e m e n t o f membrane d e s i g n m i g h t e x t e n d t h e d u r a t i o n o f t h e c o n t i n u o u s g lycemic m o n i t o r i n g bv t h e s e n s o r . -~ Y . Y a m a s a k i , R .Kawamor i , N . U e d a , M . S h i c h i r i * , T.Kamada. F i r s t Dept . o f Med., Osaka Univ. Med. S c h o o l , ” D e p t . o f M e t a b o l i c Med . , Kumamoto U n i v . Med. Schoo l .

Artificial Organs, Voi. 13, No . 4, 1989


429 A SAFE AND REASONABLE ANTICOAGULATION FOR HEPATIC SUPPORT SYSTEM USING FUT-l75(FUT) AS AN ANTICOAGULANT

FUT anticoagulation and an additional effect of dipyridamole for hepatic support system have b e e n i n v e s t i g a t e d i n t h e v i e w o f biocompatibility and pharmacodynamics.

Donor plasmapheresis was performed in dogs using membrane plasma separater and 300 m l of filtrated plasma was obtained within 30 minutes. These dogs were divided in to two groups, 50 mg/h of FUT alone was infused(gr0up A, n=10), and same dose of FUT and 25 mg/h of dipyridamole were infused(group B, n=5) during plasmapheresis Moreover, BR601 or Ionex(adsorbent for bilirubin and bile acids) plasma perfusion under the same anticoagulation was succesfully carried out. In clinical studies on the hepatic support therapy using FUT(50 m g / h ) was performed 8 pat i ent s .

In dog experiments, RBC counts and Hemacrito- crit value were almost stable, but WBC counts decreased to about 70 % of the previous value. Platelets counts were about 60 % and 80 % of the previous values, in group A and B, respectively. In clinical studies, all patients had no remarked side effects, especially bleeding troubles which were sometimes experienced when heparin was used as an anticoagulant.

FUT was pharmcodynamically proved to be a safe and reasonable anticoagulant for hepatic support in our experimentaland clinical studies, and is now routinely used for hepatic support.

2. Yamazaki, M. Hiraishi, F. Kanai, K. Ohnishi, T. Takahama, Y. Idezuki and N. Inoue University of Tokyo, Tokyo, Japan

431 E F F E C T S OF INDWELLING OF FEMORAL C A T H E T E R S ON

!hen various kind o f catheters are indwelled in vessels,platelets o f t e n decrease, p r o b a b l y f o r its activation. In t h i s report,the effects o f catheter indwell-

ing f o r blood access on platelets and s o m e c l o t t i n g f a c t o r s w e r e examined. Two kind of catheters,i.e femoral catheters with i m m o b i l i z e d urokinase(UKFC) and dual-lumen p o l y u r e t h a n e catheters(8uinton.s catheter),were used. U K F C w e r e indwelled in 8 p a t i e n t s for 5 t o 18

days(group A) and Quint0n.s catheters w e r e in 6 p a t i e n t s for 10 to 18 days(group B). P e r i p h e r a l blood c e l l s w e r e counted and plasma c o n c e n - t r a t i o n s of FVffl:C, vWF:Ag, RCoF, plasminogen, fibrinogen, FPA and FPB were measured before a n d during indwelling a n d after pulling out t h e catheters. S i g n i f i c a n t decrease o f P l a t e l e t s w e r e o b s e r v e d

a f t e r indwelling Quint0n.s c a t h e t e r s hut n o t a f t e r UKFC. T h e increase of platelets w e r e found after pulljng out both o f t h e catheters. T h e r e w e r e no significant d i f f e r e n c e s b e t w e e n

t w o g r o u p s ahout clotting factors w h i c h w e had suontified. From these ohservasions. it w a s concluded t h a t t h e U K F C caused l e s s p l a t e l e t s d e c r e a s e t h a n the Quint0n.s catheter d u r i n g t h e i r indwelling, probably because o f its l e s s p l a t e l e t activation.

P L A T E L E T S A N D C L O T T I N G FACTORS

I a r u h i r o Yasumota, Yasunori Kitamoto. Takashi Deguchi,Yahito Nakayama,Tatsuo S a t 0 T h e 3 r d D e p a r t m e n t of internal medicine,Kumamoto U n i v e r s i t p M e d i c a l School.Kumaeoto.Japan

430 EFFECT OF LEFT VENTRICULAR ASSISTANCE IN THE VARIOUS PUMPING MODE ON SYMPATHETIC TONE

To determine the effect of the Left Ventricular Assist Device (LVAD) in various pumping mode on the sympathetic tone, Renal Sympathetic Nerve Activity (RSNA) was detected under the condition of the LVAD various mode pumping in animal experiments. A pneumatically driven sac type Ventricular Assist Device was used in this experiment. Bipolar electrodes were attached to the left renal sympathetic nerves to detect RSNA in 7 adult mongrel dogs. After detection of the RSNA, this Neurogram was amplified, and integrated by use of R-C integrator circuit. The area of the integrated nerve discharges per unit time were calculated in the computer system and were expressed as a RSNA per unit time. RSNA under the condition of the LVAD counterpulsation (CP) mode and co-pulsation (COP) mode pumping were compared with RSNA under the condition of the LVAD off.

In the both of CP and COP mode pumping, RSNA decreased in parallel to the increase in aortic pressure and pulmonary artery flow, and decrease in left atrial pressure compared with LVAD off. Compared with COP mode LVAD pumping, CP mode LVAD pumping had a mare evident effect to suppress RSNA. These data suggest that renal sympathetic tone under the condition of the LVAD pumping could be controlled by the LVAD pumping mode. Tomoyuki Yambe, S.Nitta, Y.Katahira, T.Sonobe, M. Tanaka , M. Miura*, H. Mohri *, M. Yoshizawa* & H. Takeda** Research Institute for Chest Diseases & Cancer, "Dept. of Thorac.Surg.:*Faculty of Eng., Tohoku University, Sendai, Japan

svm-u, \.oKm IWP -- I . I E S I ~ 1 i~ UT. r w \ . ~ ~ ' l b l ? l S T l ~ . h , .L<~J '1ESi HESlLTS

Th IS r.orl.: embodies the desi.%ii i>f a IIPX:

p i l e tuna t ical l:--dri\.en ventricular assist pump. From concept i uii to realisation, desien emphasis I ,au beel! o i i promot 1 1 g efficient, blood f l o ~ Ipattems ill order t o lover thromhoqeiiicitp. 'l'he j ~ i m i i , hwsirig j, of' traisprent e p h g , coated irisid? i;it h iiiicompatible polyurethane, and f'ittd 1. i th St . \'irlwiit's ~~echanical \ral\es. 'lhi housing is essentially <conical i n shape, with the outlet t . i t u a ! d at t!i? apes. The s i s of the inlet \,ondui t intersects the equatorial plane of the pump at a 45'' angle. The intent behind this unique shap- was t m achie\-e flow patterns that de\-elop smoothly f r o m diastole tu systole with iwisequent ial el imiriat ion of recirculation, tirrbularice and stasis. During diastole the flow is tangent i s 1 to the equator, forming a continuous \.-ui-tes cent~ed along the pump a x i s . IXtring systole t.he b J o d mows upcard, the vortes converging to pass i.hi-ough the lor<-resistance outlet. In bitro tests idescrited in separate presentations ) ,:orifinned the eqxcted streamlines. Outputs of up i . r -8 4.3 l / m i i L ha;-e beeii obtained wider ptiys- iological pre-load and afterload, using 1/2" c a u i u l a e . Thi-ee in vivo acute experiments with sheep have been conducted dur ing r;hich no thrombus formed idithiri t h e pump and pump function pro\.ed ivnsistent icith in vitro performance.

Chum-Siu l-e, Pl i t suo h e m , Allen H. hgent, Victor P. m a g : Cardiac Prostheses Research Laboratory, Si. \'incent's Hospital, Sydney, AUSTRALIA.



433 TAH WITHOUT VALVES 434 THE EFFECT OF' NEUTROPHIL DEPLETION ON REPERFUSlON INJURY UTILIZlNGTHE LEUCOCYTE RWOVAL FILTER

Oxygen free radicals and t h e i r metabolites generated from activated neutrophils have been implicated i n mediating the postischemic mrocardial dysfunction. In order to evaluate the effects of neutrophil depletion on reperfusion i n j u r y utilizing t h e leucocyte removal filter.we have examined several clinical cardiovascular variables i n three patients with acute myocardial infarction underwent successful thrombolytic therapy wi th the device and to compair those i n the patients without t h e device.

revealed that W showed total occlusion in its proximal segment without collaterals in a l l patients.

Thrombolvsis was performed w i t h the administration of urokinase (10,000 IU/ml. 1,000,000 I U i n tota1)mixed w i t h f i l t ra ted autologous blood.

The device was conposed of non-woven fabric of polyester (1.8rmd ,4.6g)and its removal rate of leucocytes was 98-100%.

Coronary angiography performed within 4 hours from the onset

An implanted model of the artificial heart having no ventricular inlet and outlet valves has been designed. This type of the TAH is smaller in size, its functional characteristics have been improved

differes from the traditional one. The natural ventricles are cut off along the atrioventricular groove. Aortal and pulmonary valves are preserved while xenovalves are implanted into the mitral and tricuspid positions. Then the ventricles of the TAH are sutured to this complex.

The tests in animals have showed pressure curves and blood flow in the atrium, aorta and pulmonary arteries to be close to natural.

Surgical technique of its implantation

Yegorov T.L., Dzemeshkevich S.L., Konstantinov B.A. National Research Centre of Surgery, IUoscow, USSR

435 FOSITIVE AND NEGATIVE EFFECT OF PLASMA EXCHANGE

P l a s m a exchange (PE) h a s been used t o t r e a t e c u t e h e p a t i c f a i l u r e , immune complex d i s e a s e s and i n t r a n s p l a n t a t i o n .

I n p a t i e n t s wi th a c u t e h e p a t i c f a i l u r e , t o x i c s u b s t a n c e s t h a t have not been i d e n t i f i e d c a u s e h e p a t i c coma, and p r o t e i n s y n t h e s i s is reduced . The purpose o f PE is t o remove t o x i c s u b s t a n c e s and supply d e f e c t i v e components such as c l o t t i n g f a c t o r s . F i f t e e n p a t i e n t s wi th fu lminant h e p a t i c f a i l u r e w e r e t r e a t e d wi th PE. PE w a s e f f e c t i v e i n r e c o v e r i n g consc iousness . However wi th PE procedul-e, t h e r e is some r i s k o f i n f e c t i o n and c o m p l i c a t i o n s . We have exper ienced 3 p a t i e n t s b i t h myocardial i n f a r c t i o n , 1 wi th a n a p h y l a c t i c shock and 1 wi th c i r c u l a t o r y f a i l u r e , d u r i n g or a f t e r PE. Three of them d i e d o f c o m p l i c a t i o n s . Therefore we d o n ' t use PE once a p a t i e n t r e a c h e s t o remiss ion p e r i o d .

On t r e a t m e n t o f immune complex d i s e a s e s and t r a n s p l a n t a t i o n , we should s e l e c t t h e methods having lower r i s k t h a n PE, because it is n o t necessary t o s u p p l y d e f e c t i v e f a c t o r s . We always use c r y o f i l t r a t i o n which can remove some a n t i - b o d i e s , macromolecules and immune complexes.

Natoki Yonekawa*, Jun-ichi Meguro*, Kazutaka Kukita', Akio Kawamura*, Nobuhiko Abe**, Kazutoshi S e t o f * , Naoki Kobayashi**, T a t s u r o I r i e * * , Ken-ichi Kawamura**, Toshio Higa**, Masaharu Kasai**, Teizo Ariyama***, Keiko Makitax*** 'Cept. o f Surgery , **Dept. o f I n t e r n a l Medicine, Sapporo Hokuyu H o s p i t a l , A r t i f i c i a l Organ & Trans- p l a n t a t i o n H o s p i t a l , Sapporo, **+2nd Dept . o f S w g e r y , Asahikawa Medical Col lege , Asahikawa, X X * f l s t Dept. of Surgery , Hokkaido Univ . , Sapporo, JaDan

Clinical cardiovascular pt.with device pt.without device variables (n-3) (F5)

mean IR 0.44 0.35 mean IST 0.22 0.24 w a n IT -0.15 -0.21

segmental shortening measured by U f f i Ih. af ter r e a n a h t i o n ( % ) -38.4 -50.2

Frequency of VPB VPB/total beats(%) 3.8 10.7

~~ ~ ~~

These data suggest that the leucccyte removal f i l t e r is effective to reduce reperfusion arrhythmia i n coronary thrombolysis and activated neutrophils may play an important role i n "Stunned myocardium".

yumika Yokoyama , Yasunor i Kutsumi , Kiroshi Tada , Toshihiro Misava,.Soo so0 Kint,Tsupuhiko Nakai ,Susumu Kiyabo, lliroshi Kamata' Fukui Medical Schoo1,"Asahi Medical Inc. ,Japan

436 USE OF THE DUPONT ANTIBODY REMOVAL SYSTEM TO REMOVE CLOTTING FACTOR INHIBITORS FROM CONGENITAL AND ACQUIRED HEMOPHILIACS

c o n s i s t i n g of two P r o t e i n A-Sepharose columns and a column r e g e n e r a t i o n ins t rument t o t r e a t p a t i e n t s who have an t ibody i n h i b i t o r s t o s o l u b l e c l o t t i n g f a c t o r s . Ten of t h e s e p a t i e n t s w e r e c o n g e n i t a l Type A hemophi l iacs w i t h i n h i b i t o r s t o F a c t o r V I I I , f i v e p a t i e n t s had a c q u i r e d i n h i b i t o r s t o F a c t o r V I I I , and one p a t i e n t had an a c q u i r e d i n h i b i t o r t o von W i l l e b r a n d ' s f a c t o r ; 1 3 of t h e s e p a t i e n t s were t r e a t e d because t h e y w e r e exper ienc- i n g a c r i t i c a l b l e e d i n g e p i s o d e . A t y p i c a l t r e a t - ment c o u r s e w i t h t h i s sys tem c o n s i s t e d of a d s o r b i n g two t o t h r e e of t h e p a t i e n t ' s plasma volumes d u r i n g e a c h of t h r e e t o s i x immuno- a d s o r p t i o n procedures performed on s u c c e s s i v e days . The c o n g e n i t a l hemophi l iacs had p r e t r e a t - ment i n h i b i t o r t i t e r s r a n g i n g from 13,100 t o 8 Bethesda I n h i b i t o r U n i t s (BIU) and averaged a 75% r e d u c t i o n i n i n h i b i t o r t i t e r a f t e r t r e a t m e n t . The a c q u i r e d F a c t o r V I I I i n h i b i t o r p a t i e n t s had i n i - t i a l i n h i b i t o r t i ters r a n g i n g from 1,587 t o 4 B I U and averaged a 91% r e d u c t i o n i n i n h i b i t o r t i t e r a f t e r t r e a t m e n t . The a c q u i r e d von W i l l e b r a n d ' s p a t i e n t s topped b l e e d i n g a f t e r two immunoadsorp- t i o n procedures and t r e a t m e n t w i t h Humate P . Eleven of t h e o t h e r 12 p a t i e n t s t h a t were b leed- i n g achieved hemostas i s a f t e r t r e a t m e n t w i t h t h i s sys tem and o t h e r a p p r o p r i a t e medica t ions such a s F a c t o r V I I I o r immunosuppressive d r u g s .

We have used a n an t ibody removal system

J e r r y R . Yordy', Robert M. Watt1, and t h e Hemophilia C l i n i c a l T r i a l Group, l C e n t r a 1 Research and Development Department, E . I . DuPont d e Nemours & Company, Glenolden, PA 19036, USA.


392

437

439


CHARACTERISTICS OF NEO RED CELLS AND THEIR IN Vrvo OXYGEN TRANSPORT CAPACITY

The newly developed artificial red blood cells named Neo Red Cells (NRC) have been tested on their characteristics. NRC are oligolameller vesicles ccmposed of hydrogenated soy phosphatid- ylcholine, cholesterol and myristic acid = 71712, in which 45wt% hemoglobin ( H b ) is encapsulated. NRC'S mean diameter is 0 . 2 ~ r n and Hb encapsulation efficiency is 1.3 - 2.2 (Hb gllipid 9). By co-encapsulating allosteric effector inositol hexaphosphate (IHP) with Hb, oxygen transport efficiency of NRC was able to be controlled as equal as or m r e than that of the erythrocytes. Aggregation of NRC in plasma was prevented by surface modification with polyethylene glycol covalently bonded phospolipids.

85% blood exchange transfusion experiments were conducted with rabbits to examine NRC's in vivo oxygen transport capacity and safety. Rabbits infused with saline or NRC not containing IHP died within a few hours or in 16 to 18 hours due to insufficient oxygen delivery to the tissues. Rabbits infused with NRC containing IHP, however, survived over 24 hrs, their blood lactate level, pH and body temperature returning to normal. Histopathological examination showed disseminated intravascular coagulation (DIC) occurring on rabbits infused with NRC tend to aggregate in plasma, while rabbits infused with NRC prevented fran aggregation in plasma showed no DIC. Except for the phagocytosis by RES, toxicity observed with livers, kidneys, lungs and pancreases was negligible. Hiroshi Yoshioka, Kazuhiko Suzuki, Yuuii Mivauchi, Akira M s h i Technicdl R&D Division, Terumo Co., Fuji, Shizuoka, Japan

OPTIMIZATION OF THE DRIVING CONDITION OF THE VENTRICULAR ASSIST DEVICE

This study presents a new method of keeping an optimal driving condition for regulating the outflow volume from the ventricular assist device (VAD).

pneumatic drive unit of VAD are positive drive pressure Ievel(pp), negative drive pressure level(p,) and systolic duration(w). The experimental results from a mock circulatory system have revealed a law of the relationship between the stroke volume and 10. i.e., su(w) . The law is as follows: the pattern o f su (w) is specified by the combination of the positive pressure characteristic curve(PPCC) and the negative pressure characteristic curve(NPCC). PPCC depends mainly o n Pp. and NPCC depends mainly o n both PN and the heart rate(HR).

s u ( w ) enables us to avoid thronbosis or hemolysis. I t is either the point where PPCC begins to saturate or the point of intersection of PPCC and NPCC. The former happens when PN is s t r o n g enough o r HR is low enough. and t h e latter happens when PN is weak enough o r HR is high enough.

operating point is as follows:

where z denotes the time when the value of outflow rate beains t o be zero from oositive.

The adjustable control inputs t o our

The optimal operating point o n the curve of

The algorithm for keeping the optimal

i f z>w then increase w else let w=z.

- Makoto Yoshizawa', Jin-Shan Feng', Hiroshi Takeda' and Shin-ichi Nitta' *

*Faculty of Engineering, Tohoku Univ.. Sendai, Japan, **Res. Ins. of Chest Diseases a n d Cancer, Tohol iu Univ.. Sendai, Japan

438

440

INFLUENCE OF BODY TEMPERATURE ON THE NEUTROPHIL FUNCTION AND PERIPHERAL BLOOD CELL COUNTS IN EXTRACORPOREAL SYSTEM

Newly developed hemoperfusion materials must be pre-tested before clinical used, because the blood compatibility of materials were adjustable or not, especially, platelet, WBC counts, free radical and complement activity. In this study, the influence of temperature in the extracorporeal circuit on the peripheral neutrophil function (phagocytosis and production of free radicals) and counts of blood cells.

Methods: Canine were divided into two groups as preserved BT ( A ) and non-preserved BT (B). Both groups were carried out sham plasmapheresis, the contents of a system (PS-02, Toray) were blood tubes and plasma separator. The blood flow rate was 50 ml/min and plasma flow rate was 15 ml/min. The circuit of A and B group were kept on 39'C and 25.C in water bath till finished. WBC, complement, free radicals and phagocytosis of neutrophil were examined. Rectal temperature were monitored.

Results: In B group of BT had decrease about 7 . 5 ' C at 180 min but A group hadn't. Transient neutropenia was noted in both groups. There was a subsequent recovery and rebound of neutrophil after 90 min i n A group, but B group was not recovery. Comparative A(85.5 I) and B(93.5I) of CHSO, there were some different. Free radical rate of A had 2 times than those of B group due to neutorphil counts of A group also had 2 times of B group. Although, in phagocytic function, there were nearly 2 times difference between A and B group. Toyokazu Yoshioka, Thoru Tani, Koichi Matsuda, Hirohiko Aoki, Kenji Numa Department of Surgery, Shiga University of medical Science, Shiga, Japan

and Masashi Kodama

LEFT HEART BYPASS ( L H B ) OR TEldPORARY SHUNT ( T S ) ? AS A N ASSIST CIRCULATION FOR THE OPERATION OF THE GREAT ARTERY

The g o a l o f t h i s s t u d y is t o e v a l u a t e t h e d i f - f e r e n c e between LHB & TS i n e f f i c a c y on c a r d i a c f u n c t i o n when used i n a o r t i c o p e r a t i o n . Method: LHB was s e t between l e f t a t r i u m & femoral a r t e r y (FA) w i t h a c e n t r i f u g a l pump and TS was made between s u b c l a v i a n a r t e r y & FA w i t h a s h u n t t u b e i n 10 dogs i n each . The a o r t i c c ros s -c l amp w a s ap- p l i e d a c r o s s t h e t h o r a c i c d e s c e n d i n g Ao. The pa ra - m e t e r s were such : LV.Emax, LVP, LAP, c a r d i a c o u t - p u t (CO), b y p a s s f l o w , h e a r t r a t e , R e s u l t s :

AO Clamp Ao Declamp t i m e ( m i n ) P r e 5 45 90 0 60 min LV- L H B s 100% 122# 133'# 132'# / 89 Emax TSs 100% 79*# 93# 91'# / 95

L H B s 100% 101 99# 108 109 92 'O TSs 100% 87' 78*# 81* 86 90

LAP L H B s 100% 92 97 97 103 100 TSs 100% 110 115 116 116 119

'PC.05 v s p r e - l e v e l , #P<.O5 LHB v s TS I n LHBs, LVEDP & LVSWI d e c r e a s e d d u r i n g A o c lamp w i t h t h e S t a r l i n g c u r v e s h i f t i n g t o r i g h t b u t q u i c k l y coming back t o t h e pre-clamp l e v e l a f t e r declamp. I n TSs, LVEDP & LVSWI i n c r e a s e d d u r i n g Ao clamp w i t h S t a r l i n g c u r v e a l s o s h i f t i n g to r i g h t ; however , a f t e r declamp LVEDP s t a y e d h i g h w i t h t h e S t a r l i n g c u r v e s t i l l showing t h e r i g h t s h i f t i n g . I n c o n c l u s i o n , l e f t h e a r t bypass ( L H B ) u s i n g a c e n t r i f u g a l pump is a n e f f e c t i v e t o o l i n m a i n t a i n i n g c a r d i a c f u n c t i o n i n a o r t i c s u r g e r y w i t h poor c a r d i a c f u n c t i o n . Ryohei Yozu, K . Oncguchi , S . Taguch i , H . Sh imizu , H. I z e k i , H . S h i n , Y . Haga, Y . Soma, S. 'Takeuchi. K . Kawada, T. I n o u e , Dept . of S u r g e r y , Schoo l o f Med ic ine , Ke io U n i v e r s i t y Tokyo, J a p a n

Artificial Organs, Vol. 13, NO. 4, 1989


441 Son ARTIFICIAL VENTRICLES

A new s o f t a r t i f i c i a l hea r t was inplanted 'into e igh t calves. The Total A r t i f l c l a l Heart (TAH) w i t h a stroke v o l w of 65cc is made by vacuum fomlng over male m l d s . The polyurethane housfng is s o f t , f l e x i b l e and easy t o implant. Valves used were t r i c u s p semilunar polyurethane valves.

Testing i n a mock c i r c u l a t i o n aided by s l i g h t vacuum durTng d i a s t o l e showed the ventr ic les t o respond t o S t a r l i n g ' s Law. In calves excessive suction of t he d r ive systems would r e s u l t in a f a l l i n ven t r i cu la r pressure during d l a s to l e which propagated i n t o the a t r i a resul t ing i n large f luc tua t ions of pressures.

Four calves l i ved between 20 and 43 days with the implant. Broken l e a f l e t s of me valve proved to be noncatastmphic. One c a l f broke two l ea f - lets of the lnitral valve a t day 27. Speeding up the hea r t rate t o 145 beats/min wlth a sys to l e ~f 34%. a lef t d r ive pressure of 2CUkm-Jjg and a r i g h t d r i v e pressure o f 65nm Hg m p e n s a t e d the mechanical f a i l u r e o f t h e valve to t h e extent t h a t t he c a l f l ived another 16 days.

thrombosis was limited t o places where it was most l i k e l y induced by infect ion. The diaphragn housing junct ion was e n t i r e l y free o f thrombosis i n s i x of eight animals.

Although no ant icoagulants uere used,

LS Yu: J KJl'nkmann; P bbison; NBfshop; J . K o l f f ; F Yersteeg; G Burns; B Yuan; WJ Kol f f Oept. of Surgery, Univ. of I f t a h , S a l t Lake

O S P

442 CAPIOX E HOLLOW FIBER OXYGENATORS IN OPEN HEART SURGERY, CLINICAL EXPERIENCE OF CONSECUTIVE 100 CASES

In a consecutive series 100 CAPIOX E Hollow fiber oxygenators were tested in routine adult open heart surgery: CABG or valve replacement. Patient data: age: 32 - 02 (s=62) years, weight

(s=1.9) qm. bypass time 37 - 143 (s-83) minutes. 02 flow 0.5-4.3 (1,7) l/min. blood flow 3.4 - 6.5 (s-4.7) l/min, blood temperature 38.3 - 21 C, body temperature 38 .- 27 (s-31) C. Fi02 50 - 100 (s-68) % Hypothermia period: pO2 523-102 ( ~ = 2 5 8 ) m H g , pCO2: 44.5 - 20.3 (~=33,9) mmHg, 02 Flow: 2 . 5 - 0.3

59-135 kg ( ~ = 7 9 ) . BSA 1.62 - 2.55

(s-0,621 l/min, Fi02: 50 - 7 0 ( ~ ~ 6 2 ) %

Djsc_u_ssi.o.n-: The installation of the CAPIOX E oxygenator proved to be easy and quick. oxygenation and de- carboxylation capacities of the device are excellent even in very low gas flow rates and extreme BSA, as graphs demonstrate, the heat exchanger is sufficient. Complications as platelet reduction or hemolysis were not observed.

Harald E. Zeplin MD, Ralph Honigmann. Uwe Lewandowsky: Clinic for Thoracic & Cardiovasc. Surgery, Fulda Medical Center, 6400 Fulda, FRG


abstracts of the viith world congress

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