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Journal of Parenteral and Enteral

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 DOI: 10.1177/0148607192016001011

1992 16: 18SJPEN J Parenter Enteral Nutr16Th Clinical Congress Abstracts Paper Presentations

  

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18S 16TH CLINICAL CONGRESS ABSTRACTS

PAPER PRESENTATIONS

1 Nutrition SupportEFFECT OF A LIQUID DIET WITII SOLUBLE FIBER ON TRANSIT TIME IhlCOMPARISON TO FIBER-FREE AND SELF-SELECTED DIET IN ~-IEALT1IYVOLUNTEERS. R. Meier, MD, A. Rowedder, MD, 11. Schneider, PhD , A. Christ,MD, K. Gyr, MD. Der -rtment of Medicine, Kantonsspital, Liestal, lSandoz Nutrition,Bern. SwitzerlandFiber supplementati . is thought to decrease the incidence and severity of diarrhea

in patients receiving fihcr-free liquid diets. Ttre aim of the study was to compare theeffect of a 100°!n soluble fil{er-containing diet (21 g/1)(SD + F) with a soluble standardfiber-free diet (Nutrodrip )(SD) and a self-selected diet (SSD) on gut transit time.After a one-week baseline period with SSD, a randomized cross-over study was per-formed in 12 healthy volunteers (range 23-~10y) consuming isocaloric amounts of a)SD+F or b) SD each for 7 eavs with a wash-out week inbetween. Oral-coecum transittime (OCT) was assessed by lactulose H2 breath test and colonic transit time (CTr) bya radioopaque marker technique. Stool frequency (SF) and consistency were recorded.The results are in mean ± SEM.

1. The soluble fiber addition did not affict OCT. 2. Compared to SSD, Cri was in-creased with both liquid diets. 3. SD+F showed a significantly increased CrT com-pared to SSD and SD. 4. Daily SF was not different, but a trend towards increased SFwas observed with SD whercas soluble fiber reversed this effect.In conclusion, liquid diets containing soluble fiber may be beneficial for enterally fed

patients with diarrhca due to prolongation of CTT without affecting OCT.

2

EFFECT OF SOY POLYSACCHARIDE (SP) SUPPLEMENTATION OF TOTAL ENTERALNUTRITION (TEN) FORMULAS ON LARGE BOWEL SHORT CHAIN FATTY ACID (SCFA)PRODUCTION IN HUMANS. M.I. McBurney, PhD, B. Beyde, R.D. and A.B.R.Thomson, MD, PhD. Departments of Foods & Nutrition and Medicine,University of Alberta, Edmonton, AB.

SCFA derived from large bowel fermentation of dietary fiber may bebeneficial in the prevention of GIT atrophy and bacterial translocation.We have shown that large bowel energy absorption can be accuratelyestimated from in vitro fermentations of ileal effluent with human fecalmicrobiota (1991 Can Fed Proc 34:53). To determine the effect of SPsupplementation of TEN diets on SCFA production, 8 healthy ileostomatesrandomly consumed 5 isocaloric TEN diets composed of 100:0, 75:25,50:50, 25:75, 0:100 percent kcal from Ensure:Enrich (Ross) for 3 dayperiods to provide 1.9, 8.9, 16.0, 23.8, and 30.Og SP/2000 kcal,respectively. Ileal effluent was collected for 2 days. Aliquots (0.2g)of lyophilized effluent were fermented in vitro for 24h with human fecalinoculum from 3 healthy donors and SCFA production was measured. SCFAproduction (mM/d) increased significantly (P < 0.0009) with Enrichintake to provide 254.1, 355.9, 460.9, 4:,.0, and 524.8mM/d,respectively. Molar ratios of C 3, and C 4 were unaffected by Enrichintake (P < 0.1). Assuming 100i ~C~A absorption and gross energyconversion values for each SCFA, regression analyses indicated thatmaximal SCFA energy absorption from the large bowel = 63.4kcal +

3.4kcal/g SP (r=.83, P<. 0001). The results suggest that SPsignificantly increases SCFA production and that SP has an energy valuegreater than 0 kcal/g. (Supported by NSERC and Ross Laboratories).

3

USE OF TRIPLE LUMEN SUBCLAVIAN CATI IETERS FOR ADMINISTRATION OF TPNN. Clark-Christoff, RN, V. Watters, RN, W. Sparks, RN, P. Snyder, BA, J.P. Granl, MD Departmentof Surgery, Duke University Medical Center, Durham, NC.

Mullilumen catheters are increasingly being utilized as central vcnous acccss for TPN. Studies oftheir safcty have been compromised by small and mixed study populations and often subjectivedefinitions of sepsis. This study evaluated the safety of triple lumen vs single lumcn catheters in adefined high risk patient population using a rigid definition of sepsis. Patients were excluded from the

study who had prc-cxisting ncutropcnia (WBC r2000), were immunczsupprccscd (chemotherapy, illvpositive, organ tran~plants). who had holly burns >40%, and/or contaminated wound% about thc subela-vicular arca. Patients were randomiicd to receive either a single lumen (SLC) or a triplc lumcn (TLC)cathctcr. t7nc hundred sixty-one patients completing 7 or more days of therapy were entered into thcstudy between June 1989 and August 1991. Patients were considered at high risk of catheter sepsis byhaving one or more of the following conditions: greater than (yfl years of age, breakdown of skin

integrity, severily of underlying illness (all ICU patient.%), acute pancrcatitis, prcxncc of a tracheos-tf’myor recent head or neck surgery, and/or pre-existing infection (urinary or respiratory tract, wound,ctc.). Sixty-scvcn paticnts were tlndOMi7cd to receive a SLC and nincty-four to receive a TLC.

All cathctcrs were placcd and maintained by the Nutrition Support Team (NST). Dr,--~%ings werechanged weekly with a semipcrmeahle membrane drcssing and patients were seen on a daily basis.Bi<3ou cultures were obtained by the NST nurse using the Isolator method whcn patients mct prcdefinedseptic parameters, or had documented positive btocxt cultures. Periphcr&dquo;l and central blood cultureswere obtained simultincously for quantitative analysis. True central catheter sepsis was rccordcd if thewlony count from the central catheter lumcn was ~5 times that of thc pcriphcral blood. The incidenceof true catheter %crisis for SLC was 1.5’~ ( t /67J compared to 12.7^,~ for TLC (12M4) (p = .0073). Noenrrebtion with catheter sepsis was found with the number of insertion attempts for placement, numberof cathctcr days, or the patient’s age. We conclude that triple lumen cathcters should not be routinelywcd for intravenous nutrition in a high risk paticnt population, as defined in this study, due to anincreased risk for ccntral cathctcr sepsis.

4

UPTAKE OF GLUCOSE DURING CONTINUOUS ARTERIOVENOUS FIEMOFILTRATION(CAVI 1). R. Monaghan MD, J. M. Watters MD, S. Clancey RN, S. Moulton MSc, and E. Z.Rabin MD. University of Oltawa, Ottawa Civic Ilospital, Ottawa, Canada.CAVH is a widely used method of managing fluid and electrolyte balance in critically ill

patients with acute renal failure. Dianeal 1.5% PD101 peritoneal dialysis solution iscommonly used as a replacement fluid for the plasma ultra filtrate removed (effluent) andcontains glucose in high concentration (about 1.5 g/dL or 83 mmol!L). To evaluate the uptakeof glucose during CAVH employing predilution with Diancal, we studied twenty criticallyill patients by the analysis of timed collections of CAVIl effluent (2 hr collections, n=10, and12 hrs, n=10) and other observations. Results are expressed as mean sd.

Patient ages ranged from 18 to 81 years and APACI IE 11 scores from 5 to 39 (21 11). Serumcreatinine and BUN decreased during CAVI I in each patient, serum creatinine from 514 ± 156mmol/L to 246 ± 89 and BUN from 35 16 mmol/L to 15 ± 6, both p < 0.001 by paired t-test.The glucose concentration of Diancal was 1.40±0.15 g/dL and rate of infusion 1.39±0.43 L/hr.Effluent volume was 1.51 0.49 L/hr and glucose 0.47 ± 0.10 g/dl. CAVI I cffluent data wereunrelated to the length of collection. Glucose uptake (calculated as the product of the volumeand glucose concentration of the Diancal infused less that of the effluent collected during thesame period) was 11.9 ± 3.1 g/hr (range 4.3 to 17.6). Glucose uptake was strongly related to therate of Diancal infusion (r2 = 0.73, p < 0.001) and creatinine clearance (n=12, 49 ± 29 mL/min)to effluent volume (r2 = 0.95, p < 0.001). 5cmm glucose increased in each patient withinitiation of CAVH (from 7.4 ± 2.4 to 15.3 ± 4.4 mmol/L, p < 0.001). Total and urea nitrogen inthe CAVH effluent were 22 ± 7 and 18 ~ 1: 7 g/24hr, respectively.

The use of Diancal as a replacement fluid during CAVI is accompanied by the uptake oflarge amounts of glucose, approaching 300 g/day on average. This finding has importantimplications for the nutritional, metabolic, and respiratory management of critically illpatients during CAVI and should be taken into account in their nutritional support.

5

CAN MULTIPLE FREQUENCY BIOELECTRICAL IMPEDANCE ANALYSIS DISTINGUISH BODYWATER COMPARTMENTS? c.Gat7en. FRCS(E), M.Scheltinga, MD, II.Su7.uki, MD, T.Byrnc, MS,D.Wilmore, MD, L1b for Surgical Metabolism and Nutrition, Brigham & Womens’ Hospital, Boston MA

Resistance (R) and rcactilnce (Xc) values obtained from bioclcctrkal impedance analysis (BIA) at theusual frequency of 50 ki 17, are known to correlate well wuh total body water (TBW), but only weakly withextracellular water (ECW) or the ECW{fBW which are of prime importance during disease. To testthe hypothesis that currents of lower and higher frequencies are conducted preferentially via the ECW andTBW compartments respectively, and impealance measurement,; at such frequencies better reflcct waterdistribution, 33 healthy volunteers (17 males, 16 females, age 32 ±2.4 (SCh1), hcight 170 ±1.6 cm,weight 69 ±2 kg) were studied. TBW and ECW were determined by deuterium oxidc (10 g) and sodiumbromide (3~70, 50 g) dilution; intraccllular water (ICW) is the difference between TBW and ECW. Wholebody BIA was performed using a 50 kliz single frequency (RJL) and a multiple frequency (lkHz-1MHz)analyzcr (MFA). Resistance measurements at representative frequencies, corrected for height (IIt2/R), wereanalyzed for correlation with body water compartments and arc expressed as correlation cocmcients (r):

Hcight2/R correlated well with TBW at all frequencies; the best relationship, in which R is corrected forhcight and reactance, yield- a correlation coefficient of 0.97. lit2/R also correlated with LCW and ICW withno significant difference among frequencies, even when ttre strong correlation of ECW with TBW (r=0.81)was suppressed by partial correlation analysis. Various ratios of R at low versus high frequencies correlatedpoorly with ECW{fBW (r=0.67 at best) and not significantly better than the Xc/R ratio, as measured bysingle frequency BIA (r=O.62). We conclude tklt single frequency BIA, a rapid non-invasive bedsidetcchniquc, is able to predict TBW but does not differentiate well between fluid compartments. Howcvcr, wecannot confirm other reports that multiple frequency B1A can better assess either TBW or iL~ distribution ina group of normal individuals. It remains to be dacrmincd whether ~1FA can improve discriminationbetween body water compartments in conditions of abnormal water distribution associated with disease.

6

ENTERAL VS. PARENTERAL FEEDING AFTER TRAUMA: EFFECTS ON VISCERAL PROTEINS.K.A. Kudsk. MD, S.L. Wojtysiak, Pharm D., G. Minard, MD, N1. Croce, h1D, T. Fabian, MD. &R.O. Rrown, Pharm D., Depts. of Surgery & Clinical Pharmacy, Univ of TN, Mcmphis

Effects or enteral (EN) w. parenteral (f N) feeding on recovery from critical illnessrcmain controversial. Transferrin (Tf--N), prcalbumin (1,A), (-rcactive protein (CRr).fihn’neclln (FRN), alpha-I-acid glycuprolein (AAG), and alhumin (Al,tl) were measured

on days 1.4,7.10.15 in 6R trallma Patients with ahdol11lnal trauma indiees (ATI)of >15(15-7(r) were mndtrmilcd to EN (n~14) or rN (n=34) feeding for 15 days. IsocaloriclIsonitrogenous feedings were given at a rate ol’ I.S-2.(1 g/kg/<t or protein and :1(1-35 kcal/kg/d of non-protein calorics. Prngnostic itil&dquo;lammatory and nutritinllal indices (PINI)and t’Ni wcrc calculated. Groups were l11alched for age (EN 30.5 t 12.5/ PN 10.6 ;t10.0).ATI (EN 28.0 + 10.5/PN 27.8 :L 13.8) & ISS (EN 27.0 :t. 11.5/PN 26.8 + 12.6).

S, g., i fi ~ a,, t... in f t’A, CRp & TFN ,,, ,,I’d ill, [-.,N h,leSignificant imProvcmcnt in Icvcls of PA. CRP above wcrc 1, p uilli EN whilc simiInr

rcsplmses were noled in FIJN (all days elevated above day I, p <.(lsj, ALIJ (minimalchange from day 1). AAG (inerease from day 1 on all days, p <.05) and PNI (no signifi-cant change from day 1) between EN and PN. PINf increased significantly from bacli,,con days 7&10 only in thc PN group. EN produces greater incrca<cs in constitutive

proteins and greater decreases in acute pi~asc proteins following severe trauma.

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7

MLTF1HDLIC RESPONSE TO MULTIPLE INJURY: IS IT DIFFERENT WITH OR WI’IflOCfT

SEVERE I&OElig;IBD IN.JURY? S.R. Petersen MD, T.R. Harrington MD, M. JeevanandamPhD. Trauma Center, St. Joseph’s Hospital & Medical Center, Phoenix, AZ.Head injury is the single largest contributor to trauma center deaths.

Injury that does not involve the brain directly can lead to a cascade ofchanges in neuroendocrine system function. Contrasting the metabolicsequelae of major trauma with or without central nervous system injuryis essential for the success of nutritional management.We have studied a group of adult (age 45+5 yr) trauma patients (ISS =

31+3) having multiple injury witlmt head injury (MI, n=21) or multiplebody injury combined with severe head injury (ItHLi, n=21) 48-72 hrs aftertrauma in the fasting state. Kinetic rate measurements of protein (pri-med-constant infusion of 15N glycine), glucose (14C and 311 isotopic glu-coses)r fat (two-stage glycerol infusion)and energy (indirect ca1cr:i!’Etty)were made along with circulating hormones and substrate determination.

Similar plasma hormonal and substrate levels, daily urinary excretionand whole-body protein kinetics (breakdown and synthesis) were seen. Glu-cose and fat kinetics data are significantly different in the two groups.

--j ...~._..4..._...~. ,-,..-.., -.-....-- ...... - .. _ .~. _ _ _-

ttepatic glucose production and whole-body lipolysis are significantlydecreased in patients with severe head and multiple injuries. It seems

that the neural injury moderates the systemic effect of trauma.

8

AGGRESSIVE EARLY MANAGEMENT OF MALNUTRITION IN HIP FRACTURE PATIENTS.J. Gallagher, MD, J. Schermbeck, RD, MEd, CNSD, L. Dixon, RN, CNSN,M. Labbe-Bell, LIT, St. Francis-St. George Hospital, Cincinnati, 011.

The purpose of the study was to demonstrate that early detection andmanagement of the malnourished hip fracture patient would improve thetreatment outcome. Over 15 months, 97 malnourished patients (admissionAlbumin [Alb]< 3.5) were randomized into Control (C) or Treatment (T)groups. The groups were well matched for age, sex and fracture-type.The T-group had a small-bore nasogastric tube placed in surgery. Begin-ning the first postoperative (postop) night, the I-group received 11hours of supplementary, overnight, isocaloric tube feeding providing 933kcals. and 33 8fT1s. protein. Both groups received a normal diet andsnacks as desired. Tube feedings were continued until the patient ate75% of their caloric needs for 3 consecutive days. Nutritional proteinparameters, calorie counts, physical therapy (PT) performance, medical,surgical (Surg) and gastrointestinal (GI) complications were monitoredduring acute care and rehabilitation (Rehab) length of stay (LOS).

PT r»>1<

The T-group showed a more rapid and sustained rise in protein parame-ters, a decrease in Rehab LOS and a decrease in days to meet PT goals.Additionally, the T-group had less surgical and GI complications.

9 Metabolism I

PREFEED)NC WITII CLUTAMINE PRESERVES INTESTINAL CLLJ’TAM1NASE ACTIViTY INTIIG ENDOTOXIN-TREATED RAT. P.S. Dudrick MD, T.A. Austgen MD, M.K. Chcn MD, D.Aiillcr, B. Pickcns, and W.W. Souba MD. Dcpartment of Surgcry, University of Florida,Gainesville. FL

Glutamine (GLN) is the most abundant amino acid in the body and the amino acid most affectedby critical illness. We have previously demonstrated that endotoxemia causes a fall in muscle andliver GLN levels, a decrease in intestinal GLN extraction, and a fall in jejunal glutaminase(GLNasc, the major regulatory enzyme of glutamine metabolism) activity. This study examinedthe effects of prophylactic feeding with various diets on these endotoxin-induced alterations inGLN metabolism. Adult rats (n=45) were randomized to receive one of three cnteral diets. Diet 1was a whi2y protein concentrate base (WI’C, 6-9% of protein = GLN). The second diet consisted ofhydrolpcd di- and tripeptides (DTI’) which were also comprised of 6-9% glutamine. Diet three(UTf + GLN) consisted of di- and tripeptides with added free glutaminc (30% of total N = GLN).Diets were administeted via gastrostomy tube for four days prior to an endotoxin challenge <E. mliLI’S 10 mg/kg i.p.). All animals received 50 cc/day (5 feedings of 10 cc each/day). Diets wereisocaloric (65 kcal/day) and isonitrogenous (329 gm/day). The last feeding was given at 7 pm at thetime of endotoxin challenge. 12 hours later blood and tissue samples werc obtained. (Data = meanSEM, *p<0.001 vs WPC and DTP by ANOVA)

- -... -...... -...

Diet did not significantly affect blood CLN levels, gut CLN extraction, tissue CLN levels, or theincidence of positive blood cultures (2/15 in WPC, 2/13 in DTP, 0/13 in DT(+GLM. However, theglutamine-£nriched dipeptide diet increased mucosal glutaminase activity by 259. This increase inenzyme activity may increase the rate at which GLN is moaboli7.2d by the injumd gut mucosa.Clutamine...,nriched enteral diets may support the gut during sepsis.

10

EFFECT OF GLUTAMINE-SUPPLEMENTED TPN ON RECOVERY FROMSTARVATION ATROPHY OF SMALL INTESTINE. Y. Inoue, MD, .1.P. Grant, MD,P. Snyder, BA Department of Surgery, Duke Univercity Medical Center, Durham, NC.Glutamine supplementation of TPN has been shown to protect against atrophy of the

normal small intestine. No experimental studies, however, have been reported on theefT,~~ of glutamine on recovery from starvation atrophy. 1Ve induced sewem intestinalatrophy in rats by infusion of 5T dextrose for 7 days allowing only oral water (30% bodyweight loss). The rats were then refed with Ihl&dquo;(’e different regimens. Group CHOW wasrefed with standard rat chow (N=15), Group STD was refed with TPN containing IG~,glucose, 2.8% fat, and 4.25% standard amino acids (N=15), and Group GLN was refed withthe same solution but with 2.75% standard amino acids and 1.5% glutmmine (N=15). After7 days of ~rc-eding, rats were sacrificed to measure intestinal composition. Results were

eompnred to healthy rats:

(* p,0.01 vs STD; ** p,0.01 vs GLN and STD; by Student’s t-test)

Glutamine-supplemented TPN is superior to standard TPN in repleting small intestineafter starvation induced atrophy. Hat chow completely restores the intestine to normal.

11 1

T(IE VARIATION OF HEPATIC ENERGY CfIARGE AND MITOTIC ACTIVITY AS INFLUENCEDBY DIET IN REGENERATING RAT LIV(:R. Ming H. Chiu and Ronald II. Birkhahn. Ph.D.Department of Surgery. Medical College ol Ohio. Toledo. OH.

The relationship between hepauc energy chargc ( HEC ) and mitotic activity was investigated inparually hepatcctomi7.cd rats infused with ketone bodies. glucose or saline. Male Sprague-Dawley rats,n=130, body weight = 240:1:30 g, underwent 70% hepatectomy and installation of continuous iv feedingcatheters into their jugular veins. After surgery all rals were infused with saline for 6 hrs, then randomlyassigned to one of 3 groups infused with ketone bodies ( 18,Y,, monoacetoaccllnc. 7’7o glucose, 4% aminoacid). glucose ( 25% glucose, 4% amino acid ) or saline respectively. The infusion rate was isocaloric forketone bodics and gluc osc groups at 2.3 kcal/hr, isovolumctric for all 3 groups at 2 in l/hr. Thrcc rats fromeach group underwent cervical dislocation starting 2 hrs after surgery until 32 hrs post-surgery at 2 hrsintervals. Remnant liver biopsies were frozcn in situ, then stored in liquid nitrogen until analyxs. HECIIIEC = (ATP + I /2ADP) I( ATP+ADP+ AMP)] were measured enzymatically. Remnant livcr,;Iices werestained with hacmatoaylin and cosin for assessing mitotic activities. The data shown in the figures.During 24 to 32 hrs after parual hcpatectomy, high levels of hepatocyte mitotic activities and low HEClevels were ohscrvctf in regenerating livcrs from rats infused with ketone bodies or salinc whcn these wereeompared wnh those from rats on glucose infusions ( Two way ANOYA, p<0.0 ). It is concluded thatthe HEC and the mitotic activities after major liver rcsection were affected by the dietary intake and, therate of liver regeneration was invcrecly related to IlEe.

12

UVUR DYSFUNCTION AND ENERGY SOURCE: RESULTS Or A RANl~h117-rl) CLINICALl’RlAl.. C. Buchmiller. MA.RI1. R. Kleiman-Wexler. l’hmm D. K. rphgrnvc. MI1. D Booth. Ph D,and C. llensley, R Ph. Veterans Aflair< Medical Cenler. town City, IA

Controversy still cxiUC regarding thc mlc of Ihe carbohyùrate fat ratio on liver functionabnonnalitic, associated wUlWltc aJmmistraticm of 1 PN. We dcsigned a prospective clinical trialcomparing slanùartl carhohydrale-haseù l’1’N (R 5’7, allB1I10 aeith. 1>50. 7.5‘~ of calorics from lipids)with an i,ocaloric lipiù-hascd TPN (8 5% ammo aCIds. D-,O. 40% of calories from lipids) on 43patients exclusively on TPN ~ 2 weeks. Energy needs were calculated at til:I: 1 1 S. ’1 hc mcan

caloric intake for patients who ob4~incJ cartx,hydratc-haac<l’1’1’N (Cl 10) was 2210 while thc lipidhascd It’N (UP) group icliicvcd a mean of 22RO calories. 1VC mOnitored total hihruhin. direct

hiliruhin, alk;~lmc fhoshhatase. LUII, SC’~T anJ SGf1’. Initial liver function tcas (LIT) did nt varyai(mficatuly txtwccn Froups. Patients with pre-existing liver disease were nclnùed lhcrc waa no

sIgnificant difference in age or diagnosis hclween thc gmu~s. Mean Lt’Ts diffcred signifieantlybetween patienls who ohW incJ Cl 10 and 1.11’ hascd ’I 1’N. Data shown hclow arc group means <:1: tfie

standard error) aftcr 2 weeks of TI’N. Groups were compared with Student’s t testw.,..m:.,.,.,

Alkaline 1&dquo;&dquo;&dquo;l’hata<;c anll Y -I’.Int.nnyl tran~J’Cl’lidasc were not affected by tltc energy source of thc1l’N

In conclu’Ion. tluc 1’ff’~J’Cctivc trial reveals that the ucc of a balanced energy ’Ourcc TI’N snluticmfrcvcnm tile abnoffilalltics in 1,T7rs cnmmonly associated u Oa Tt’N. tody fro- prcvioustrialc in that ovcrfccJmg was avoided in hoth ~,rtitip~ and mcin LI Ts u-crc ncar titiniiif in patientswith mixed caloric sourcc TI’N.

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20S

13

TilE DIRECT EFFECT OF EICOSAPENTAENOIC ACID AND DECOSAPENTAENOIC ACID ONTIIB FRODUCTION OF PGr-~2 AND TxB2 BY KUPFFE-R CELLS. Con K. Ogle, Ph.D.; Jun-Zhcng Wu,M.D-: Josef E. Fischcr, M.D.; J. Wesley Alexander, M.D. - Shriners Burns Institute and University ofCincinnati Medical Center, Cincinnati, Ol I

Kupffer the fixed macrophages of the liver, are the most abundant population of macrophaga andarc able to produce greater amounts of iricliidonic acid products than other populations of macrophagl$. Itwm the purpose of this study to determine if in vilm incuhation of Kupffcr cells with eicosapentaenoie acid(EI’1B) or decosapcntaenoic acid (DI IA) could affect thc production of PGe2 and TX13~. It was hypOth~si7Cdthat Kupffcr cells could ineorporate and metaMli7e EP A and DI IA in thc absence of hepatocylc.s.Method&dquo; Rat Kupffcr cells were ootained by [- rfusion of Ihe liver with collagcnaxs and incubated for 24 hrcin M199 media with albumin alone, with 50 u’’ :J’1B bound to albumin or with 50 uh1 DIIA bound toalhumin. After 24 hrs thc fatty acids were mmo%cd and the cells cultured for an additional 3 hr.; in thepresence of merthiolate to prevent rcineorporalion of fatty acids or opsonized zymosan to stimulate theproduction of PGE2 and TxB2. The supernatants were then removed and assayed for PGr~~2 and TzBi byLLISA. Statistical analysis of thc results was done by ANOVA followed by Neuman Keuls.

The prcxluclion of PGC2 was significantly dccrcascd from thc albumin control for both EI’A (p<0.01) andDIIA (p<0.01) with merthiolale or opson’v.cd rymosan used as a stimulus. The production of TzBz was alsosignificantly decrci%cd from thc alhumin control for hoth EPA and DIIA with merthiolate (p<0.01) and

~igiiiric.intly dccmi-ed for EPA (p<0.05) with op<onized rym()!¡an used as the stimulus.

It can be concluded that Kupffcr ecll~ incorporate EPA and DIIA directly into their phospholipidnwmhranc~ with a resultant decrease in thc production of I’Gr’-2 and Txn2. These studies stress the

importance of EI’A and DIfA in l’i&dquo;Q in controlling the production of the immunomodulating prostaglandin-,P(;T~2 and Txn, in a short period of time.

14

EFFECT OF GLUTAMINE ON FATTY ACID AND GLUCOSE KINETICS.J.D. Silverberg, MD and J.M. Miles, MD, Endocrine ResearchUnit, Mayo Medical School, Rochester, MN.

It has been established that glutamine is a majoroxidative fuel for the gut and, as such, may have a specialrole as a gut nutrient. However, its effects on humansubstrate metabolism are poorly understood. In the presentstudy, glutamine (1.5 J.Lmolokg- omin-’, n=7) or saline (n=7)was infused intravenously for 3 h in normal subjects afteran overnight fast under conditions of a euglycemicpancreatic clamp (somatostatin + basal insulin + basal

growth hormone) to prevent changes in plasma hormoneconcentrations. Glucose and palmitate kinetics were

measured with constant infusions of [6 3H]glucose and

[9,lo-3H]palmitate, respectively. There was no change inglucose turnover in response to glutamine (24.6 t 1.3 vs27.2 ± 3.7 J.Lm01okg-lomin-&dquo; p=NS) or saline (21.6 t 1.7 vs21.3 3 ± 2.0 ~mol·kg’~·min’~, p=NS) infusion. Likewise,palmitate turnover did not change in response to glutamine(2.4 ± 0.2 vs 2.7 ± 0.3 J.Lmolokg-lomin-’, p=NS) or saline (2.2± 0.2 vs 2.5 ± 0.3 J.Lmolo kg-10 min-’, p=NS). Plasma concentra-tions of insulin (-30 pmol’ 1-’), C-peptide (-25 pmol’ 1-’) andgrowth hormone (-2 ng-ml-1) were unchanged during both

glutamine and saline infusion. We conclude that infusion ofphysiologic amounts of glutamine has no hormone-independenteffects on glucose or free fatty acid metabolism.

15

CAN TESTS OF PATIENTS WELL-BEING BE USED TO EVALUATE NUTRITIONAL EFFICACY ?AN AFFIRMATIVE ANSWER. L. Young, R.D.,M.S.,CNSD, M. Schelûnga, M.D., R. Bye,R.D,,M.S.,CNSD and D. Wilmore, M.D.,Brigham and Womens Hospital, Boston Ma.Nutritional effects have traditionally focused on outcome, such as nitrogen balance, wound healing, or

muscle strength. Little emphasis has been placed on how bicrchemical or physical improvement,, translateinto functional changes as perceived by the patient. Because Glutamine (Gin)- supplemented nutritionpromotes protein synthesis and improves nitmgcn balance, we assessed the mood of individualsparticipating in a randomized controlled blinded trial receiving Gin solutions. Patients, (n=25) undergoingmarrow transplantation, were randomized by the research pharmacist to receive either standard TPN(control) or Gln-containing TPN (40 grams). The wlutions were isocaloric and isonitrogenous and wereadministered until the patient was eating 50% of estimated requirement-,. Before TPN, and on admission tothe hospiW 1, thc patient completed the Profile of Mood States (POMS) quc,etionairc, a standardized tcstmr1l,uring depression, anger, vigor, faligue, and confusion. The patient completed the qucslionaire again atthe end of TPN near discharge. Wc scored the tests, with the best score being 100% and compared thechange from basclinc for each mood for both groups or patients.

~ n~uc irsm

improvement (+) or worsening (-) in mean (SEM) *Mann-Whitney tcst p= 0.03 control vs. glutamine

The. patients receiving the Gln-cont.’Bining solutions were more vigorous when compared to contol. TheGin group also showed improvement in other nutritional parameters: improved nitogen balance: earlierdischarge from the hospital; and Icss infcctious episodes. This is one of the first nutrition interventionsttulics to illustrate an improvement in patients psychosocial status and correlate these changes withnutritional effects. Gin may play a role in patients feelings of well-being either directly by cffccúng centralnervous system neurotransmittors or through its effects on the protein status of patients. Psychosocialtesting may prove useful in evaluating functional status of patients receiving nutritional support.

16

INTRAVENOUS ADNINISTRATION OF NUCLEOSIDES AND A NUCLEOTIDE nIXTURG JIIIINISIIESINTESTINAL HUCOSAL ATROPHY INDUCED BY TOTAL PARENTERAL NUTR I T 1 ON. S.Iijiea,hD,T.Tsujinaka,ND, Y.Kido,RD, Y.Hayashida,HD, H.)sh!dt.M[),T.Ho<t<tt,M[). N.Sakaue,hD,C.E6isui,ND, K.Kan,IBD and T.hori,HD Departvent ofSurgery II, Osakn Universitylied leal School, Osaka, Japan

Total parenteral nutrition(TPN)is associated vith atrophic changes in thestructure and function of intestinal mucosa. Since rapid growing intestinalmucosal cells require a external sourse of prines and pyri.idines,thesupplementation of nucleosides and a nucleotide mixture (OG-VI:inosine.guanosine S-.onophosphate .cyt id i ne ,ur i dine, Lhy.i d i ne.4: 4:4:3: t)duri ng TPN mayprevent the progression of mucosal atrophy.

Male wistar rats receiveing TPH for 7 days were divided into four groupsaccording to the difference of TPM regimens.Group C (n=10) received a control,regren,Croup 0(n=10)received OG-VI(2.S.lIkg/day) in addition to the control

regi8Cn.Group G(n=10) received a glutamine rich (1.28g/100.1) TPN regimencontaining almost the same amount of calories and nitrogen vith the controlregimen.Group 0+G(n=!0)receive OG-VI(2.S8g/kg/day)in addition to the glutarinerich regi8Cn.Following parameters were examined on the 8thday in the JejunalsegU8ent:total and sucosa wet weight,mucosal protein,DNA and RNA contents,disacchridase activity and morphologic analysis.

The total and 8ucosal wet weight of the jejunal segument in group 0(36.0:t:4.4.g/e..23.4:t:4.48g/c.) and group O+G (34.4:1::2.3.22.0:1::2.2) were

significantly heavier than those in group C (31.2:1::2.7.18.4:1:: 1.7).The contents ofprotein and RNA in group 0(2.5:1::0.48glc.,400:l:: 140# g/C8) were significantly largerthan those in group C(2.0:l::0.4.287:1::82).The activities of maltase and sucrase ingruop OtG(477:1:: 153n801/8g p./.ln., 73.2:1:: 1.8n.l/.g p./.in.)were significantlyhigher than that in group C(303:1::63.5.54.3:1:: 11.1).The villus height in group 0(379.4:t:48.8#8)was significantly taller than that in group C(282.2:1::46.9).

The supplirentation of OG-VI prevents the Intestinal sucosal atrophy inducedby TPN,the effect of which Is more potent than that of glutamine.

17 Peds/G.I./FatCLEARANCE OF INTRAVENOUS FAT FROM TIIE BLOODSTREAM DURING AClITEPANCREATITIS. A. P. Robin MD, FACS, M. )~,edlcr, MD, Dcpautmcnts of Surgery, University ot IllinoisCollege of Medicine and Cook County Hospital, Chicago, IL, Northwest Community Hospital, ArlingtonHcights, IL

This study was undertaken to determine the ability of paticnts with acute pancreatitis to clear exogenousfat from the bloodstream. Eight normutriglyceridemic patients with acute pancreatitis were studied. Astandard intravenous fat tolerance test (IVFIT) was performed and the fractional removal rate (K2) andmaximal clearing capacity (K1) analyzed. On the following day, lipoproden lipase activity from the deep(skeletal muscle, LPL.) and supcrficial (adipose, LPLS) tissues of the forearm wcre measured bycannulating the appropriate veins and excluding the hand from the circulation. Enzyme activity was mea-sured at baseline and every minute for 10 minutes after injection of 15 U of heparin into the brachial artery.Peak enzyme activity [P] and totii activity over 10 minutes [I] were measured in the effluent blood. Con-trol subjects (n=4 for LPL, n=8 for IVFM were studied after an ovcrnight fast. Results arc shown below.

LPLDIS in pancreatitis and control, respectively was 4.54t1.36 and 2A9±0.27 for peak and 2.93±0.77 and1.84±0.35 for total activity. There was a direct relationship between K, and K. (r=.691) and between LPLactivity and lipid clearance.

In conclusion normolriglyceridcmic patients with acute pancrcatitis do not manifest impairedintravenous fat clearance. Futhermore, skeletal muscle LPL activity is no different from controls. Slightlydiminished adipose tissue LPL activity is probably a result of the longer period without oral intake.

18

TOLERANCE OF EARLY FEEDINGS IN VERY LOW BIRTH WEIGHT (VLBW)INFANTS. L.M. Mileur, G.M. Chan, R.E. Kimura, U of Utah, Salt Lake City,UT

Hypocaloric enteral feedings have been reported to decrease the incidence of feedingintolerance in VLBW infants.Initiation of first feeding was delayed in published studies andseveral weeks were required to achieve full enteral feedings.We hypothesized that early,lowvolume feedings would improve feeding tolerance enabling earlier establishment of enteralfeedings in VLBW infants.A total of 55 infants <1200 g,<30 wk GA have completed thestudy.Criteria for study included <9G hr of life, active bowel sounds with stooling, andconcurrent parenteral nutrition support.lnfants were divided into groups by enteral feeding(Human milk or Similac Special Care -20 Kcal/oz) and randomly assigned to one of twofeeding regimens.All infants received a small amount of feeding (Ice q 4-6hrs) for the first48 hours of study.Infants were then progressed at 5% (n=27) or 15% (n=28) incrementsuntil 100 Kcal/kg/d enteralwas reached. Birthweight,gestational age,intake (Kcal/kg/d),andweight change (g/d) did not differ between groups.Days to reach 100 Kc.1l,’kg/d enteral waslonger for 5% vs 15 infants (p<.001).Feeding intolerance defined as pt.:~.,:nce of at least 2of the following:l)gastric residuals >2cc/kg, 2) abdominal distension, 3) 11~,ne positive stoolsor residuals, or 4) bowel loops. Incidence of intolerance was 20% but did not dit’fer betweenfeeding or feeding regimen. NEC occurred in 2/55 (3.5%). We conclude that 1) smallvolume enteral feeding begun within the first 96 hr of life are well tolerated by VLBWinfants, 2) daily volume increases of 5% or 15% did not influence the incidence of feedingintolerance, and 3) use of human milk or formula feeding did not increase feedingintolcrance.

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19

INTRALIPID INFUSION DECREASES GLUCOSE TURNOVER IN PREMA

TURE NEONATES. M. F. Everett, MD, M. H. Deng, PhD, and B. Caballero, MD,Ph.D Joint Program in Neonatology and Nutrition Support Service, Children’s

Hospital, Harvard Medical School, and Clinical Research Center, MIT, Boston, MA.We studied the effect of Intralipid infusion on glucose turnover in 7 AGA prema-

ture neonates (mean gestational age 32 wks [29-36 wks], mean birthweight 1.95kg [1.33-3.0 kgl, gender 5 males, 2 females). All infants were non-asphyxiatedand mechanically ventilated for uncomplicated HMD. Prior to and during the

study, infants exclusively received intravenous glucose at rates of 4.2-9.1

mg(kg’min)-I, and all had stable blood glucose levels. At a mean age of 46.3 hrs

(27-69 hrs), a primed, constant [6,6-2H2]glucose tracer infusion was started and

maintained for 240 minutes. After 120 minutes, a 20% Intralipid infusion was

started at 0.15 g(kg,hr)-i (-3.5 g(kg~day)-1). Glucose turnover was calculated from

tracer infusion rates and assumed steady-state plasma isotopic enrichments measuredat 0, 90, 120, 210, and 240 minutes.

No major change in clinical status occurred in any of the infants during the

4-hour study. Steady-state glucose turnover during the Intralipid infusion was sig-nificantly lower than during the pre-Intralipid period: 3.68 t 0.41 vs. 4.16 t 0.35

mg(kg*min)-i (p < 0.04, paired t-test).Thus, the administration of fat emulsions at rates commonly ,sed in parenteral

alimentation of premature newborns is associated with a significant decline in

glucose turnover.

20

TOTAL PARENTERAL NUTRITION (TPN) WITH SHORT-AND LONG-CHAIN TRIGLYCERIDES (LCT)REDUCES INTESTINAL MUCOSAL ATROPHY AND IMPROVES PROTEIN METABOUSM INBURNED RATS. M.D. Kartstad. PhD, J.A. Guszcza, B.S., J.W. Bailey, PhD and S.J. DBM!chole, PhDUniv. of Tenn. Med. Ctr., Knoxville, TN; Abbott Laboratories., Abbott Park, IL.

The effect of TPN supplemented with LCT and triacetin, the water soluble short-chain

triglyceride (SCT) of acetate, on structural parameters of the intestinal tract and protein metabolismwas assessed in burned rats (30% body surface area). Rats received 160 kcal’kg-1’day’1, 9.6 gamino acids’kg-1’day’1 and 30% nonprotein calories as 90% SCT/10% LCT, 50% SCT/5096 LCT,or 100% LCT for 7 d. Plasma acetate, cumulative nitrogen balance, jejunal and colonic DNA andmucosa wt (mg*10 cm&dquo;*100 g body wt-1) and DNA/mucosa (l1g/mg) are shown below.

n = number of rats; § = P s 0.05 compared to other groupsPlasma acetate was higher and nitrogen balance was substantially lower with 90°,6 SCT/10% LCT.TPN with 5096 SCT/5096 LCT promoted a positive nitrogen balance similar to 10096 LCT, resultedIn smaller and more numerous mucosal cells In jejunum and colon, and increased colonic mucosal

weight and DNA. The equicaloric provision of triacetin and LCT improved protein utilization andstructural integrity of the small and large bowel and reduced the development of intestinal mucosal

atrophy associated with conventional TPN containing 10096 LCT in burn injury.

21

IN00RPORATION OF’ ENTERAL W3 W6 AND W9 FATS INTO RAT HEPATIC SINUSOIDALPHOSPHOLIPIDS IN <4 DAYS DURING Et,DOTOXEMIA. J Palombo DSc E Lydon, KFechner BA, S Lopes BS, G Blackbum MD PhD, B Bistrii3n MD P~D, RA ForseMD PhD. Nutrition Labs, Deaconess Hosp/Harvard.Med School, Boston MA.

Enrichment of sinusoidal Kupfrer and endothelial (K&E) cell phospho-lipid fatty acids (PLEA) with fish oil ET~(20:5w3) decreases the rela-tive % of linoleic (18:2w~ and arachidonic (20:4w6) acids availablefor conversion to undesiredvasoactiveeicosanoids and cytokines afterendotoxin exposure. The study objective was to assess tF~e extent offish (w3) or olive (w9] oil vs. corn (w6) oil FA incorporated into rat~t~hp¿w~d~~ normal or ~à~t~~êmîg~oJ~Hi~~ ~iÁ~cg:R~~~~ enteralfeeding for 3.8 days. Adult rats received a basic errteral diet i.g.(220kcal/kg, 1.4 g Nfkg/day, 4% kcal from safflower oil) supplemented witheither w3 w6 or w9 oil (18% total kcal). Either saline (-ETX) or endo-toxin(+ETX)wasinfusedi.v.(0.5-lnq/kq)forthelast72hours,Hepatic K&E were subsequs~tly isolated by use of collaqenase cent n fug-ation, and w~~rï~~~~&eth;i~~~a~ ~~~i ~f~o~!a~~~~~ ~~r~~:JJ’!~~L~g!,.~-~tJ::.er TLC,~Results are ex! pressed as relative $ of total FA:

SigW ficant incorpo ration of fish oi1 FA ~t~l~E~r~~cedth~~ ofrelative % of 18:2w and 20:4w6 ol ve oil FA also decreased the of18:2w6 but not 20:4w6. Fish FA IffiY retard 20:4w6 formation. For a givendietary oil, FA incorporation into K&E PL was similar under endotoxenuc

vs. normal conditims. Plasaa PLm gattems also reflected the changesobserved in K&E PLFAT indicating that dietary modulation of endogenouslipid release from liver/gut occurs ppidly~n7be rapid incorporatirn ofdietary oil FA into IC6~E PLFA by continuous enteral feeding underscoresthe practicality and importance of this modality for pharrracologic mod-ulatlon of K&E cell structure/function pre-operatively or during sepsis,

22

WEIGHT LOSS DEPLETES ADIPOSE OMEGA-3 FAITY ACID RESERVES. SD Phinney,AB Tang. Div of Clin Nutr, Dept of Med, Univ of Calif at Davis, CA

The balance between highly unsaturated metabolites of omega-6 (w6)and omega-3 (w3) fatty acids (FA) is important in the regulation ofinflammation, immunity, and hemostasis. These 20- and 22-carbon

products can be produced endogenously from linoleate (13:21016) and alpha-linolenate (18:3w3). Adipose tissue (AT) contains major reserves of boththe former at 10-20~ and the latter at 0.5-1.O,K. Ornega-3 deficiencyoccurs in children and adults, and can be prevented by an intake of 0.5-1.0 energy as w3 FA; but the balance of w6 and w3 FA in AT after wtloss has not been determined. We performed needle biopsies of sub-cutaneous AT before and after major weight loss by very low caloriedieting. Four groups of women have been studied on food or formuladiets providing 420-660 kcal per day with 20-2000 mg/d of 13:3w3:&dquo;

&dquo;n&dquo; ~I of subjects, I p <0.05, II = p ~0.01, *** = p< 0.001We conclude that wt loss depletes AT 18:3w3 (but not 18:2w6) despitesupplementing the former to as much as 1.0~ of daily energy expenditure.As adipose FA equilibrate with other tissue FA pools, the resultantimbalance could alter white blood cell and platelet functions inpatients with marasmus. The w3 fatty acid requirement for repletion tooptimum cellular function following weight loss deserves careful study.

23EL r’EGT OF Fiai OIL ON GUJOOSE METABOLISM IN THE INTERLEUKIN-1ALMA(IL-1) TREATED RAT. P(2 Ling t4D, N_ Istfan tID, PhD, E Colon fY~, 13Rjistrian I,n P11D. hutritia>/Infectia; Laboratory, New England Deacotiessllosi?itpl, I!~rvard ¡’¡t:d~&oelig;.l School, Boston, MA _ _ -. -

’i’his stody assessed wt>etper tlsh oil_teecjncj could nrJdif~ t1>e

rcsponse of 91gcosc ineteioolism ~~s7L~t1i~~1~.c~t~ ~td~:t3Ö~~retin~1~1 for five ¥0;~~ ~~~i~â~~i~h)crl~i~~n~ ~~r~~4ö1í (~~dffioil(sa/w) cnith 0.5,E soy bsan,oil(Fish)g or 15 a soy b~n oil(3oy~. coo-Rats receivvd IV infusims either 0.I z of albumin xaline(E) or con-tainintj IL-I(IL-I) for 3 hours; 10 gj/kj of IL-I was qiv<o as a oolusand 10 ug/kg wao continuously jnfus . he_effects of IL-I and diet mglucose metabolism were determined by a primed constant in[usioo of D-(b-3-H)qlucoscandD-(U-14-C)c]lucose for 2 hours Pla snu levels of¿r~~~~~1~)c~~3 iiisulin(I), inergy exi><1diture(EE), respiratory quotie-nt (R(2) and th,&dquo; rote of carbon recyclll19 ¡RQ~) were determined. ’1’l1e 1fr-c«itaqe cgrbchjdmtc caitmbution fpom indirect c<lorimetry(CCj a»contribution o qlucose to EE from isotope data(CI)_were calculated.

l’1l£ln+Sr.:,J.: P<UjU5WisVvssoyj b: P<V.Vb s vs iL-J; c: P=u.Vb b’isn vs

Joy; d:P<0.05 interaction by diet and treatment: f: P<0.005 S vs

IL ~ all by_two way ANOVA, e: P<0.05 L’ish-IL vs Soy-IL by,t-test.IL-I¿-11~ibYi~Y~~11yA~~êa~~P~o¿g&eth; ~~~-~~fî~î~gI~r~ti~~~~st.I -I significant oil increasos I and I cmfirciing previousfindin~s..ith fish oil fczdinq G and I pere significanjly_lpw;;rjBlhil2 the contribution of olucose oxidation to EE was ~i9m fican£1yhigher, indicating more ef~ective 9lur_oregulatory insulin action, urfindings provide evidence that fish oil feeding may improve glucoseutilizotion during infectim and inflamnatim.

24

ABSTRACTWITHDRAWN

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25 Metabolism II

BIOSYNTHETIC HUMAN GROWTH HORMONE ATTENUTATES MUSCLE PROTEINCATABOLISM AND IMPROVES WHOLE BODY NITROGEN ECONOMYPOSTOPERATIVELY. F Hammarqvist, C Strömberg, A von der Decken, E Vinnars, J Wernrrman.Departments of Anesthesiology & Surgery and Metabolic Research Laboratory, St. Gbran’s Hospital,Karolinska Institute, Stockholm, Sweden.

Background: Muscle protein loss postoperatively may be determental for patients unable to coop withsuch losses. Administration of human growth hormone (HGH) to postoperative patients has beenshown to improve nitrogen balance. The aim of this study was to elucidate the effect of biosynthesticHGH on protein metabolism in skeletal muscle and on whole body nitrogen economy after electivesurgery.Methods: Patients undergoing elective cholecystectomy were studied as a reproducible human model oftrauma. Postoperatively total parenteral nutrition including 135kJ /kg bw/24h isocaloric amounts of fatand carbohydrate and crystaline amino acid solution corresponding to 0.2 gN/kg bw/241> was given.Patients were randomized to receive daily injections of 0.3 U HGH/kg bw or saline. Percut.neousmuscle biopsies were taken from the quadreiceps femoris muscle preoperatively and 3rd postoperativeday. The state of muscle protein rynthef~~ was assessed by the concentration of size distribution ofribosomes. Muscle free amino acids were determined and nitrogen balance was calculated.Results: The total concentration of ribosomes(-18.6 ± 7.8%; p <0.05) and polyribosomes (-25.1 ± 8.9%;p<0.01) decreased in the control group whereas in the HGH group these parameters stayed unaltered.Free glutamine dropped by -33.7 + 5~6% (p<0.01) in the control group while the decrease was less

pronounced (p < 0.01) in the control group (-19.1 ± 3.2%). Cumulated whole body nitrogen balance wasnot different from 0 in the HGH-group (-2.32 ± 1.66 g N) but negative in the control group (-7.09 j:0.71 g N; p<0.01).Conclusion: The otherwise obligatory declines of protein synthesis and glutamine in skeletal musclewere counteracted in the group treated with biosynthetic human growth hormone. The effect of HGHon.skeletal muscle protein metabolism may explain the nitrogen saving effect of HGH postoperatively.

26EFFECT OF INSULIN-LIKE GROWTH FACTOR I(IGF-I)ON PROTEINMETABOLISM IN RAT. K.Okatlura,MD. Izumi City Hospital,Kagoshima, Japan

The aim of this study was to investigate the effect of

IGF-I on protein metabolism in rats with hypocaloricintravenous feeding. Eighteen rats with SVC cannulation were

divided into 2 groups. Group-I (n=ll) received no IGF-I.

Group-II (n=7) received 0.5mg/day of ICF-I for last 2 days.Isuealoric, isoui I.rogenous glucose/amino acids (NPC:91kcal/ /kg/day, N:0.55g/kg/(Iay) wt·re infused for 4 days. Urine was

collected in last 2 days for total nitrogen and

3-methylhistidine (3-MH) determination.Results:

f.rnun-i I f.rnnn-IT T

Values were mean t SD and compared by Student’s t-test

Conclusion: IGF-I remarkably improves nitrogen balance

mainly dU~: Lo reduction of protein breakdown.

27

NUTRITIONAL REGULATION OF INSULIN-LIKE GROWTH FACTOR-1 AND INSULINRECEPTORS IN RAT JEJUNUM. T.R. Ziegler MD, RJ. Smith MD, Joslin Diabetes Ccnter,llarvurd Medical School, Boswn, MA.Receptors for insulin-like growth factor-I (IGF-I) and insulin are present in rat intestinal mucosa;

however, factors which regulate these potential modulators of gut growth and repair are unknown. Thisstudy determined whether specific receptor binding of insulin and IGF-I in rat jejunum is regulatedby nutrient availability. Adult male Sprague-Dawlcy rats (280-300 g) were maintained on oral rat chow adlibitum (control), fasted for 72 hours (fasted) or fasted for 72 hours and then refed ad lib chow for 24 hours(refed). At sacrifice, total jejunal membranes were prepared (proximal 40 cm) by differential cenuifugation.Specific binding sites for IllS Ltbclecl IGF-I and insulin in jejunal preparations were idcntified withstandard binding displacement and competition iechniques using centrifugation to separate bound from freehormone after 16 hr incubation at 4 C. Specific binding was determined by subtracting nonspeciGc binding(determined with 10-7 M IGF-I or 10-6 M insulin) from total binding. Binding was linear over a range ofprotein concentrations for exh ligand. A portion of the binding data for jejunal preparations obtainedduring each nutritional state is shown (mean f sem expressed as cpm J 200 11& total membrane protein).

-

p < u.u~; --

p < U.Ul vs Control Dy ANUVA ( uunnett test T P p < U.LX)3 Insulin vs lür-l ( t-test )Following fasting for 72 hours, specific binding of both IGF-I and insulin increased by 70%. Insulin

binding was significantly greater tttan IGF-I binding during ad lib feeding and following the 72 hr fast.After 24 hours of rcfeeding, binding of both hormones returned toward control values, with a greaterdecrease in insulin versus IGF-I binding. We conclude that IGF-I and insulin receptors in rat jejunum areregulated by nutrient availability. In order to understand the interactions between specific nutrients andthese two anabolic hormones, it will be important to investigate receptor expression and receptor functionas well as hormone concentrations.

28

EFFECT uF HUMAN GROWTH HORMONE (CH) ON PROTEIN METABOLISM INRATS WITH ENDOTOXIN INFUSION. H.Koga,MD, K.Okamura,MD,Y.Horichi,MD, T.Okuma,MD, Y.Miyauchi,MD. Dept.of Surgery,Kumamoto University, Kumamoto, Japan

inis smuy was VDIIUUCLEU LO evamace cne elleel 01 lJn on

protein metabolism in stressed state induced by continuousinfusion of endotoxin. Fifty-one rats with SVC cannulationwere assigned to one of 6 groups and maintained on TPN for 4

days. Endotoxin was administered in Group-1,11,111 withdoses of 0.1,2 IIIg/100gBW/day. Each group was divided into 2

subgroups (a & b) . Subgroup-b received 200mU/day of Gli.Cumulative N balance of last 2 days and whole body proteinturnover using &dquo; N-glycine were measured.

&dquo;&dquo;,.&dquo;&dquo;&dquo;° r’~&dquo;.’’’’’’’’’~’ ---- ---- ---- ---- .......

N balance and protein synthesis rate in subhroup-b wassignificantly higher than in subgroup-a in each group exceptfor Group-III. Protein breakdown rate did not differsignificantly between subgroup-a and -b in each group.Conclusion: Nitrogen sparing effect of GH is attenua..2d as

degree of the stress advances.

29

ADDITION OF GLUCAGON TO LIPID-FREE TOTAL PARENTERAL NUTRITION (TPN)REDUCES PRODUCTION OF PROSTAGLANDIN E2 (PGE2) BY STIMULATED SPLENIC

MACROPHAGES. O. Zamir,MD, M.S. Nussbaum,MD, C.K. Ogle,PhD, T.

Higashiguchi,MD, J.A. Frederick,MD, S. Bhadra, MD, J.E.Fischer, MD.Deptartment of Surgery, University of Cincinnati, Cincinnati, Ohio.

Sepsis is a major complication of TPN. Impaired immunity has beensuggested as responsible for TPN-related sepsis, but it is unknown howthe immune system is affected by TPN. We recently found that adminis-tration of lipid-free TPN resulted in an increase in PGE2 release bystimulated splenic macrophages. This observation suggested that TPN mayimpair immunity through prominent immunosuppressive effects of PGE2. In

the present study we tested the hypothesis that addition of glucagon toTPN solution may protect against the immunosuppresive effect of TPN bymodifying lipid metabolism. Adult rats (n-18) underwent jugular veincannulation: Group 1 (n-7) IV saline + chow ad lib;Group 2 (n=6) TPN 80

ml/24h;Group 3 (n=5) TPN + glucagon (100 gg/24 h).After 10 days spleenswere removed and splenic macrophages were isolated and cultured for 24hin plain M199 media (nonstimulated) or in media containing E.Coli LPS 5I1g/ ml (stimulated). PGE2 release was determined by ELISA.

GROUP 1 GROUP 2 GROUP 3

PGE2 Release Nonstimulated l.S1t0.69 4.27:L3.73 0.49:!:0.31

(ng/2.5 x 106 cells) Stimulated l6.04:!:3.26 81.68t25.99* l5.n:!:3.33

Results are meantSEM; *P<0.02 by Tukey’s test following ANOVA.The results confirm that TPN may be immunosuppressive through the

release of PGE2 by stimulated splenic macrophages. Addition of glucagonmay prevent this adverse effect of TPN.

30

HEPATIC UTILIZATION OF EX&OElig;El-PUS ADENINENUCLB3TIDE PREA)RSORS FORRESTORATION OF ATP FOLLOWING EXTENDED ISCHEMIA. J Palombo DSc J BowersPhD, M Clouse MD, A Forse MD PhD, B Bistrian MD PhD. Depts, of Surgery,Radiolociv. and Medicine, Deaconess HospAiarvard Med School, Boston, MA.

ATP in pö5tischemic or &dquo;b:ansplanted liver is retarded byATP and release of membrane-permeablefurine metabolites. Given that purine synthesis de novo 1S slow andATP dependent postischemic liver can become dysfunctional secondary toinadequate cellular ATPcontent. The theeffects of adenosine (ADO) or adenine(ADN) supplementation on ATPrestoration in perfused rat liver after co ischemia. Fresh liversfrom 18 fed SD rats weceharvestedandperfusedportally with oxygen-ated Krebs’ buffer (37’C) to determine baseline ATP cm tent using &dquo;PNMRspecttaoft.heB-ATPpeakatl21.6hHz. Liverswere then flushedand stored in Univ. Wisconsin solution for 18 hours at 4°C. All liverswere then reperfused with oxygenated Krebs to assess ATP recovery by lipU1R. After 30 min. reperfusl en, 12 livers were co-infused with eitheror Six other livers served as controls. ATPrestoration as a %<MFan+SD)nf the orest-craae baseline level was:&horbar;&horbar;&horbar;&horbar;

Initial ATP recovery had scapm zea aurmg tne m rsc ju mm .Mperfusion and was <65 of prestorage baseline, ATP restorationduringfe subse~umt 90 mip, co-infusion was significantl( greaterwith ADO than ADN. These differences were presumably due to theefficiency of adenosine kinase vs. potential product inhibition ofadeninephosphoribosylnansferase. HPLC analysis of theeffluents ofADO-infused livers revealed <0.5% degradation to uric acid. Thus.MOand, to a limited extent, ADN are conditionally essential nutrientsrequired by postischsnic liver to rapidly and for ADO, fully restoreATP. Other splanchnic organs (gt) with limited de novo capacity mayalsobenefit from ADO supplementation after ischemia. The importance ofthis is underscoredbytheabsence of ADO or ADN in an feral products.

of

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TIIE INFLUENCE OF CHRONIC, LOW-DOSE INFUSIONS OF RECOhIBINANT HUMANINTERLEUKIN-1 AND TUMOR NECROSIS FACTOR -ON PROTEIN METABOLISM.J.H. Schwartz, MD, EJ. Colon, BS, N.W. lstfan, MD, PhD, and B.R. Bistrian, htD, PhD Departmentsof Surgery and Medicine, New England Deaconess Hospital, Boston, MA.The development of the recombinant human monokincs interleukin-l (rhIL-1) and tumor necrosis

factor (rhTNF) now enables researchers to reproduce the acute-phase response in intact, nonscpticlaboratory animals. We recently studied the nutritional dynamics of this phenomenon using radio-labelled traccrs to estimate independently thc relative rates of protein synthesis and degradation inlivcr and muscle, and the rate of appearance of glucose in the plasma (glucose Ilux). Healthy maleSpraguc-Dawley rats (2511-300 gm) were continuously infused for 6 days with rhIL-1-a, 20 ug/kg/day,rhTNFa, 100 ug/kg/day, or a combination of rhIL- li~, 10 ug/kg/day and rhTNF-o, 50 ug/kg/dayi.v., and compared to an ad lib., saline-infused control group, and to a second saline-infused grouppair-fed to the average daily consumption of the anorexic, monokinc-treatcd animals. On day 7 allanimals undcrwent protein and glucose turnover measurements by continuous infusion of 14C-lcucincand 311-D-glucose tracers. Fractional and total synthesis rates for hepatic structural proteinsignificantly decreased (30%, P< 0.03 by ANOVA) in the IL-1-treated rats only, but iiver breakdownrates were markedly diminished (25-50%, P < 0.001 by ANOVA) in all monokinc-treated groups.Thus, the ratio of synthesis to breakdown, the anabolic index, was > 1 in the monokine-trlOatlOüanimals, reflecting an increase in hepatic structural protein mass despite decreased protein intake. Theratio of synthesis to breakdown ratc in muscle was significantly < 1 in the monokine-treated animals

(P < 0.003 by ANOVA), suggesting net muscle protcolysis. Glucose nux was significantly elevated 1>yIL-1 or by IL-I/TNF coinfusion (P < 0.04 by ANOVA), but not by TNF infusion alone. The dr.tmatiereduction in hepatic structural protein degradation rate represents a novel cnergy-cffieient mechanismfor the maintenance of hepatic structural mass in the setting of decreased dietary intake thataccompanies critical illness. While both IL-1 and TNF induce mobilization of amino acids fromperipheral muscle stores, TNF appears to promote net augmentation of hepatic structural protein,while IL-1 may be more influential in directing amino acid precursors towards gluconeogenesis.

32

PROTEIN SYNTHESIS RATE IN HUMAN SKELETAL MUSCLE IS UNAFFECTED BYANESTHESIA BUT DECREASES AFTER SURGERY IRRESPECTIVE OF TOTALPARENTERAL NUTRITION. P. Essdn, MD, M. A. McNurlan, PhD, J Wemerman. MD, PhD, P,J. Garlick, PhD. Depts of Anesthesiology and IC at Huddinge University Hospital, St Gomn’sHospital, Karolinska Institute, Stockholm, Sweden, and Rowett Research Institute. Aberdeen, UKSeveral components contribute to the stress imposed by surgery. This study was undertaken to

assess the separate impact of anesthesia, surgery and postoperative nutritional on proteinmetabolism in man. We have recently developed the flooding dose technique employing(1-13C)Ieucine for assessing protein synthesis in human muscle. The method is appropdate for thistype of investigation, since it enables rapid and sequential measurements.Protein synthesis in muscle was studied in four groups of healthy patients undergoing abdominal

surgery. The basal determination of muscle protein synthesis was performed in the postabsorptivestate. The second assessement was perfomied during anesthesia (n=7). immediately after surgery(n=7), and three days postoperadvely in patients receiving saline only (n=8) or total parenteralnutrition.For each measurement of muscle protein synthesis rate percutaneous biopsies were takenfrom the quadriceps femoris muscle before and 90 min after an intravenous injection of (1-«C)leucine (0,05 g/kg. 20 APE). The rate of muscle protein synthesis was calculated from theincrease in enrichment of leucine in protein during the 90 min period, using isotope ratio massspectrometry. The enrichment of plasma a-ketoisocaproate was used to indicate the enrichment ofthe precursor for protein synthesis and analyzed by gas chromatography mass spectrometry.Protein synthesis rate was unaffected by general anesthesia alone ( 1.97 t 0.18 v. 2.01 t 0.18;

NS). However, surgery, in the form of cholecystectomy, resulted in a rapid decrease in proteinsynthesis from 2.17 t 0.07 to 1.55 t 0. i5 (p<0.01). When the effect of surgery was combinedwith three days of postoperative fasting, the rate of protein synthesis declined from 2.34 t 0.13 to1.31 t 0.18 (p<0.01). Maintenance of adequate nutrition in the three-day postoperative period byTPN, however, did not alter the decline in protein synthesis.(1.98 ± 0.07 v.0.91 t 0.14; p<0.001)In summery, the immediate response in muscle protein synthesis rate to surgery was rapid andsubstantial. The decline was still apparent after three days irrespective of postoperative nutrition.

33 Young Investigators «

THE EFFECTS OF GROWTH HORMONE ON MUSCLE ENERGETICS DURING SHORT-TERM I

STARVATION. T. Kobayashi, MD, V.Robinson, AS, D.Wllmore, MD, and D.Jacobs, MD. Department of I

Surgery, Harvard Medical School, Boston, MA. I

Growth hormone (GH) Improves nitrogen retention In catabolic patients. To dotv..,1ine its effects onmuscle energetics, in vivo 31p magnetic resonance spectroscopy studies of the gast~ocnemius musclewere performed in male Wistar rats (188t1g) fed a nutritionally complete liquid diet (CONTROL,n=7), or fasted for 4 days with (+GH, 5trg/gBW sc, BID, n=11) or wdhout GH (-GH, n=11). CONTROL and -GHrats received a daily placebo injection. All rats were allowed water ad lib. Urine was collected daily forbalance studies ( nitrogen (N), phosphorus (P), potassium (K), sodium (Na), and water). Spectra wereobtained at baseline, 2 and 4 days after fasting using a surface coil In a 8.45 Testa magnet. Phosphateratios, intracallular pH, and the break down rate (only on day 0 and 4) of the high energy storagecompound phosphoaeatine (PCr) were determined. Tissue ATP levels and total creatine kinase (CK)activities were measured s~ctrophotometncally. A portion of data is shown (mean t semI.

1 -.... 1- ..-..--. 1 -- ..-- I -- L ... I

groups WithOut matching letter are signdtcandy different (p<O OS) by ANOVA & Tukey post hoc (f1gig wet we¡ghVsec)+GH rats lost 15 % less weight than -GH in association mth 13 % greater ndrogsn retention and

increased P, K, Na, and water balances. ATP levels and CK activities were sirniar in all groups. PCr/ATPwas significantly lower In +GH after 2 days fasting secondary to increased consumption of PCr. while pHdecreased in -GH at this time point (7.1510.01 vs 7.19t0.Ot, -GH vs +GH, p<0.05). PCr breakdown rates

were similar in CONTROL and +GH but higher In -GH indicative of a decreased need for ATP synthesis viathis route. Thus, during acute fasting GH admimstrauon improves ndrogen balance and allows moreefficient use of peripheral energy stores. This effect may be mandested as a greater ability to increaseATP synthesis Irom PCr breakdown when energy demands increase, e.g , during muscular contraction.

34

EFFECTS OF GROWTH HORMONE IN POSTOPERATIVE PATIENTS ARE NOT DOSEDEPENDENT. H. Sa~o, MD, K. Tanrvvaka, MD, H. Hashiguchi. MD, S. Naka, MD,Kuroiwa, T. Sawada, MD, T. Muto. MD Department of Surgery, Umversify of Tokyo, JapanExogenous growth hormone (GH) increases insulin-like growth factor 1 (IGF-1) and

produces nitrogen retention during surgical stress. However, the effects of the GH doseon protein metabolism after surgery remain unclear- We have studied the effects of GHtreatment on protein and mineral metabolism in postoperative patients receiving twodifferent doses of GH. Nineteen patients having colectomy were divided into threegroups. Daily Intramuscular injections of GH were given to Group 2 (0 2 u/kg) and 3 (0.4ulkg) for 6 postoperative days, while Group 1 received no injection. All groups received20 nonprotein kcavkg and 150 mg n4rogeNkg daily.

There were no differences in nitrogen and mineral metabolism between the group whichreceived 0.2 u/kg of GH and the group which received 0.4 u/kg of GH.These results suggest that exogenous GH improves protein and mineral metabolism

after surgery. However, the dagree of GH-induced improvement is independent on theGH dose given. We conclude that daily injection of 0.2 unitlkg may be enough to achievethe beneficial effects of GH treatment in postoperative patients.

35

PREOPERATIVE CARBO11YDRATE SUPPLEMENTATION REDUCESPOSTOPERATIVE DEVELOPNIENT OF INSULIN RESISTANCEO. Ljungqvist MD, PhD, A.Thorelt,l.lD, S. Efendic MD,PHD* & M.Gutniak MD,PHD’Departments of Surgery & ’Endocnnology, Karolinska Hospital & Institute, 104 01 Stockholm,Sweden

Ovemight fasting is usually applied before elective surgery Any influence by this procedure onmetabolic responses to sufgery has not been questioned. However, this shon fasting perod reduceshepatic glycogen, and changes body metabolism. Animal studies indicate that already short termfasting has marked influence on hormonal and metabolic responses to sues&dquo; and has been associatedwith increased monality in experimental suess. Presently, the effect of carbohydrate maintenance byglucose infusion (5 mg/kgJmin) iv during preoperative fast on insulin resistanct after uncomplicatedelective cholecystectomy was invesugated, and related to eoncomillallt hormonal alierauons.Mdhods. 13 patients (11 women, 2 men) were randomly allocated to preopcrative fast with (n = 6)or without glucose infusion (n = 7). Insulin sensiuvity was determined using hyperinsulinemic eugly-cemic clamp techniques before and on the 1st post operative day. Glucose utilisation (M-value) wasexpressed as mg/kg b.WI./mln.Values are mean ± SEM, differences calculated using non parametrictests.

Results. There was no difference In age, body mass index, sex, operative procedures, or preoperativeM values between the two groups. Cholecystectomy after uncompensated fasting reduced M valuesfrom 4.3 t 0.4 mg/kg/min to 2.0 0.2 nlg/kg/mill, (-53~90, p < 0.01). Prc-ueatmenl with glucoseinfusion resulted in a significantly less pronounced reduction in insulin sensitivity (-32°k) aftersurgery compared to uncompensated preolxrative fasting, p < 0.01. No major differences in insulin,glucagon, cortisol or catecholamine levels werc found between the groups on the day after surgery.Conclusion. Compensation for carbohydrate reserve depletion with glucose infusion during fastingbefore surgery markedly improves post operative metabolic state of patient even after uncomplicatedabdominal surgery. By reducing metabolic stress, this procedure may prove beneficial for recoveryafter surgery.

36

IN VIVO DETERMINATION OF THE RELATIONSHIP BETWEEN AMINO ACID TRANS-MEMBRANE TRANSPORT AND PROTEIN KINETICS IN MUSCLE. * G. Biolo, MD,D.Chinkes, MS, X.J. Zhang, MD, and R.R. Wolfe, PhD. Shriner. BurnsInatitute and University of Texas Medical Branch, Galveston, TX.

The bidirectional trane-membrane transport rates of leucine (leu),valine (val), phenylalanine (phe), lysine (lys) and alanine (ala) weremeasured in vivo in the hindlimb muscle of 5 dogs and related to therates of protein synthesis and degradation. The compartimental model wasbased on the systemic continuous infusiori of stable Isotopic tracers ofthe amino acids, and the measurement of the enrichment and concentrationin the arterial and femoral vein plasma and in the intracellular freewater in muscle (obtained by biopsy).

Results, the transport rate from plasma to tissue (¡;mol/min) was: leu:IS.lil.8, val: 26.9:1:3.5, phe: 10.5il.6, lyB: 12.2:1:1.8, ala: 10.1:1:3.4. The

transport from tissue to plasma (pmol/min) was: leu: 25.5*2.5, val:

32.4*2.8, phe: 11.0:1:2.8, lYB: 24.9:1:3.4, ala: 34.4:1:9.0. When thetranamembrane transport rate was normalized per unit amino acidconcentration in the source pool we found that the transport of leu, valand phe was significantly faster (p<0.05) then the transport of ly. andala. The calculated rates of incorporation into hindlimb muscle groteinof phe and lys (/-Imol/min) were 4.2*1.3 and 19.4:1:5.3, respectively, andthe rates of intracellular appearance from breakdown were 10.1:1:1.9 and

32.1±6.6, respectively.In conclusion. 1) the tranb-membrane amino acid transport rate can be

measured in vivo in muscle with a relatively non-invabive technique; 2)in the dog hindlimb the equilibration between tissue and plasma freeamino acid pool is different for each amino acid depending on thekinetics of the trans-membrane transport systems; 3) the transport ratesof amino acids and their rate of appearance from protein breakdown areroughly comparable, suggesting that variations in transport rates couldplay a role in controlling the rate of protein synthesis.

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37

IMMUNOLOGIC DYSFUNCTION INDUCED BY CHRONIC ETHANOL INTAKE ISGUT-MEDIATED. L.M. Napolitano MD, MJ. Koruda MD, K. Zimmerman MS. K. McCowanBS, A.A. Meyer MD PhD, Depanment of Surgery, University of North Carolina, Ctwpel Hill,North Carolina.

Chronic ethanol (EIOH) intake is associated with increased susceptibility to infection in thehost. This study examined whether immune alterations induced by chronic EtOH intake weredependent on enteral (PO) administration. SD rau received 2096 EtOH daily for 14 days bygavage (PO) or SVC infusion (IV). Mean blood EtOH cone. at 90 min were 95.3mg/dl(PO)and 94.4mgldl(IV). Nonadherent splenic lymphocytes were tested for mitogenie responses toconcanavalin A (ConA), phytohemaglutinin (PBA), lipopolysaccharide (LPS) and pokeweed(PW) mitogcns. Quantitative cultures of mesenteric lymph nodes and liver were alsopedormed. PO EIOH intake induced a significant impairment in milogenic response to T-cellmilogens with a 4-fold reduction in Con A and a 2-fold reduction in PIlA response (p < 0.05 byANOVA) and increased translocation. Chronic EIOH administered by the IV route did notreduce mitogenic response to any of the !2~~e_~~.!~~~icd.

- . ----.. -

(Data expresxd as Mean(SEM), Stimulation Index = CPM mitogen/CPM no mitogen)Enleral but not IV administration of EL01i induced significant immunologic dysfunction,

demonstrated by altered T-cell mitogenic response. These results suggest that this ethanol-induced reduction in immunocompeteiice is gut-mediated.

38

SELENIUM RENAL HOMEOSTASIS IS IMPAIRED IN PATIENTS RECEIVING LONG TERMTOTAL PARENTERAL NUTRITION. A.L. Buchman, M.D., A. Moukarzel, M.D., Ph.D., M.E.Ament, M.D. Department of Pediatrics. Division of Pediatric Gastroenterdogy/Nutrition,UCLA Medical Center, University of California, Los Angeles, 90024-1752 and Division ofDigestive Diseases, Emory University Schod of Medicine, Atlanta, GA 30322.

Selenium deficiency has been reported previously In patients receiving long termTPN without selenium supplementafion in their solutions. The RDA for selenium is 0,87mcg/kg of which 80% is absorbed. We studied 30 adult long term TPN patients aged 21-79years (x = 51.2-:L3.0) who have received TPN for 8.3 + 4.4 years. They receive 40f0 mcgof selenium daily in their TPN. True GFR was measured by indium 111-DTPA clearance.Tubular function was measured by the tubular reabsorption of phosphate (TRP). Serumand urine selenium levels were measured by atomic absorption. Blood for selenium wasobtained from each subject’s Hickman catheter using a metal free syringe. Urine wascollected for 24 hours in nitric acid washed containers. 22/30 patients (68%) had lowserum selenium levels (mean: 72.9 ± 12.2; normal 95-165 ng/dl). Of the patients with lowserum selenium levels, 15 (73%) had elevated urinary selenium losses (mean: 55.6 ± 15.6;normal < 36 mcg/dl). However, no significant correlation between serum or urine seleniumlevels and GFR or TRP was observed. We conclude that the previously described renalhomeostatic mechanism for selenium conservation may be significantly impaired in patientsreceiving long term TPN. Such patients may require much greater doses of selenium thanpreviously recommended. Therefore patients on long term TPN should have their serumselenium level monitored despite daily selenium supplementation.

39

INTERLEUKIN-4 REDUCES CHEMICALLY-DEFINED DIET (CDD) INDUCEDBACTERIAL TRANSLOCATION IN MICE. J. Shou,MD, E. Minnard,MD,L.Motyka, PhD, J.M. Daly, MD. Dept of Surgery, University of Penna, Phila, PA

Administration of a CDD results in bacterial translocation (BT) which is associatedwith impaired macrophage antimicrobial functions. This study evaluated the effectsof interleukin-4 (IL-4), which upregulates macrophage functions, in preventing CDD-induced BT. Balb/C mice (n=75) were pair-fed either regular chow diet (RD) orCDD for 7 days at which time animals entered three groups: RD, CDD andCDD+IL-4 30,000u/mouse ip. Mesenteric lymph nodes (MLN), liver, spleen andcecum were quantitatively cultured. Ileal mucosa was sampled for protein. Peritonealmacrophages were harvested for superoxide anion (Q¡-) production and Candidaalbicans phagocytosis (CAP) and killing (CAK).

MeantSD; *pCO.OS vs RD;’’p<O.OS vs CDDOral feeding of a CDD results in intestinal atrophy and bacterial translocation.

Administration of IL-4 had no trophic effects on the intestine, but signiticantlyupregulated macrophage functions. IL-4 significantly reduced positive MLN in CDD-fed mice and may be beneficial in reducing the incidence of gut derived infection.

40

PARENTERAL GLUTATHIONE MONOESTER ENHANCES TISSUE ANTIOXIDANT STORES.MK Robinson, MD, MS Ahn, AB, JD Rounds, BS, JA Cook, PhD*, DW Wilmore, MD. Dept. ofSurgcry, Harvard Medical School, Boston, MA and * Radia6on Oncology Branch, NCI, Bethesda, MD.UlutaUuonc (GSH) is a potent endogenous anllo;udant wtuch proteels major organs trom oxlclani

injury but present nutritional regimens may inadequately support fissue stores of this tripcpùde duringcritical illness. To determine if GSH reserves can be enhanced in vivo with iv supplements, male Wistarrats (219-+l gms) underwcntccntr.¡1 venous caÚleterization, were given chow and water ad lib during atwo-day recovery period, and were then randomized to receive one of three treatments as an iv bolus: 1)dextrose 7.5 mmollkg (DEX, n=12), 2) GSH 5.0 mmol/kg (GSH, n=12), or 3) glutathione monoclhylester 5.0 mmol/kg (GSH-ME, n=l 1). GSti-ME is transported into cells more easily than GSH. Liver,ileal mucosal and plasma samples were analyzed for GSH at 2 and 4 hours after drug administration.Results are shown as meanisem.

.p<O.05 vs DEX by ANOVA or Kruskal-Wallis

Liver GSH was signiGcantly increased by 47% in the GSH-ME rats at 2 hrs compared to DEXanimals and remained elevated at 4 hrs. aSH-ME animals also had a greater than 20% elevation of ilealmucosal GSH at 2 and 4 hrs and a dramatic increase in plasma GSH at 2 hrs. In contrast, livcr GSH wasunaltered in animals receiving GSH at 2 hrs and was reduced by 25% at 4 hrs compared to the DEX rats.GSH administration did not significantly affect mucosal or plasma GSH concentration at the time pointsstudied. We conclude that : 1) the monoethyl ester of glulathione can be used in vivo to enhance tissueand plasma GSH concentration and 2) intravenous glutathione administration does not significantlyincrease liver, mucosal or plasma GSH levels and may paradoxically depress hepatic GSH. Since themalnourished and critically ill are likely to have depleted GSH stores, nutritional strategies that includethc provision of GSH monoester may lend additional support to those organs that arc frequently exposedto increased oxidative stress during catabolic states,

41

GLUTAMINE ENHANCES CELLULARITY AND FUNCTION IN THE TRANSPLANTED SMALLBOWEL.W Frankel, MD, W Zhang, MD, J Afonso, MD, D Klurfeld, PhD, S Don,BA, D Deaton, MD, A Naji, MD, PhD and J Rombeau, MD, Harrison Dept.Surg. Rei3. Univ. of PA., Wiatar Inst., Phila., PA.

TPN is required by all patients in need of small boweltransplantation (SBT). TPN produces gut atrophy and hypofunction.Glutamine (Gln) is the preferred enterocyte fuel. The purpose of thisstudy was to determine: 1) if Gln enhances cellularity and absorptionof the SBT and 2) the optimal route of Gln delivery (parenteral vadirect infusion into the SBT). Lewis rate underwent SBT and werealimented with TPN. Catheters were inserted intravenously and into theSBT for infusion of either 2% Gln or an isonitrogenous, isovolemicmixture of non-essential amino acids (control) for 14 days. On day 14,’4C glucose absorption (&dquo;CAb) was determined by continuous perfusion inan in-vivo segment of the SBT, and mucosal protein and DNA content weremeasured.

3E±SEMSBT Infusion Parenteral Infusion

Control (N&dquo;8) Gln (N=6) Control (N=5) Gln (N=5)&dquo;CAb (J.lg/cm2/hr) 1.34tO.14’ 2.00tO.16b 1.40tO.11’ 1.78tO.23’&dquo;Protein (mg/cm) 1.7610.l4’ 1.94:10.05&dquo;&dquo; 1.05tO.13’ 2.39tO.384DNA (J.lg/cm2) 81.73i:l2.86r 101.0lt11.61’ 67.03i:l5.16’ 93.OSt11.67~Values with unlike superscripts are significantly different (p<0.05) byprotected least significant differences test.Values with like superscripts are not significantly different.

Infusion of Gln into the SBT significantly increased 14CAb comparedwith SBT controls. Parenteral Gln significantly increased SBT mucosalprotein content compared with parenteral controls. Parent&dquo;ral Glnenhanced &dquo;CAb and cellularity equal to direct infusion of Cln into theSBT. These results provide a rationale for investigating Gln-supplemented TPN in patients with SBT.

POSTER PRESENTATIONS42 Protein/ArginineUSE OF y-L-GLUTAMYL-L-TYROSINE TO PROVIDE TYROSItJE IN TOTAL PARENTERALNUTRITION IN RATS. P. Radmacher, BS, M. Hilton, PhD, F.Hilton, ScD,S.Duncan, MD, O.Adamkin, 14D. Depts. of Biochemistry, of Anatomy andNeurobioloqy, and of Pediatrics. University of Louisville, Louisville, KY.

The low solubility of tyrosine (Tyr) in water restricts amounts of Tyrin amino acid (AA) solutions used in total parenteral nutrition (TPN). Tyrmay be an essential amino acid in the preterm infant and is a precursorof catecholamines important in brain function. Excess phenylalanine (Phe)in AA solutions in TPN is presumed to substitute for Tyr. However in 12of 13 infants on TPN we found low [Tyr] and high Phe/Tyr ratios in plasmaas compared to values in enterally-fed babies.

Catheters were implanted in the inferior vena cava in 3 groups of rats sand infused with: A) saline (chow-fed rats), B) TPN containing a standardAA solution, dnd C) TPN with y-L-glutamyl-L-tyrosine (Glu(Tyr))substituted for half the Phe in the AA solution. Blood was sampled at 0time and daily for 4 days. At 96 hours rats were sacrificed and brainsremoved. Deproteinized brain homogenates and plasma were analyzed by HPLC.Glu(Tyr) was not found in the brain and urinary loss was negligible.Concentrations at 96 hours (mean + SEM) were:

.

,.. -.-_--. ----_-._ .-.-_-.-

These results suggest that Glu(Tyr) can normalize Tyr and Phe/Tyrratios in plasma and may improve tyrosine nutrition in TPN.

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WHOLE BODY PROTEIN KINETICS IN POSTOPERATIVE PATIENTS RECEIVING TPNWITH BRANCHED CHAIN AMINO ACID (BCAA) ENRICHED SOLUTION. T.Tashiro,MD,Y.Mashima,MD, H.Yamamori,MD, M,Nishizawa,MD, Y.Takeda,MD, K.Takag~,MDand Y.Katsuura,MD Department of Surgery,Chiba Un 1 vers 1 ty, Ch l,b,a, JAPAN.

Alterations of whole body protein kinetics in surgically stressed

patients receiving BCAA enriched solution were studied.Twenty-two patients receiving gastric or colorectal operations were

divided into two groups, one received TPN with 21% BCAA solution (n=13).and the other received 30% BCAA (n=9). All patients were fed exclusivelyby TPN providing 2.0 g of amino acid and 35 kcal/kg/d pre- and

postoperatively. N balance (NB), rates of whole body proteinturnover(Q), synthesis(S), and breakdown(B) were measured pre-, 3 and10 poi using constant infusion of 15N glycine.

NB,mgN/kg/d, Q,S,and B,g.prot./kg/d, M+SEM, * p<0.05 vs. 211: BCAA

In conclusion, increased protein turnover was ovserved in 307 BCAAgroup throuout the study. N retention in 307 BCAA group was improvedon 3 pod with significant increase of whole body protein synthesis.

44

ARGININE CHANGES TO BE AN ESSENTIAL AMINO ACID IN THE RAT WITH MASSIVERESECTION OF THE SMALL INTESTINE. Y. Wakaboyashi, MD and E. Yamada, MDDepartments of Biochemistry and Anesthesiology, Kyoto Prefectural University ofMedicine. Kyoto, Japan.We present enzymologlcal and nutritional evidence which shows that the small intestine

is the indispensable tissue in the synthesis of arginine in rats. We assayed pyrroline-5-carboxylate synthase. the first enzyme of arginine synthesis from glutamate. in 32 rattissues, and found that 80% or more of the total activity was concentrated in theduodenum and jejunum. Thus, we investigated the effect of feeding arginine-deficientdiet(AD) to the rat with massive resection of the small intestine(SB rat). Experiments weredone for 6 SD rats(9 weeks old) in each group. Amino acids were determined by aBeckman 6300 amino acid analyzer. After 4 weeks, the SB rats lost weight 76 g in

average, whereas the control(transsected) rats gained 23 g. Arginine-replenished(AR)diet supported the SB and Control rats to gain 87 and 88 g, respectively, during theperiod. After the feeding. the concentration of arginine in the skeletal muscle was76.6H6.7. 230.8t67.5, 163.4t76.2, and 654.4±68.4 nmol/g for the SB+AD, SB+AR,Control+AD, and Control+AR, respectively. The plasma concentration was 52.518.2.103.5:t]9.0. 50.7t12.8, and 133.8±26.0 pM. respectively. The concentration of citrulline inthe muscle was 58.0+11.6. 70.6+21.5. 168.3i43.4, and 93.3t9.5 nmol/g and that in theplasma was 31.1t6.9, 45.3t9.4, 72.5±15.3, and 63.2±14.3 14M. respectively. When the ratswere intravenously administered ammonium acetate(0.4 mmol/100g BW). the plasmaammonium concentration at the end of the injection was 4494±825, 2398±822, and1 395*529 trg/dl for SB+AD, SB+AR, and Control+AR, respectively.The markedly reduced arginine level in the muscle, the weight loss, and the impaired

ammonium detoxification found in the SB+AD group clearly indicates that the smallintestine is the indispensable tissue in the in vivo synthesis of arginine in the rat.

45

J3JUNAI, PROTEIN ABSORPTION OF WHEY PROTEIN AND ITSHYDROLYSATE. G. Reicht, MD, W. P~tritsch, MD, A. Eherer, MD,K.-H. Smalle, MD, J.-M. Kahn, MD and G.J. Krejs, MD, Depart-ment of Medicine, Karl Franzens University, Graz, Austria andSandoz Nutrition, Berne, Switzerland... _ , -

This study was designed to compare protein absorption tromnatural untreated whey protein (WP) and from whey proteinpretreated by hydrolysis (H). Hydrolysis was accomplished byusing pepsin, Jflf;~~ntC~~o~~Iîri~e~~s1~nst;:~hni~u~~a~I~&subjects two different segmental perfusion techniques withmul?i- hurien tubes were used with a 30-cm test segment placedin the proximal jejunum. In study I an occluding balloon pro-~Ym’i.~e f~o~~~a~e1lj~~t~~~ieJr ~~~d~s~!ntgc~1,;1~~~ andpancreatic enzymes. In study II the infusion site was in thestomach. A 45-cm mixing segm ent between the infusion site andthe test segment was used to allow thorough mixing of the in-fused protein solutions with endogenous gastric and pancrea-tic enzymes. No occluding balloon was used in study II. Thetable gives values for total protein absorption, mea’sured asa-NH2-N in g/h/30 cm. (-) indicates absorption, (+) denotes&dquo;net luminal dain&dquo;.

absorption rates were constant during the two hours of theexperiment. The results of study show that there is no ab-sorption of WP in the proximal ]ejunum. ’IP was only absorbedwhen it was exposed to endogenous enzymes. In both studies Hshows a higher absorption rate than WP suggesting increasedabsorption of preh 1drolyzed protein fragments. With this mod-el the influence or gastric and pancreatic enzymes on proteinabsorption can be studied under physiologic conditions.

46

INACCURACIES IN TOTAL UWNARY NITROGEN ANALYSIS: FSJTENTmL ERRORS IN NITROGENBALANCE DUE TO SAMPLE PREPARATION K A 8o~m, MS. RA Helms. f’t)arm(), and MC Slam. PhDDepartment 01 ClII1ICal Pharmacy. UI1Iversáy of Tennessee, Uenøus. TN and Department of NutrdionP,esea,ch. McGaw. Inc . irvwe. CA

Nitrogen balance (NB) roo¡&oelig;ty used as a rreasure of protein utdaation Total ururary ndrogen (TUN) ISused as a measure of nitrogen excrehon and n calculating NB In clinical kibmalcmies. unne IS frequentlystOfed frozen prior to nitrogen analysis, which enhances precipitate formation Centrdugatron rs frequentlyused to remove solids and sedunents. Vortemng, an alternate preparation method, evenly dIStributesparticulate matter Thirty-three acddied urine samples were randomly obtained from a pre-exrsUng. trozertmventory of adult, postsurgical samples and were analyzed for TUN utilizing Pyro-<:hemtlumenesceoce. noSamples were wrarmed to room tempereture, vortexed fa approxunately ten seconds and split into twoahquots. One aliquot was centrifuged at 1,BW x g to( 15 mnutes while the other ws, vorlexed again for t 5seconds The supernatant of the Centrduged sample was transfered into a test tuoc The vortexed aliquotwas mmedaately sanipled from nud-sarrple Both samples were diluted wdh double dmtdled water andanalyzed on the same day, by the same technman. In all cases the vortexed samples resulted m greaternitrogen values [vortexed =t 1875~3 PPM (~). centrduged =7434z444 t PPM (mearuSD), p<O01,see figure) There was a mean dll1erence 01 38% between vortexed and centrduged samples.Centrdugation leads to an urklefestiniation of urinary nitrogen losses. Differences rangmg from 0 3 to 10 6g/L were observed in this study. However, there was high interpatent variability with respect to TUNconcentrations Possible sources lor ndrogenous losses In centntuged samples are precipitates 01proteins, cystine or uric acid, mucus, and cells It frozen storage IS unaVOIdable. samples should begradually wanned to 37~C to redissolve precvprtates such as uric acd, then vortexed pnor to samplurgrrud-tube for the most complete and accurate deterrrunatan of TUN This preparation method s applICable toanalysIS by Pyro-chemilumenesce or Kiektahl

Companson of TUN results for centrduged or voftexed unne samples

47

WHOLE BODY PROTEIN TURNOVER AND ENERGY BALANCE DURINC7 EtYPER-ALIMENTATION OF MALNOURISEiED PATIENTS WITH LIVER CIRRHOSIS:K. Nielsen, MD, J. Kondrup, MD, PhD, L. Marlinscn, H. Do~ing, K. Nicbcn, RD, E.S. Jensen,MS, 1’hD.’. Division of Hepatology A-2152, Rigshospitalet University Hospital, Copenhagen,Dcnmark.’Risø National Laboratory, Roskilde, Denmark.Aim: To examine whether liver cirrhosis decreases the utilization of protein and energy.Methods: Five malnourished patients with cirrhosis (Child grp. A) were fed increasing amounts

of food for a mean of 42 days. The intakes of nitrogen and enerbry (G,h) were registered. Theprotein intake increased from 0.92 to 1.65 g/(kg d). Protein turnover was measured before andafter hyperalimentation using primed continuous infusion of ’SN-glycine. Energy expenditure (E&dquo;,0was calculated (Eq. C),(1) or measured by the doubly labeled water method (Eq. M),(2). Theincrcase in lean body mass (LBM) was calculated J from the nitrogen retention (3). The gain in fatmass was calculated from the increase in triceps skin fold (4). The cnerb’Y cost (synthesis +deposition; in Eq. C), or the energy deposition (in Eq. M), equivalent to the increase in fat mass(E,M) and LBM (EUIM) was taken from ref. 3. A complete enerby balance was then calculated.

Results: The positive nitrogen balance increased from 022 to 0.80 g protein/(kg d) (p<0.01).The protein synthesis increased in all patients, from a mean of 2.3 to 2.7 g protein/(kg d), and thedegradation decreased from 2.1 to 1.9 g proiein/(kg d).Energy balance: (MJ/d, mcan:!:SEM), EuN= Energy unaccounted for.

The increase in nitrogen balance and the changes in protein synthesis and degradation are inaccordance with results from healthy subjects (5). The measured E. was 31% higher than thecalculated E~. The increased Ea was accouiitcd for by energy used for synthesis of tissue. Energyused for synthesis of tissue is similar to that of malnourished patients without liver disease (4).

Conclusion: Liver cirrhosis does not decrease the uliliwtion of protein and energy.1) Acheson KJ, et al. 1980, 2) Prentice A~1, et al. 1~85, 3) Forbes GB. 1987, 4) Barac-Nicto M, ctal. 1979, (5) )ccvananJaro M el al. 1986

48AM)NO AC1D LOSS DURING CONTINUOUS IIEMODIAPILTRATION WITiiAGGRESSIVE NUTRIENT AL161ENTATION IN SEPSIS. D.C. Fr~nk,~.F,,Id, MS,M. Badllino, MD, H.N. Reynolds, MD, C.E. Wilts, MD, J.11. Sie~e), MD. MarytandImtitute for EmerLencv Meclical Services Svstem. Baltimore. MD.

Continuous hèmodiatiltration (CHD) is a form of dialysis which rèmOVes solutes and fluidcontinuously in mute rènal failure, eliminating the need for protein/volume restrictions. Aminoacids (AA) are cl~red during CIID. AA loss into CIID efllucnt (dialysdtè vulumc (DV) +ultratiltrale volume (UV)) has not been mcasulèd during aggressive par&dquo;nkral AA feeding.

Plasma AA (PAA) and 12-hr CHD effluent AA concentrations were mwsurrJ 97 times in10 septic multiple organ failure (MOF) patients. Data were compared to 55 plasmalurine AApairs from 6 septic MOF control (CON) patients wilh normal renal function. Analysis waspafurm&dquo;d with ion-exchange liquid chromatography after dèprotcinizallon with sulfosalicylicacid. Twenty-six diflÚènt AA were mèàsuled, including the 15 AA found in TPN. AAintakc (maan :LSD) was 87± I8 (CliO) vs. 8~i i 21 gll2 hr (CON). Total AA loss was 7.27+2.35 (CIID) vs. 3.4+2.9 g/12 hr (CON) (p<.0001). Loss of the 15 TPN AA was 5.2 ±1.6(CliO) vs. 2.5+2.2 g/12 hr (CON) (p< .00(1) which was equivalent tu 6.2+2.5% (CIID) vs.2.8.:t2.2 % (CON) nf intakè (p<.0001). 1’ùlal AA loss was bcst prèJi&dquo;kJ by the, regrèssionèquation: -4.6+UV(.36)+OV(.26)+sum PAA(1.7) (R==.67, F,,~=57.8, 1’< .00(1). Eftluent

(E) alone is an acceptable predictor: 1.23+E(.29) (R’=,485, FI.~,=86. p<.0001) (UV, DVand E in LJ12 hr, sum PAA = nimol/L). AA intake pourly prwicted AA loss (R2=.002,p < .2). Brrausu AA loss is directly propnrtional tu E, a static gm or R~ AA luss should noth&dquo; assumed in CIID. Range of 9c loss of TI’N AA in the simple was 2..t7-13.~-t N. The

rc- rssiun @Litiition however will predict AA luss over a wide range of E. AA losses withCI ID are significantly greater than CON but may not be clinically signllicant except uhrn AAluss is in the high range StXonddfY to high E wlumr and AA inIal&dquo; is luw.

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49

ABNORMAL AMMONIA AND AMINO ACID METABOLISM DOES NOT EFFECT GROWTH INTHE FEMALE PORTACAVAL SHUNTED (PCS) RAT. K.Kaminsky-Russ, BS, H.

Conjeevaram, MD, KD Mullen, MD, S.Matuszak, BS Case Western Reserve

University, Cleveland, Ohio.The PCS rat has been used to study the consequences of portal systemicshunting for many years. The model exhibits altered amino acid andammonia metabolism with hyperammonemia and decreased branched chain/aromatic amino acid ratios (BCAA/AAA). These alterations may affect

body protein metabolism which in turn may influence the growth ratein these animals. In preliminary studies in this model we noted a

difference in growth between male and female PCS rats. We decided

to further investigate the growth patterns along with food intake,serum ammonia and amino acid metabolism in male and female shuntedrats. Methods: 30 male and 30 female Sprague Dawley rats of equal weightwere divided into 2 groups-PCS and Sham operated controls and studiedfor 4 weeks. Daily food intake and body weights were recorded. At

sacrifice blood was assayed for 24 individual amino acids and ammonia.Results: xtSEM or x only. *p <.01 vs. SHAM.

Conclusion: Despite similar food intake and individual amino acidprofile, NH3 elevation and reduced BCAA/AAA ratio, male but not femalePCS rats exhibited a decreased growth pattern. The mechanism(s) under-lying this gender difference in growth can be further evaluated.

50

URINARY UREA NITROGEN PLUS AMMONIA APPROXIMATES TOTALURINARY NITROGEN IN PATIENTS RECEIVING NUTRITION SUPPORT.J. Burge, RD., PhD., T. McKnight, MS., J. Mirtallo, RPh.,MS., A. Vargo, RD., P. Choban, MD., L. Flancbaum, MD. TheOhio State University, Columbus, OH.

-

Historically nitrogen (N2) balance has been estimated byusing urinary urea nitrogen (UUN) multiplied by a factor of1.25 to account for non ureaN2.(14UN2)in the urine. Recently,the reliability of UUN as an estimate of N2 losses has beenquestioned and the use of total urinary nitrogen (TUN) hasbeen proposed as a more accurate measure of urinary N2losses. However, analysis of TUN is not readily availablein many hospital laboratories. Since ammonia (NH3) is themajor fluctuating component of urinary NUN2, and measure-ment of urinary NH3 is available in most hospitals, this

study was undertaken to determine whether urinary NH3 plusUUN provided a clinically useful approximation of TUN. 24hr urine samples acidified with boric acid duringcollection from 10 patients receiving total parenteralnutrition (TPN) were analyzed for UUN, NH3 and TUN. The UUNvalues ranged from 4.9 to 23.1 gms/24 hr. The meandifference (MD) between TUN and UUN was +1.01 gms/24 hr,(range -0.65 to +2.87). The MD between TUN and (UUNxl.25)was -2.29 gms/24 hr, (range -0.27 to -3.23). The MD betweenTUN and UUN + NH3 was -0.18 gms/24 hr (range -1.47 to+0.01). These data suggest that UUN + NH3 is a reliableestimate cf TUN in patients receiving TPN.

51

PLASMA AMINO ACIDS AND PEPTIDURIA DURING INTRAVENOUS INFUSION OF A SHORT-CHAIN OVALBUMIN HYDROLYSATE OR ITS’ EQUIVALENT AMINO ACID MIXTURE INMAN. G. Grimblc PhD, P. Aimer BSc, P. Morris, B. Weryk BSc’,S. Collins LRSC, A Raimondo MD.D. Silk MD. Central MiJJlesea H.,;pit.1, London Xc ‘Phe University, Dmtdee. UK.

L-Amino Acids are the accepted form of nil rogen for TPN, but current interest in synthdic dipepiideshas highlighteJ the IIdvlUIUlges of short-chain protein hydrolysates (ie. AA profile, solubility and lowosmolality). This study investigllt&dquo;&dquo; the iv. utilisation of a partial enzymic hyJrolyaal of ovalbumin(996 AA, 75% di- & tripvptiJr,s, 1656 tetra- & p~:ntnpeptiJes) in man.On two measion!i, 7 fasted subjects were infu&dquo;w witlv two isocaloric, isonitrogenous TPN-solulions

for 5-6h. Solutions supplieJ Energy: 2000kcal/24h (35% ~ lipid) and Nitrugen: 12.BgN/24h m thehydroly&dquo;¡¡h: or its’ equivalent AA liCid mixture. Plasma AA’s were rnrauurecl in blood snmples at 0, 60,120, 180, 240, 360’. Baseline and 7h urine collutiuns were analysed for pc:phJes (capillaryelr,~ trophoresis) anJ pyro8lutarnate (pyglu) by IIPLC. DiI&dquo;-erenees were IISSCSseJ by paired t-Test.

Concentrations of essential AA’s increased during infusion but no Jhlcrences in levels uf any AA atany time point, between infusions, reached .t..ti.he..1 significanco. Capillary electrophumsis allowed 3groups of peptides to be assigned in urine and liydroly~i~ samples (swrll bas,e-, neutrdl- and largemutral peplide.). Pepliduria, which occurr&dquo;&dquo; in all collection periods, was highest during hyJroly~utoinfusion (esp. large neutfuls), the pattern of mluxal and excreteJ peptides being Jtssiuulnr. pyGluexcretion (umole) during hydrolysate and AA infusions was 174±62 and 79 + 13 (p<O.OOI).

Renal handling of iv. pc:ptides is clearly &dquo;&dquo;’Iuence specifie and dilferen&oelig;s in pyglu excretion mayreflect both the form (free or peptiJe-bounJ) and amount infused. The lack of d,lfcrence. in plasmaAA’s between stuJteS, suggests good bioevailib~ltty of this hydroly,,¡¡le. As > 90 % of the hydrolysatecouipn~d pt~plides, these dAta suggest thallhe body 10&dquo;&dquo; thc capacity 1. hydroly&dquo;&dquo; s&dquo;&dquo;,1I pepriJ.am yuantities sufficient to meet dAily N-r&dquo;’luiremenb. Short-chnin protein hydrulysatrs, enrich&dquo;&dquo; in di-and tripeptides.lherdore show pronux m a wUl Ul1h&dquo;&dquo;&dquo;,,lowoMuolalily N-sourcc for pc:ripher..1 nutrition.

52 1

LEUCINE: A UNIQUE EFFECT ON THE RECOVERY OF MUSCLE FATIGUE INVITRO. T. Manner MD, H. Yamada MD, H. Nagashima MD, S. Wiese

MD, D.P. Katz PhD, J. Askanazi MD. Department of

Anesthesiology, Montefiore Medical Center, Bronx, NY.Previous studies have demonstrated that branched chain amino

acids, in particular leucine, can improve the recovery of

diaphragmatic muscle force after fatigue. This study evaluateda dose-response curve for leucine. After 30 min ofstabilization in Krebs-Ringer Buffer (KRB) , rat hei.. i diaphragmswere incubated for 2 h with either KRB (contrc’), or withleucine at 3, 5, or 8 times plasma concentrat:on (0.15 mmol/Iin rat). Fatigue was induced by tetanic stimulation for 10 minat 5 Hz with 50% duty cycle. The recovery of muscle force

(isometric tension measured by single and 10 to 100 Hz tetanicstimuli) was significantly improved with leucine at the doseof 5 times plasma concentration, whereas further increase inthe concentration did not potentiate the effect. At 10 minafter fatigue with 10 Hz stimulation, the tension differencecompared to control was different (1.7% vs 12%, p<.05) for 3vs 5 times plasma concentration. Similarly, for 60 liz therewas a significant difference between 3 vs 5 times (1.7% vs15.2%, p<.025) and 5 vs 8 times (15.2% vs -8.8%, p<.04) plasmaconcentration. These results suggest that leucine may have aspecific pharmacological action not dependent on its use as anenergy substrate.

53 Fats/OilsLYMPHOCYTE MEMBRANE FLUIDITY IS CORRELATED WITHBLASTOGENESIS IN RABBITS FED CHOLESTEROL-SUPPLEMENTED DIETS.M.D. Peck, MD, ScD, Z.M. Li, MD, B.C. Pressman, PhD. Departments of Surgery andPharmacology, University of Miami School of Medicine, Miami, Florida.

...,

ilotn the cnolesterol content ana the degree ot tatty acyl unsaturation can auet tne

organization of the lymphocyte cell membrane. In this study, changes in the physicalproperties of the membrane, also known as &dquo;membrane fluidity&dquo;, were related to theability of the lymphocyte to respond to stimulation.

Three New Zealand white rabbits weighing 2-4 kg were acclimated on naturallaboratory chow, and then were switched to diets supplemented with 4% peanut oil and1% cholesterol. The rabbits were continued on the cholesterol-supplemented diets for sixweeks, and blood was sampled after 0 (control), 24, 31 and 38 days.

The lipophilic probe, diphenylhexatriene (DPI~), was inserted into peripheral bloodlymphocyte cell membranes, and the rate of depolarization measured with a

spectrofluorimeter to give an estimate of membrane fluidity (Rs). Lymphocytes were alsostimulated with the lectin Con A, and the uptake of tritiated thymidine measured (SI).

xr.,.....,.r rr&dquo;.,.. ~~..m...e~..~ ~..__1............&dquo;&dquo;............t

[1)ata are presented as the mean :tSEM, and comparisons done with Student’s t-iest. JMembrane fluidity and the stimulation index of lymphoproliferation were decreased by

feeding diets supplemented with cholesterol. The correlation between lymphocytemembrane fluidity and the lymphoproliferaiive response was 0.738.

In this model, &dquo;stiffening&dquo; of the cell membranes was achieved by feeding a diet high incholesterol to rabbits. The results indicate that changes in the physical qualities of thelymphocyte cell membrane are related to changes in function. This is further evidence ofthe influence of dietary fat on immune function.

54

INTRAVENOUS LIPID EMULSION (LCT NOT NIC’F) IN TOTAL PARENTERALNUTRITION (TPN) INHIBITS T-CELL AND MACIIOPIJAGE FUNCTION. M. Hoki,MD, PhD, M. Fuku/.awa, MD, PhD, R. Nczu, MD, Y. Takagi, MD, PhD and A. Okada, MD, PhDDcp.u (mcnl 01 Pcd~aW c Surgcry, 0,A-,i University McJtcul School. Osaka, JAPAN.Although an importance 01 lat cmulsion in,rl3N has been ac:c:cptcJ for many years, it’!i real clfcc on

Immune l’unclion ~a sllll controvcrslal. In this study, two different types of f.1I emulsion (I.c. MCT

(C.:C&dquo;,=77.23) and LCT) were compared on Immunc function. Male SD rats, 250gr, were divided into 4groups. Gp N; normal chow control. Gp M ind Gp L; 50% of nonprotcm calorie (NPC) wcrc suppliedwith MCf and LCT, respectively, Gp G; NPC wa.s supplied with gluwsc alone. Aftcr tx~nitrogcnousand isc~1(inc’rPN (2-%kcallkg/day, NPGN=l65) lor 4 d.lYs. anImals wcrc sacrificed. Splemc lymphocylcssubpopu!alÎons wcrc Imestlgalcd by FACSTM (E3ccW n Dicl,mscm Cc).) laser 110wqlomeler and splcnocytcscultured with RPMI 1640 media and concanavalm A (ConA). Lymphocyle bl.tswgcncsts was measuredby’ll-tti)-midine uptake for cach group. Furthermore, phagcxytcrsts assay was performed by using spicnicma.;n~ph.rgcs and latex bead&dquo; (I.O!ciÐ.Ol!1m, SIGMA).

t. ~~....._..,.~ C’&dquo;I-..~,~~..I .....~ n.. m ~wmv r-.~ r.~ . wma n_. ~ iwmv t:~ ~-_ .m_c

S’tutieti< rurulysi~ by S’lmterrt-Newrnurr-Keufs, p<D.OI: ’(ts Gp N); $(vs Gp M); i’(sn Gp G).

These resull, suppOl1lhat LC7 emulsion in TPN uiJmcJ suppression ol T-ccll blato6cncsts andblocking of relÍculoendothelial system function compared to MCf emulsion in TPN.

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55

DIFFERENTIAL EFFECT OF MEDIUM- AND LONG-CHAIN TR1GLYCERIDES ONTUMOR GROWTH AND METASTASIS. D Bartlett, MD, S Charlaruf, PharmD, and MTorosian, MD, Department of Surgery, University of Pennsylvania, and the Department ofPharmacy Practice, Philadelphia College of Pharmacy and Science, Phila, PA.

Parenteral nutrients can significantly alter tumor growth and treat malnutrition associatedwith cancer cachexia. To determine the effect of specific parenteral nutrients on primarytumor growth and metastasis, 35 female Lewis rats with sc mammary tumor implants(MAC-33) underwent SVC cannulation and were randomized to receive 1 uf 4 parenteralnutrient regimens: (1) TPN + LCT, (2) TPN + 75% MCTI25’;~ LCT, (3) TPN +Glucose or (4) Electrolytes (Control). All regimens were isocaloric and isonitrogenousexcept for the Control Electrolyte solution. After 10 days of parenteral infusion, animalswere sacrificed to determine carcass weight, primary tumor volume and lung metastases.

+p<0.05 vs. Control by I-Way ANOVATPN significantly reduced carcass weight loss and accelerated primary tumor growth

compared to control electrolyte infusion. Differential effects of TPN were found on thedevelopment of lung metastases: TPN+LCT > TPN+Glucose > TPN + MCT/LCT.TPN with mixed MCT/LCT may be used in the future to selectively treat cancer cachexiaby preferentially repleting host tissues and inhibiting tumor metastasis.

56

EFFECT OF MEDIUM-CHAIN TRIGLYCERIDE(MCT) ON METABOLISM IN SEPTIC RATS.M.Hasebe,MD, H.Suzuki,MD, E.tdori,PhD, T.Higo,htD and K.Kobayashi,MDTrauma and Critical Care Center, Teikyo University, Tokyo, JAPAN.

Although hypermetabolism in sepsis is an important response to recoverfrom the insult, conventional energy sources can not be well oxidized.We examined the effects of MCT on metabolism in septic rats.Peritonitis was produced by cecal ligation in rats. They were operatedagain 12 hrs later for removal of the necrotic cecum, tracheostomy andvenous catheterization. After these procedures, they were mechanicallyventilated and administered one of the following soluL>Jns for further12 hrs; normal saline(S), glucose solution(D), a mixture of glucose andLCT(L), and a mixture of glucose and MCT(M). Each group except group-Sreceived 120 kcal/kg/day. The ratio of fat to glucose in group-L andgroup-fd was 6 to 4. During the latter 12 hrs, energy expenditure(EE)was measured by indirect calorimetry. The blood, liver and muscle were

then harvested for assay of various metabolic parameters.EE of each group increased gradually for initial 8hrs and then reachedto a plateau. Cumulative EE(kcal/kg/12hrs) during the study was main-tained significantly higher in both group-Me 66 .6;;4.7) and group-L(62.6t1.8) than in group-D(52.0t4.7) or group-S(46.3±5.7). Protein level(mg/mgDNA) in the skeletal muscle of group-M(1147.t96) was higher than thatof group-D(975t96) or group-L(970;;102). Serum concentrations of inter-

mediates of fat oxidation, such as triglyceride, FFA and ketone bodies,were all significantly lower in group-M as compared with group-L.Large amount of energy expenditure and protein sparing effect were ob-served in the septic rats administered MCT. It was concluded that MCT

may be a beneficial fuel substrate in septic patients.

57

ENTERAL FEEDING WITH STRUCTURED LIPIDS CONTAINING FISH OILPREVENTS HYPERTRIGLYCERIDEMIA AND FATTY LIVER OF SEPSIS.

S.Lanza-Jacoby, PhD.,H.Phetteplace, Ph.D..R.Tripp, M.D. and A.Tabares, BSDepartment of Surgery, Jefferson Medical College, Phila., PA.

Fish oils (FO) have been shown to reduce plasMa triglycerides (TG). In this

study we evaluated whether enteral feeding with a structured lipid emulsion(SLE)containing FO would prevent the hypertriglyceridemia and fatty infiltration ofthe liver that develops during sepsis. Male, Lewis rats (275-300g) were fedintragastrically for 5 days a nutritionally complete diet containing SLE or thesimilar diet with safflower oil (SO) emulsion in place of the SLE. On the 5th daysepsis was induced by injecting i.v. BXIO 7 live E.coli/100b.w; 24 hours later thecontrol SLE, septic SLE, control SO and septic SO rats were killed. Feeding theSLE and the SO reduced the plasma TG of the septic rats by 20°lo in comparisonto the control rats. The decrease in plasma TG was associated with over a 2 foldincrease in lipoprotein lipase activity in the soleus muscle of tl. ~eptic SLE rats(64.1+7.5u moles FFA/g) in comparison to the control SLE rats (23.8+4.6u molesFFA/g) and septic SO rats (31.5+2.6u moles FFA/g). Fatty liver did not occur inthe septic rats fed SLE(436+66m5/liver) when compared to the control SLE rats(578+87mg/liver). The content of the liver TG in the septic SLE rats alsodecreased by 62~’.. The reduction in liver TG appeared to be due to the higherrate of TG secretion from the livers of the septic SLE rats (O.132+0.l4u moles/ml perfusate/90 min) than the control SLE rats ().087,0.013 u moles/mlperfusate/90 min. Feeding SLE with FO prevents the hypertriglyceridemia andfatty infiltration of the liver associated with gram-negative sepsis.

58

IN VITRO UTILIZATION OF LONG-CHAIN VS MEDIUM CHAIN FATTY ACIDSIN SKELETAL MUSCLE OF TUMOR-BEARING RATS. T. Foley-Nelson, PhD, A.Stallion, MD, J.H. James, PhD, W.T. Chance, PhD, and J.E. Fischer, A1D. Depanment ofSurgery, University of Cincinnati, Cincinnati, OH.

Significant weight loss impairs recovery in the catabolic cancer patient. Current dataindicate that while body weight can be increased with enteral and parenteral nutrition, thiseffect is due primarily to increased total body fat and water. Indices ofprotein conservation(muscle protein content) are not positively impacted. A majority of nutritional formulasutilize long-chain triglycerides as a lipid source. There is, however, strong evidence thatmedium-chain triglycerides (MCT) are more rapidly and completely oxidized. The

following study determined if long- and medium-chain fatty acids were differentiallyutilized by skeletal muscle under normal and catabolic conditions.Four groups of six rats [(a) freely-feeding; (b) 96-hr food deprived; (c) tumor (methyl-

cholanthrene-induced sarcoma)-bearing; and (d) pair-fed non-tumor-bearing] were anes-thetized and two strips were dissected from each soleus and extensor digitorum longus(EDL) muscle. Muscle strips were pre-incubated for 30 min in Krebs-Ringer bicerbonatebuffer with 5 mM glucose and either 0.25 mM octanoic acid (medium chain-length) or0.25 mM palmitic acid (long chain-ICnbth). During the subsequent 2-hr incubation,muscles were treated identically except for the absence of glucose and the addition of 0.1 1¡.tCi/ml of either (1-14C]-palmitate or [1_14C]-octanoate. Utilization was estimated by theproduction of t4C02. Utilization of the medium-length octanoate was two- to three-foldgreater (p<0.05) than that of the longer palmitate for all groups, both in soleus and in EDL.These data indicate that medium-length fatty acids are preferenti...ly utilized by musclesunder catabolic conditions and thus may represent a preferred SOl.,ee of lipid calories innutritional support of the cancer patient.

59

ABSTRACTWITHDRAWN

60

LIPID EMULSIONS IMPAIR IN VITRO HACROPHAGE TNF PRODUCTION. W.D.

Vazquez, G. Arya, V.F. Garcia, Department of Pediatric Surgery,Children’s Hospital Medical Center, Cincinnati, Ohio

Intravenous lipid emulsions are an important component of parenteralnutrition. Despite its benefits, lipid emulsions have been associatedwith higher rates of bacteremia in neonates. Therefore we investigatedlipid emulsion’s effect on the inflammatory response by examining itseffect on in vitro macrophage Tumor Necrosis Factor (TNF) production oftwo distinct macrophage populations. Using endotoxin free PBS,peritoneal (PER) and alveolar (ALV) macrophages were isolated from maleSprague-Dawley rats (125-150 gms) with endotoxin-free PBS. Cell countswere adjusted to 2xlo6 cells/cc in RPMI with 2% FCS. 300 ul of thecells were incubated in a 24 well culture dish with media or media with

intralipid (1% final concentration) for 16 hrs. After washing eachwell 3 times, the cells were stimulated for 2 or 16 hrs with E.coli LPS(150 ul of 1 ug/cc). The supernatants were assayed for TNF using theWEHI 164:13 bioassay and TNF levels were expressed as pg/cc. Student’s

paired t-test was used for data analysis.

Simulated peritoneal and alveolar macrophage TNF production wasiower after 2 and 16 hr of LPS stimulation. TNF production appears tobe impaired in macrophages exposed to a 1% lipid emulsion for 16 hrs,which may help explain the increased rate of bacteremia in those

patients receiving lipid emulsions.

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61

EFf-KT OF INTRAVENOUS FI9I-9DYT3FA?I-OIL EalULSI~d CN cERM FATTY ACID COMPOSITIONIN TOTAL PARENTEML NUIRI’1’ION. X~!a&hima,MD,T.1hshiro,MD,H.Yama)nori,MD,H.Misawa,MD,M.Nishizawa,MD, K.Qkamoto’’,FHD, First Department of Surgery, Chits University, Schoolof Medicine, &dquo;Tsmmo Co.,JapamThere has been accumulated evidence to support the importance of including linolenate

derivatives(rr-3 essential fatty acids, especially C20:5n-3,EPA and C22:6--3,DHA) innutritional care for critically ill ¡:atients. ’Ihe ooly n-3 essential fatty acid whichis available in an a¡:p’6Ciable amount with intraverdus soybean fat emulsion (SFE) islinolenate. However, the conversion rates of linolenate to its hi&oelig;ctive derivatives,EPA or IHA, in humans are very low. We, therefore, remtly fahicated a new 107 intra-.venous fat emulsion (FOE which contains fish oil 1.57 and soybean oil 8.5%). The comtents of EPA and IIIA in F&OElig; are 200mg/dl and 200mg/dl respectively. To stlrly the ef-fects of ~E, the changes of serum fatty acid profiles in TFN patients Cl1 differentfat regimens were studied. In fat free TFN, sudden decr~ses in serum concentrationsof EPA and ilIA were observed. These concentratims of EPA and #N were at the levels of2 SD less than normal mean values (EPA 2.32:.Ü3%, and *A 6. 7;tO.L,%). These were otservedwithin one week after the commencement of TPN, ar~d continued to decrease gradually toaroizd 0.5% and 1.57 respectively after 30 days. TFN with SFE to supply 10% or 25% oftotal calories as fat(l, cases of each) failed to attain EPA om L’HA levels to normalrar~ges. Daily administration of FOE 250ml or 500ml ( 4 TFN cases of each) increased EPAand IHA levels toward normal levels within one week ard maintained these levels. Anypossible adverse effects of FOE were not observed in TFN patients who daily receivedFOE for up to 6 weeks. Also any linoleate deficiency irrlices were not o&oelig;ervoo. Theseresults indicate that FOE administration is a safe ard Wtent wc~y to supply n-3 fattyacid derivatives such as EPA ard I7HA as well as n-6 fatty acids in favorable talance oncritically ill TFN patients

62

EFFECT OP A DIET GNRICIIrD WITII M FATTY ACIDS ON PlATELET LIPIDS, PLATrLCTAGGREGATION AND TRANSFUSION R!!QUIRLMGNTS. M. Gol clrlich, PhD, RD, T. Baumcr, DTR,J. Khoury. MS, M. Jenkins, RN, MDA, G.D. Wardcn, MD, Shrincrs Burns 1~&dquo;tiI~~c, Cincinnali, Oll I

L.On~l(lcr;&dquo;llJlc nucrcst cztsts w-3 tany ictus ~~-snn~ anct ~xtmatca ncann ucnctns m Icrms oi

immunity and inflammatiun following burns. However, tu-3rA supplementation has been reported to prolonghleeding time, rcducc platelet cotints and deercase platelct adhesiveness in other paticii( populations. Aprospcetive sludy randomized 45 burn palicnts to 3 separatc isonitrogenous tubc feeding regimens (% ofKcal): Group 1-high fat (39%); Group 2-moderate fa1 (29%); Group 3-low fat (12%), fish oil fortified(6gm/L). Quantitative and qualitativc fat intale was measurctl daily; platelet aggregation testing, scrumcholesterol and (riglycefidcs, and fatty acid eompooition of individual phospholipids in the platelets wereconducted weekly during the first 4 weeks postburn.

- .... -- - - - --

Thc 3 groups were not statistically different in age, % burn, % third, number of surgical procedures,plolélet counts, or total blood transfused per % burn, % third or meler squared I3SA. Variablcs innucncingamount of blood transfused werr lo burn (p<0.0001), % third (p< 0.000 I smoke inhalation (p<0.03),infection (p<0.003) and number of surgical procedures (p<0.00t11) but not the diet fed. There was no cffeetof diet on the fatty acid compwitinn of individual ph&oelig;;pholipid~ in thc platelets. The magnitude of plateletaggregation to epinephrine, colligen and iriclii(ionic acid dccrcaxd significantly in burn patients coinpiredto controls. Abnormalities to eollagen (weeks I & 4) and cpincphrinc (wccl,s 1 & 3) became morepronounced when subjects were inge~ting the low fat, ~r-3FA diet (p<0.04). Mean serum (riglyccride levelsfor Ihox patients receiving Fish oil werc significantly less than measurement, in Groups I and 2 by week 4(1’<0.006). There was no cffcet of the Fish oil dict on xrvm eholestcrol. The data indicate that

supplementing an enterat diet with 6 gm/L of fish oil docs not potentiatc hemorrhage. The lack ofincorporation of w-3FA in platelet phospholipids and crratic effects. on plotelet function may bc exploincd bythe dilulional effects of platelet free agents such a’ blood and intravenous fluids.

63

EFFECT OF KETONE BODIES ON CONTRACTILITY OF THE RAT DIAPHRAGMIN VITRO. T. Manner MD, PhD, D.P. Katz, PhD, A. Rudick, MS, J. IAskanazi, MD. Department of Anesthesiology, Montefiore MedicalCenter, Bronx, NY.Ketone bodies, the key metabolites from medium chaintriglycerides, are a potentially useful fuel for tissues withan increased energy demand. The effects of 8-hydroxy butyrate(6-HB) on in vitro diaphragm function were assessed in the ratmodel. Thirty-six diaphragms were divided into hemidiaphragms(HD) ; one HD served as control and the other was randomlyassigned to 1, 4, 6, or 8 mmol B-HB following a 30 minequilibration in Kreb’s buffer. The figure illustrates time vstension force (mean; t from baseline; *=p<0.05, **=p<0.01),elicited by 20 Hz direct stimulation, before (control) and

following a 10 min inductionof fatigue by tetanic stimuli.Measurements of tension forceat 10, 60, and 100 Hz showedsimilar results. The data showsan improvement of contractilityand recovery, suggesting abeneficial role for B-HB as anenergy source for the fatigueddiaphragm.

64

TIlE EFFECT OF KETOSIS ON LIVER REGENERATION OF THE AGED RAT. Y. Nishiguchi, MD,M. Nagayama, MD, M. Okuno, MD, M. Sowa. MD and’R. H. Birkhahn, PhD. First Department ofSurgery, Osaka City Medical School, Osaka, Japan and Medical College of Ohio, Dept. of Surgery,Toledo, Ohio.

.... -

wouna healing decreases witn age, and liver regenemuon alter pamat ncpatectomy as a model ot woundhealing also slows down with age. Monoacetoacetin, the monoglyceride of acetoacctate, enhanced liverregeneration in young rats, and it was of interest to determine its effect on livers of older rats. Tcn-monthold male rats were divided into two groups: I ( N=55 ) received 18 g Glucose / day and If (N=55 ) 13 g gMonoacetoacetin + 5 g Glucose I day. Both diets contained 4 96 amino acids, vitamins, minerals and wereinfused at 72 ml / day. Rat.a were anesthetized with ketamine and acepromazine, received a jugular vcincatheter and 70 % partial hepatectomy. Rats were infused with 0.9 96 saline at 2 mllhr for 6 hr aftcrpartial hepatectomy and then dietary infusion was begun. Five rals from each group wcre sacrificed at 6-hr intervals beginning 12 hr and ending at 72 hr after partial hepatectomy. Each rat was given an ipinjection of 13HIthymidine two hours before termination. At termination livers were resected, fixed informalin, sectioned, and mounted on glass slidcs.’1’hymidine in DNA was exposed by autoradiography.Slides were stained with hematoxylin and cosin for counting the labeled and mitotic cells.. Approximately1000 hcpatocytcs were counted in each of three 7.one ( periportal, intcrmcdian, and peficentral 7.Ones ) ofliver lobulcs to determine the °h~ labeled (silver stained ) and mitotic cells. Values at each time point werelabcled cells ( 96 ) *

= p < 0.05 vs Glucose,:-. 1 I- 1 17 I 1 G to O 7A in 1~ Al A. CA !J~ 79

These data showed that feeding monoacetoacetin with glucose initiated liver regeneration earlier andstimulated more cells into DNA synthesis and mitosis than did feeding glucose alone in the aged rat.

65

EARLY POSTOPERATIVE ADMINISTRATION OF ENTERAL OR PARENTERALNUTRIENTS IMPROVES WOUND HEALING. G.P. Zaloga, MD,L. Bortenschlager, MD, K. Black, LAT, Dept. of Anesthesia,Bowman Gray School of Medicine, Winston-Salem, NC.

Previous studies have shown an improvement in woundhealing when nutrients were administered shortly followinginjury compared with delayed nutrient administration. This

study was designed to evaluate the effect of early enteralversus parenteral nutrient administration upon body weightchanges and wound strength following abdominal surgery.

Sprague-Dawley rats (n=24; 350-450 g) were divided into3 groups. All animals received a duodenal and jugularcatheter for administration of isocaloric/isonitrogenousdiets. A 4 cm abdominal incision was made and closed in auniform manner. Animals received either TPN immediatelyafter surgery (TPN), a peptide-enteral diet immediatelyafter surgery (ENT), or the peptide diet 72 hours aftersurgery (LATE). Wound strength was measured on day 5 usinga balloon bursting pressure technique. *p<0.05.I , --

~ar~y aam~n~5~ra~~on or nu~r~en~5 improvea postoperativeabdominal wound healing. There was no difference in healingbetween TPN and ENT, however, weight loss was greater withTPN than ENT.

66

INCIDENCE OF CIIOLESTASIS IN INFANTS RECEIVING PARENTERAL NUTRITION: COMPARISON3F AMINOSYNpF AND TROPliAMINE. K. Gura,RPh, M.L. Forchielli, MD, A. Cartin,4S’ RD, C. Lo, MO, PhD, R.Sandler, MD Departments of Pharmacy andGastroenterotogy and Nutrition, children’s Hospital, Boston, MA ard Rush-Presbyterian-St. L~k!’s Medical center, Chicago, IL.

The incidence of PN associated cholestasis (PNAC) in premature infantscan be as high as 50%. Anecdotal reports have noted a decrease in theincidence of PNAC since using the taurine supptcmented pediatric amino acidpreparations, in particular TropliAmine (McGaw). To evaluate the possibleassociation of cholestasis with PN, we reviewed the records of all patientstess than 1 year of age who received PN for greater than 14 days during 1990(n=67). The patient population was divided into the 2 time periods, before andafter August 1990, in which Children’s Hospital switched trom Aminosyn PF(Abbott) to TrophAmin(~. Charts were reviewed for potentially confourding PNACvariables such as nunbcr r of septic episodes, nmber and type of surgical pro-cedures, and duration of PN prior to initiation of feedings. Of the 67patients < 1 year of age on PN for > 14 days, 30 received Aminosyn PFexclusively, 27 received TrophAmine alone, while the remaining 10 receivedboth formulations. overall, 26 (39%) developed cholestasis, as defined by adirect bilirubin _>2 mg/dl. Cholestasis without confourxfing conditions wasfound in 18 patients (27X), white the remaining 8 (12%) may have developedcholestasis secondary to other factors in conjunction with PN.

Conclusion: the use of TrophAmine in this population of severely ill infantsdid not appear to have a significant impact on the prevention of PH associatedcholestasis.

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67

SERUM IMMUNOREACTIVE ERYTIlROPOIE1lN CORRELATES WITH GROWTHRATE AND HEMOGLOBIN LEVEL DURING INFANCY. J.A. Widness, MD & P.J.

Kling, MD Department of Pediatrics, University of Iowa, Iowa City, IAErythropoietin (Ep) is thought to be the major growth factor controlling erythropoiesis

throughout development. Although Ep production is stimulated by tissue hypoxemia, it isalso influenced by nutritional status. Because there are no data on the relationship ofserum Ep, hemoglobin (Hb), and growth in normal formula-fed term infants during thepenod ot physiologic anemia, wemeasured serum Ep (by RIA) andHb levels monthly in 25 normalinfants during the first 7 mos oflife. In addition, since rate ofgrowth has been correlated withEp levels in neonatal animals, weexamined the relationship of Epwith growth rate. We observedthat Ep correlated indirectly withhemoglobin (r = -0.49. p<0.0001, Figure left), and directly with growth rate of weight (r = 0.48, p < 0.0001,Figure right) and of length (r = 0.35, p < 0.0001, not shown). Rates of growth werejudged normal based on concordance with standardized growth charts. When Ep wasexamined as the dependent variable using multiple regression, both Hb and rate of weightgain were significantly associated with Ep (multiple R = 0.55, p <0.0001). Thus inaddition to the anticipated negative feedback effect of oxygen delivery on Ep production,we speculate that rapid growth and/or nutritional factors may also influence serum Eplevels in normal formula-fed infants during the first months of life.

68

EFFECT OF DEXTROSE (D) AND GLUCOSE POLYMERS (GP) ON METABOLICACIDOSIS IN SHORT BOWEL SYNDROME (SBS). JM Saavedra MD, SV McAdoo MS,RD. Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD.

Absorption of the products of fermentation of malabsorbed carbohydrate (CHO) can lead tometabolic acidosis in SBS. We assessed the effect on metabolic acidosis of substituting a morereadily absorbed CHO (D) for GP in the enteral feedings of these patients. Five infants withSBS ages 2 - 10 mo (mean 6.2 mo) were given a protein hydrolysate formula with glucosepolymers (Pregestimil-Mead Johnson Nut.) or a very low carbohydrate formula (MJ3232A-Mead Johnson Nut.) to which D was added to deliver the same amount of calories and CHO.The patients were assessed for one week on each formula. Three patients received parenteralalimentation, 2 oral antibiotics and 1 citrate throughout the evaluation. Stool volume, pH,reducing sugars, weight gain and serum C02 (3 times weekly) were measured.

In all cases the use of D allowed further advancement of enteral feedings. Conclusion: Thesubstitution of D for GP improves the acidosis in SBS. We speculate this is due to enhancedabsorption and decreased luminal fermentation of carbohydrate.

69 Short Chain Fatty Acids/FiberTHE EFFECT OF FIBRE-FREE ENTERAL DIETS AND THE ADDITION OF SOYPOLYSACCHARIDE ON HUMAN BOWEL FUNCTION AND SHORT CHAIN FATTY ACID

(SCFA) PRODUCTION. Ana H. Raimundo, M.D., S. Kapadia, M.D., Donna L. Terry, M.S.,R.D., P. Fieldcn, BSc., and D.B.A. Silk, M.D. Department of Gastroenterology, CentralMiddlesex Hospital, London. U.K.

...

The role ot Ubre supplementation ot cnteral diets m optlmlsmg bowel lunctlon is still

unclarilied. The aim of this study was two fold: 1- to compare intcstinal function (stoolweight, bowel frequency and whole gut transit) during thc administration of a fibre-freeenteral dict (FFD) and a supplemented with Soy polysaccharide entcrat diet (SPD). 2- tocharacterize the fermentability of the soy polysaccharide (SP) fibre source used in thesediets. Seven healthy volunteers (mean age 25), were ramdomly assigned to two treatment

periods (7d) of FFD (Enereal Plus, Wyeth, 21/24h), or the same diet supplemented with20g/L of SP (SPD, enercal + fibre, Wyeth).Whole gut transit time was measured using asingle dose marker technique. A previously described in-vitro 24h fermentation techniquewas used to simulate the anaerobic metabolism of human colonic bacterial nor in vivo.

25g of the volunteers fresh stool was mixed with a 500ml nutrient medium and 15g of soypolysacharide. The SCFA were measured by Gas liquid chromatography. Results: 1- (Mean+SEM, n=7), Thcre was no significant difference in the stool weights (g/24h) betweenFFD 9t.4+16.6, v.s. SPD 72.3+8.5 ; no significant difference in bowel frequency (times/day)during FFD (0.78+0.1) v.s. SPD(0.71+0.1) or in thc whole gut transit time (h) during FFD(67.9+9.1) v.s. SPD (71.7+6.4). 2- There was a significant increase in the production ofSCFA mmol/L after 24h human feacal incubation with SP (meam+SEM, n=6). Acetic acid(p< 0.003) at Oh 9.75+9.5 v.s 24h 57.3+9.5; Propionic acid p<0.001 (1.45+0.1 v.s 25.7+3.7)and N-butyric acid (p<0.002)(1.21+0.2 v.s4.7+1). In conclusion the addition of SP to cnleraldiets has no effect on bowel funetion, but it yields short chain fatty acid production.This might be beneficial as a means of providing fuels for the colonic epithelium and as

a stimulus for the absorption of sodium and watcr across the colonic mucosa.

70

EFFECT OF SOLUBLE AND INSOLUBLE DIETARY FIBER ON SHORT CHAIN FATTY ACIDCONCENTRATIONS IN COLONIC FLUID. J.L. Slavin, PhD, RD and J.W. Lampe,PhD, RD Department of Food Science and Nutrition, University ofMinnesota, St. Paul, MN.

since Short chatn tatty aclas (SLr~A) are tnougnt to be importantfactors in the positive effects of dietary fiber in enteral feeding, wecompared the in vivo production of SCFA while 6 normal male subjectsconsumed enteral diets (Resource8, Sandoz) supplemented daily with 21 gmaltodextrin (0 g fiber), 21 g enzymatically modified guar gum(Sunfiber~, 100% soluble fiber), and 21 g soy polysaccharide (Fibrigo,20% soluble fiber). Subjects consumed all diets in random order. Thelast week on each 18 day experimental diet and on their self-selecteddiet, subjects swallowed dialysis bags for collection of colonic fluid.Dialysis bags were retrieved from freshly collected fecal samples, bagcontents eluted, and SCFA analyzed by gas chromatography. No signifi-cant differences in total SCFA, acetate and propionate concentrations(umol/ml) were seen among diets. However, butyrate concentrations(mean ± SE) were higher on the self-selected diet (24.6 + 16.5) than 0

g fiber (7.5 1.6), modified guar (11.1 ± 5.3) and soy fiber diets(9.1 ± 2.7), p - 0.02. The molar percentage of propionate (% of totalSCFA) was lowest and t butyrate was highest on the self-selected dietcompared to the enteral diets, p - 0.001 and p - 0.0007, respectively.In addition, % acetate with 0 g fiber tended to be higher than thefiber supplemented and self-selected diets, and was lower with self-

selected intake than enteral feeding, p - 0.05. Thus, differences in

SCFA production were seen between self-selected diet and enteral dietsrather than with type of fiber c~nsumed with an enteral diet.

71THE EFFECT OF SOLUBLE FIBER AND FRUCTOSE IN ENTERAL FORMULAON GLUCOSE TOLERANCE IN DIABETIC PATIENTS. A. Golay, MD andH. Schneider, PhD 1. University Hospital of Geneva, Geneva,Switzerland, 1SANDOZ Nutrition, Bern, SwitzerlandThe aim of this study was to evaluate the effect of a spe-cial enteral formula (Nutrodrip Diabetic R)(EN+F) containingfructose (30g/L)and guar gum (21g/L) on postprandial plasmaglucose (PG) and insulin(IRF) excursions in 6 non-insulin

dependent (Type II) diabetics in comparison to a standard,fiber-free enteral diet (EN) containing sucrose (30g/L). Thepatients received isocaloric amounts (900 kcal) of enteralformula in the morning after alO h fast, following a rando-mized double-blind, cross-over design. Incremental areas un-der glucose (IAPG) and insulin (IAIRI) curve over 4 h were

calculated geometrically. The results are in mean ± SEM .

1. The formula with fructose and guar gum resulted in marke-dly reduced peak values of PG and IRI. 2. Significant reduc-tions in IAPG and IAIRI were observed following ingestion ofthe fructose and guar gum containing formula. In conclusion,the positive effect of fru rose and guar gum incorporationinto an enteral formula offers an interesting potential forenteral feedinq of patients with impaired qlucose tolerance.

72

FIBER SUPPLEMENTATION INCREASES NONPROPAGATED DUODENAL MOTILITY. H.C.Lin, M.D. and Y.G. Gu, M.D., Nutrition Center. Cedars-Sinai Medical Center, Department of Medicine,UCLA School of Medicine, Los Angeles, CA.Since the prevalence of liquid stools on enteral feeding is reduced by the addition of water soluble fibers

to enteral feeding (JPEN 1989;13:117), fiber supplemented formulas have been widely used to preventdiarrhea. Although nutrients decrease the motility of the small intestine (DDS 1989; 34:1873), Gbcrsincrease intestinal motility (Gastro 1981;80:701). Since intestinal transit depends on the pattern ofmotility (slower transit with more nonpropagated (NP) activities), we hypothesized that fiber slowsintestinal transit to prevent diarrhea by increasing the NP motility. We tested this hypothcsis in 3 dogsequipped with duodenal fistulas and 3 duodenal serosal electrodes by comparing duodenal motility whileOsmolite (low residue, Ross) or equicaloric levity (fiber supplemented, Ross) was perfused into theduodenum at 50 or 100 mlft1r. During thc last 30 min of a 90 min perfusion, duodenal myoclcctricalsignals were digitized and stored on a computer for analysis. Since myoelectrical spikc burst (SB)activities correlate with contractions, a program was used to count the number of SB that propagatcd(migrated across 2 or 3 clectrodes) vs. those that were NP (round by only one electrode).

11, number of electrodes migrated across by $pike bursts, values were meanstSEI) At 100mi/hr, the summed motility of Jevity was greater than Osmolite (p<.05, t-tcSl); specifically,nonpropagated SB activity was greater with Jcvity than Osmolitc (p<.05, t-test) and 2) The summedmotility of Jevity at 100 mvhr was greater than at 50 ml/hr (p<.05, t-test); specifically, nonpropagatedSB activity was greater (IX.OI. He-5t). In summary, fiber supplementation increased the overall duodenalmotor activity in a dose-dependent fashion by specifically inereasing the nonpropagaled motility.(Supported by Ross Laboratories Medical Nuvition Services)

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DOES COLONIC ACIDIFICATION STIMULATE EPITIiELIAL PROLIFERA-TION IN THE ABSENCE OF SHORT-CHAIN FATTY ACIDS? W.ScheppachMD, P.Bartram, MD, F.Richter, F1D, G.Dusel, E.Schulz, H.Kasper, MD. Dept. of Medicine, University of Wurzburg, FRG

In this study the hypothesis was tested that acidifica-tion of the medium may increase proliferation of coloniccrypts in vitro and that this effect may be unrelated tothe presence of butyrate (a luminal trophic factor).

Biopsies taken from the normal cecal mucosa of 24

patients were incubated wit!¡ HC1, butyric acid, Na-butyrateand NaCl (control). Proliferating cells were labeledimmunohistochemically with bromodeoxyuridine. The number oflabeled (1) and unlabeled (u) cells in 20 longitudinallysectioned crypts of every experiment was evaluated and a

labeling index (LI=1/1+u) calculated.

(mean + SEM, *p < 0.02 vs control, Wilcoxon test)The presence of luminal trophic factors (short-chain

fatty acids) and not acidification per se seems to affectcell turnover in the colon. This is important in long-termparenteral nutrition where mucosal atrophy may occur.

74

SPECIES DIFFERENCES IN TPN-INDUCED INTESTINAL VILLUS ATROPHY. H.S.Sitren,Ph.D,M.Bryant,n.D.andL.M.EI1is,M.D. Food Science andHuman Nutrition Dept., University of Florida, Gainesville, FL.

Although it is widely held that TPN leads to pronounced atrophy ofintestinal villi, evidence to support this contention is found primarilyin rats, which show mucosal atrophy within 3 days of TPN. However, inadult humans, 3 weeks of TPN results in diminished brush border enzymeactivities but no changes in mucosal protein nor villus height, cryptdepth, or mucosal thickness(Gastroenterology 90:373, 1986). We studiedintestinal adaptation in a group of adult mice maintained on TPN for 8days. Another group was pair-fed the formula per os(PO) while a third

group was pair-fed a balanced solid diet. Mucosal index, a measure ofthe proportion of mature and immature cells in the mucosa, was

calculated from the villus length and crypt depth. Results showed thatbrush border disaccharidase activities in the TPN group were markedly yreduced throuqhout the 4ut comnired with controls.

*(N); No significant differences among group means at P<0.05 by ANOVA.Villus morphology assessed by light microscopy appeared normal in

TPN fed mice. We conclude that the response of the mouse smallintestines to TPN is similar to the human and unlike the reported villusatrophy in parenterally fed rats.

7~ Glutamine

GLUTAMINE SUPPLEMENTATION DECREASES SYSTGhIIC N4ETIIOTIIEXATECLEARANCE. SL Chariand, PharmD, DL Bartlett, MD, and N411 Torosian, MDDepartment of Surgery, University of Pwnsylvania and the Department of PharmacyPractice, Philadelphia College of Pharmacy and Science, Philadelphia, PA.

Glutamine-supplemented diets have been shown to decrease the enterocolitis associatedwith methotrexate (MTX). To investigate the mechanism of this phenomenon, h1TXpharmacokinetics were studied in female Lewis rats randomized to receive one of twoisocaloric, isonitrogenous diets (4.20 Kcal/g; 25.0%a protein): (a) glycine-supplementeddiet (Control; 3.1 ‘9o glycine) or (h) glutamine-supplemented diet (GLN; 1.03’o glutamine)ad lib for 35 days. All rats received hITX (10 mg/kg IV) and serial blood samples werecollected at 0, 5, 15, 30 minutes and 1, 2, 3 hours to determine serum MTXconcentrations by HPLC. MTX pharmacokinetics ivolume of distribution (Vd), ~I,..cance(CL) and half-life (T,nJ~ were determined and analyzed by nonlinear least squaresregression. No significant difference in weight gain or dietary intake was observedbetween groups.

GLN supplementation signiticantly decreased systemic MTX clearance (l25’fo) which~r~>lungs host tissue exposure and would, in theory, increase gastrointestinal toxicity.Thus, GLN-supplementation must reduce MTX induced enterocolitis by localgastrointestinal protection and not by systemic changes in h9TX pharmicukinetics.

76

PHARMACY PRODUCTION OF A GLUTAMINE-CONTRINING TPN MIXTUREFOR CLINICAL INVESTIGATION. G.Hardy PhD, G.Grimble PhD and

B.McElroy B.Pharm. Oxford Nutrition OX43UH,Central MiddlesexHospital and Royal Shrewsbury Hospital SY38BR U.K.

We have shown that a sterile 2.5% Glutamine (Gln) solution

prepared aseptically in the hospital pharmacy can be storedfor 30 days at 4t with loss of Gln less than 0.05%/day.Conversion to Pyroglutamate(Py-Glu) is 0.02%/day and Ammonia(NH3) formation is less than 0.4mmol/l.No Glutamic acid(Glu)is formed (Hardy et al 1991).

Compounding this Gln solution with Elamin(15%aminoacids)Elo-lipid(20%fat emulsion)ElotraceB(LEOPOLD PHARMA) Glucose 50%MVC9,3(LYPHON’D) in 31 multilaminate bags we have formulateda complete Tr:. regimen containing: 15gN (93g aminoacids inc.lBgGln) 200OKc~1(50:50 glucose:fat)Na8O K80 CaS Mg7 P30 mmoltrace elements and vitamins in 2500mi for storage at 4t for30 days. By standard enzymatic analysis: Gln decreased by2.8%(0.1%/day) NH3 increased from 0.106 to 0.253mmol/l(total

NH3108mg/bag within tolerable levels for mammalian tissues).Glu and pH(6.30) were unchanged. The homogeneous mixtureshowed no visible cracking,90%particles remained< 2um (93%for Gln-free control).We conclude that this TPN admixture exhibits little loss of

Gln during refrigerated storage over 30 days and the productis pharmaceutically acceptable for clinical investigations.

Hardy G et al (1991) Clinical Nutrition Spec.Supp.2:36

77

GLUTAMINE-ENRICHED ENTERAI. DIET(GEED) INCREASES MUSCLE PROTEINSYNTHESIS AND SPARES HOST WEIGHT IN TUMOR BEARING RATS B. Ng, BS, R.F.Wolf, MD, N.A. Vydelingum, PhD, M.F. Brennan, MD Surgical Metabolism Laboratory,Memorial Sloan-Kettering Cancer Center, New York, NY.

Since cancer cachexia leads to muscle wasting, efforts have been made to preserve host proteinmass. We examined the ability of GEED to preserve host tissue and protein synthesis. Fischerrats were inoculated with MCA-induced sarcoma on day 0. Animals were maintained on regularrat chow until day 17 and 24. Animals were randomizect into 2 groups: GLN [glutamine (GLN)-enriched diet-5.9gm GLN/500cc Criticare 1~N] and CTL (an isonitrogenous, isocalorie glycine-enfiched diet-6.Ogm GLY/500cc Critic&dquo;’&dquo; HN). Each group was fed for 7 days. On day 25 and32, after an 18 hr fast, animals recev I an intraperitoneal flooding dose of’H-phenylalanine(phe)(50pCil50gmBW). 15 min after injection, animals were sacrificed, gastrocnemius muscle(m)was resected and frozen in liquid N2 and subsequently analyzed for free intracellular and protein-bound phe specific activities by HPLC and fractional protein synthetic rates (FSR, Y6/Jay) werecalculated. [GLN]..(p.mole/gm) was detemùncd enzymatically. All data expressed as mean + SEM,comparisons by t-test. (carcass wt=body wt-lumor wt(gm), significance as p<0.05-. vs CTL)

No differences were observed in total food intake among groups.Animals receiving GEED had a significantly increased FSR&dquo;&dquo; carcass weight, and [GLN1..

compared to controls, with no difference in tumor burden. GLN as a nutritional supplement maybe prove useful in cancer cachexia.

78

EFFlic7r OF CLU’fAMINE SUPPLEMENTATION ON LYt~’HOi:Y’fE FUNCTION IN SEPTICItATS. S.Yoshida MD S.Hikida MD, Y.Tanaka 14D, A.Yanase MD, ii-M izote MD.and 1’.Kaepawa HD. st Dept of Surgery, Kurume Univ., Fukuoka, Japan,The previous report showed that Klutamine administration attenuatedthe mucosal atrophy. The objecfive of our study is to determine whetherglutamine supplementation is effective on lymphocyte flU1clÍon in septicrats, because glutaruine is an important energy fuel for not onlyenterocyte but also lymphocyte.18 male SD rats were randomized into 3 groups:l control rats with oralintake ad lib.(C), 2) sepsis with standard T N(S and 3)sepsis with

glutaroine TPN(G). Glutamine was supplemented as alanyl-glutamine.Glutamine TPN was isocaloric (250kcal/kg/day) and isonitrogenous(1.5gN/kgfday) with std. TPN. 25X of total nitrgen was gi en asglutamine. On day 1, 13 rats were catheterized and either S or Gm fusion was begun. On day 3,sepsis was induced by cecal ligation andpuncture. 6 hours after the mduction of sepsis, resection of cecum andresuscitation was done. On day 5 48 hours after the resuscitation, theanimals were sacrificed and the blood was collected. Serum lymphocytecount (1.£) was measured. Lymphocytes were stimulated byphytohemakglutinin (PIIA), and JH-thilaidine uptake was co~mted todctenuine nlÍtogenic actIvity. Data are mean(SEH). Differentsuperscripts indicate significant difference from one another. Stat. byANOVA.:

We concluded that glulamine stivplew~~iitation was beneficial to theI)roliferIaLion of lymphocytes a~ter the resuscitation of bitcueriogenicperitonitis rats.

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31S

79

EFFECT OF GLUTAMINE ON UREA RECYCLING IN SEPTIC RATS.S Yoshida MD, MD Schluter MS, MJ Leskiw BA, S Lanza-Jacoby PhDand TP Stein PhD. Dept. of Surgery, University of Medicine andDentistry of NJ-School of Osteopathic Medicine, Camden, NJ andThos. Jefferson Univ., Phila. PA..

Systemic sepsis induces an increase in urea production (UP) andurealysis by bacteria to ammonia (urea recycling, UR). The objectivesof this experiment were: (1) to quantitate the effect of systemicsepsis on UR and (2) determine whether adding glutamine (GLN) tothe TPN infusate could attenuate the increased UR. Rats (210-260 g,n =21 ) were cannulated for TPN, given a std balanced TPNformulation for 4 d and then randomized into 4 groups. control (C),control + GLN (C+G), control septic (S) and septic + GLN (S+G).Sepsis was induced by iv injection of 10» E. Coli. 20 hr. later aprimed (1.75 mg/rat) continuous infusion (0.5 mg/h for 4 h) of 15N2urea was given. After 4 h the rats were sacrificed and UP and URcalculated from the ~SN2 and ~SN~°N enrichments of the blood urea.Results are mean (SEM), units are mg/kg/h. Statistics by ANOVA.

Conclusions: (1 ) Systemic sepsis increased UP and UR. (2)Addition of GLN to the TPN infusate attenuates the increased UP andUR.

so Trace Minerals and Vitamins

Is silicon deficiency Involved in the pathogenesis of metabolie hone disease of children rueiving parenteral nutrition? A.

Moukarzel, MD, PhD; M. Son& MD;1. Haddad, MD; A. Buchman, MD; If. Baron, MD¡ J. Varga.. MD; L Reyen, RN; W. Gu...Pham~D; M. Ament, MD. UCLA Medical Center, Ins Angeles, CA 9001A.

Silicon, a grace nutrient performs an important roll: I., connective tissue, npec’lally In bone and cartilage. Silkon’s primaq=,In bone and cartilage appears to be on the formation of the organk matrix. Bone and cartilage abnormalities areassociated with reduction In matrix component&dquo;, resulting In the establishment of requirement for Silicon In cotiagen andglytosaminoglyean formatiom Additional support for Silicon’s metabolic role in connective tissue Is provided by the findingthat Silicon is a major ion of osleogenit cells, especially high In the metabolically mlive slate of Ihe cell (Se Tot Envir 88;72:95-106). Children receiving long term TPN suffer from metabolic bone disease of unknown etiology charatterieed by generalizedosteopenis.

The present study was designed to determine serum Silicon in healthy controls and children reteiving TPN and to correlaleSilicone to Ihe degree of osleopenia. Serum Silkon was measured by atomk absorption speclropholometry (PERKINS-ELMERmod. #2380) with IIGA 400 graphite fumme. Trabecular gone niinemi content was measured by computeriaed tomographyat L&dquo; tl, 11, and L4 and compared to age and xx matched controls. 25 subjects aged 10.1 ± 5.2 ( x ± SO) years receiviagTPN for 9.0.t 4.8 years were studied.

The mean serum Silkon kvel (207 + 68 ng/ml, range 106-376) was slatisikally lower then that of control (547 ± 390 ng/nll,range 55. p<O.OOI). The Silicon conlamination In individual glucose-aminoacid solutions ranged trom 0.3510 1.08 mg/i,and in fat emulsion was lA2 ± .21 mg/L The subjects were retefring daily 0.6 to 1.2 nig parenleral Silicon. Silicon ronteniof adult U.S. diets is 19 10 50 mg/day (Food Add Cant In IS subjects, the Irabecular bone mineral content was77.5 ± 17.3% (range 46-10196) of normal conlrols. The mineral content torrelaled significantly with the duration of the TPN(r=-O.54, p< 0.05), and poorly with the Silicon kvel (r=+0..a5, p<0.10). In concluslon,lhese observations suggesl ihai Inchildren receiving TPN, the lower Silicon krel might have certain metabolic consequences, among them contribulion to thedecrease of bone mineral content.

81

Boron deficiency Is not an etiological factor In the osteopenia of parenteral nutrition bone disease Inchildren.

A. Moukarzel, MD, PhD; M. Song, MD; J. Vargas, hlD; A. Buchman, MD; H. Baron, MD; W. Guss,PharmD; L. Reyen, RN, M. Ament, MD. UCLA Medical Center, Los Angeles, CA 90024.In two human studies, Boron deprivation was detrimental to calcium metabolism and bone formation,Recently, the influence of Boron supplementation of three mg per day on the prevention of calcium lossand bone demineralization in postmenopausal women has been shown (FASER J> 1987;1:394-7).Children receiving long term TPN suffer from metabolic bone disease with osteopenia of unknownetiology Boron deficiency has been hypothesized as one potential etiology.The present study was designed to determine serum boron In healthy control and children receivingparenteral nutrition (TPN) and to correlate the levels to the degree of osteopenla. Serum Boron wasmeasured by atomic absorption spectrophotometry (PERKIN-ELMER md.#2380) with HGA 400graphite furnace. Trabecular bone mineral content was measured by computerized tomography at L&dquo;1.&dquo; L3, and L, and compared to age and sex matched controls. 28 subjects aged 10.2 + 53 (x + SD)years receiving TPN for 9.1 + 4.9 years were studied.Contrary to our primary hypothesis, the mean serum Boron (11.6 + 1.5 mcmol/ml; range 5.9 - 18.1)was significantly higher than that from controls (B.8 ± 2.8 mcmol;range 7.2 - 12.3, p< 0.02) andcorrelated with the duration of TPN (r= +0.44, p<0.05). A significant contamination of Boron Inindividual glucose (1-3.1 mcinol/1) and in fat emulsion (1-1.2 mcmol/1) was observed. The subjectswere receiving daily 0.9-2 mcmol (9.4 to 30 mg) parenteral Boron. In 15 subjects, the trabecular bonemineral content was 773 + 173°fa (range 46-101%) of normal controls. The mineral content correlatedwith the duration of the TPN (r=-o.54,p<0.05) but not with serum boron (r=-0.12, NS). We eonciudethat there Is enough Boron contamination In TPN solutions to maintain serum Boron at or abovenormal levels. Boron deficiency is not characteristic of the osteopenia seen In children on long termparenteral nutrition.

82SELENIUM RE-DISTRIBUTION DURING SELENIUM SUPPLEbIEIYI’ED TOTAL PAREN-TERAL NUTRITION IN RATS. K Sando, M. Hoki, R. Nezu&dquo; Y. Takagi and A. Okada.Department of pediatric Surgery and the First Department of Surgery*, Osaka Univerrity, MedicalSchool Osaka, JapanThe purpose of this study was to evaluate the effect of selenium (Se) supplemented total parcnteral

nutrition (TPN) (Se(+)TPN) on the Se re-distribution. Weanling rats were divided into two groupsas follows; Group N. normal diet and then received Se(+)TPN, group D: deficient diet and

Se(+)TPN. Se concentration in plasma, and Se contents in heart, liver, kidney and gastrocnemiusmuscle were measured. Glutathione peroxidase (GPx) activities in plasma and organs were assayed.

,. - ~ .... -1~, - - ....

-

,-. ~ - -,

compared*: to N-pre, o: to D-pre, &dquo;: between 1 and 2W, (P < 0.05)Plasma Se level and muscle Se content were signifcantly lower than N-Pre, even though Se was

supplemented. Muscle GPx activity showed no significant change, compared to N-Pre. These resultssuggest that Se re-distribution may occur during Se(+)TPN, and that plasma is a carrier of Se andmuscle stroes Se in the less bioavailablc form.

83

ZINC STATUS DURING VITAMIN C-INDUCED NORMALIZATION OF ERYTHROCYTESORBITOL IN INSULIN-DEPENDENT DIABETES MELLITUS. P.A. Mearkle, BS andJ.J. Cunningham, PhD Department of Nutrition, University ofMassachusetts, Amherst, MA.

Erythrocyte sorbitol (e-sorb) is elevated in insulin-dependentdiabetes mellitus (IDDM) and is reported to respond to vitamin C(vitC) supplementation. We investigated zinc (Zn) status during thisnormalization since: (1) Zn participates in sorbitol metabolism and(2) hyperZnuria is a hallmark of IDDM. Habitual dietary vitC intakesfrom food records and plasma concentrations of vitC were normal in 10IDDM vs 11 nondiabetics, but e-sorb was 21+4 nmol/g Hb in IDOM vs 12+2(p<0.01). VitC at 100 or 600 mg/d for 30 days and 60 days reducede-sorb in all IDDM subjects with variable changes in nondiabetics. As

groups, e-sorb was lowered to normal in IDDM and unchanged innondiabetics. HyperZnuria was present in IDDM as expected (895±180ug/d vs 500+91) and, enexpectedly, fell at day 30 to 620+100 ug/d inconjunction with a lowered plasma Zn (0.83 mg/1 vs 0.96 at baseline).VitC also lowered plasma Zn in nondiabetics (0.80 mg/1 vs 0.92)without altering urinary Zn. At 60 days of vitC, hyperZnuria in IDDMreturned (840±91 ug/d) as pl-Zn recovered somewhat (0.89 mg/1). P1-Znin nondiabetics remained low at 0.83 mg/1. Erythrocyte Zn was lowerin IDDM, perhaps reflecting Zn stores, and remained constant in bothgroups throughout. These data suggest that the vitC mediatedreduction of e-sorb in IDDM does not involve improved Zn status.Further, vitC supplements appear to lower pl-Zn in all subjects.

84

VITAMIN K LEVELS AND EPOXIDE/VITAMIN K RATIOS IN PEDIATRIC BONE MARROWTRANSPLANT PATIENTS RECEIVING PARENTERAL NUTRITION. A. Carlin, MS, RI); K.Davidson, MS; J. Sadowski, PhD; M. O’llrien, BS; It. Weinstein, NID; C. Lo, MD, PhD Divisionor Ga~trocnterolottY and Nutrition and Ilematolgy and Oncology, Children’s n..spltal, Harvardhledical Sclmol and Tufts-USDA Ifuman Nutrition Research Center, Boston, I11A.Bone marrow transplant recipients are at increased risk for developing vitamin K deficiency as aresult of inadequate oral intake, gut slerili/.ation, and usc of parenteral nutrition (PN). VitaminK is not routinely added to PN formulalions for children x 12 years of age. Additionally, certainantibiotics may act as antagonists in the conversion of vitamin K epoxide to vitamin Kt. Weserially measured vitamin K, (phyllnquinone) and vitamin K epoxide by 11PLC, as well as

prothrombin time (PT), before transpiint and weekly thereafter until the paticnts were weanedoff PN 3 - 8 weeks later. Fourtccn p,iticnts were studicd; 8 < 12 ycars of agc who receivedvitamin K in their PN and 6 patients z 12 years who received PN without vitamin K. All paticntsreceived lipids (1-iposyn) providing 0.5 - 1.7 gm fat/kg. Vitamin K, levels in all patients wereHithin or abovc thc normal adult range of 0.3 - 1.3 nmol/L. Two patients x 12 years developedprolonged PTs although vitamin K bels normal. Several patients, 5/8 receiving PN with r,~itaminK and 5/6 receiving PN without vitamin K, exhibited epoxide/vitamin K ratios > O.OG indicatingpossible pharmacologic antagonism. 9/10 of thcsc patients received multiple tntibiotics. In

patients < 12 years, abnormal cpoxiJcJwamin K ratios were generally seen pre-transplant andcorrected once PN with vtamin K BBas begun. Thc amount of ,itdmin K pro,iJcd by the lipidcmulsion (2fi.5 mcg/100 mls) may be sufficient to sustain normdl serum lc%cis in 1’:llients withoutany other source of vitamin K. Thc effect of vitamin K antagonists on the clotting cascade mayonl) he apparent after an extcndcd period of drug therapy.

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85 Metabolism

DYNAMIC CHANGE OF THE RETICULOENDOTHELIAL SYSTEM FUNCTION FOLLOWINGSURGICAL STRESS. H.Ishida,MD. T.TsuJinaka,MD, Y.Kldo.MD.Y.Hayashida.MD, A.Ogawa,MD, S.IiJima,MD. T.Homma.MD, M.Sakaue,MD.K.Kan,MD, C.Ebtsut.MD and T.Mori,MD Department of Surgery II.Osaka University Medical School. Osaka, Japan

An in vivo functional test for the reticuloendotbelial system(RES) was established using chondrottin sulfate iron colloid (CSFe)In rabbits (JBBM in press). Employing this method, a normal rangeof the RES function In healthy volunteers (n=12) and a dynamicchange of the RES function in surgical Patients underwent distalgastrectomy (n=5) was examined.

The clearance rate of CSFe from the blood was calculated bymeasuring serum Fe concentrations after releasing Iron from CSFe atcertain intervals after injection. The maximum phagocytic velocity(Vmax) and the CSFe concentration producing 1/2 Vmax (Kp) wascalculated on the Lineweaver-Burk plot after graded injections ofrelatively low doses of CSFe.

Following data (mean ±SD) were obtained: In healthy volunteers;Vmax = 0.0310 ± 0.0052 mg/kg/min and Kp = 0.575 i 0.205 mg/kg. Insurgical patients; Vmax = 0.0387 t 0.0083 and Kp = 0.483 + 0.156before operation: Vmax = 0.0420 ± 0.0043 and Kp 0.540~0.320 onpostoperative day (POD) I: Vmax = 0.0630 _+ 0.0053 and Kp = 0.850 ±0.199 on POD 3: Vmax = 0.0593 i 0.0106 and Kp = 0.753 0.287 onPOD 7.

Upon the surgical stress, Vmax significantly Increased and Kpshowed a tendency to Increase. These results Indicate that thetotal capacity of the RES is augmented but the functionalphagocytic efficiency of the RES may be deteriorated followingabdominal surgery. The CSFe clearance test is useful to monitorthe dynamic change of the RES function under various conditions.

86

SIGNIFICANCE OF OBESITY ON NUTRITIONAL, IMMUNOLOGICAL, HORMONAL ANDCLINICAL OUTCOME PARAMETERS IN BURNS. NI.NI. Goitschlicti, I’hD. RD, T. Baunier, DTR,G.D. Warden, MD, Sluiners Bum Institute, Cinciimati, Oluo

Obesity (OB) is rarely regarded as a significant risk factor following bum injury. potential addniveeffect of OB on select nutritional (REE, nitrogen balance, creatinine liciglit index, glucose, transferrin,prcalbumin), immunological (IgG, C3, a2-macroglobulin, al-acid glycoprotein and al-antilrypsin), hormonal(insulin, glucagon) and clinical outcome paranwiers (infection, death, days requiring insulin, antibiotics orventilatory therapy) was evaluated in 28 patients with a R body surface area burn of 45.5% (range 14-78.5%)and x age of 26.5 (range 11-52 years). Fourteen patients characterized as OB by the following criteria:a) il8 years of age with weight tIO01h NCHS percenllle or b) > 18 years of age and ~120% ideal bodyweight; were randomly matched for age, % burn, % fullthielrncss burn and smol:e inhalation to 14 nonob-(NO) patients: a) 518 years of age with weiglit ~50th NCHS percentile or b) > 18 years of age and 90-100%ideal body weight.

Transterrin values for the OB group remained suppressed throughout the rimi 4 weeks postburn while thetransferrin levels of the NO group normalized by week 4, a2-Macroglobulin values for OB were markedlylower and OB glucagon levels were greater throughout the study period compared to the NO group. The OBgroup required significanlly more days on mechanical ventilatory support (p=0.05). Incidence of clinical

sepsis was greater with OB (p=0.01). Exogenous insulin supplementation (OB A days = ls.5t5.6, NO srdays = 6.612.3) and antibiotic therapy (OB ~ days = 6.9t2.3, NO sr days = 3.611.6) were required overtwice as many days with OB although these trends did not reach statistical significance. Tlie~ datademonstrate numerous deleterious effects associated with obesity and suggest the OB burn patient is prone togreater morbidity.

87

GROWTH IIORMONE (HGH) IMPROVES LIVER, SKELETAL MUSCLE, AND WHOLE BODYPROTEIN ECONOMY IN BURNED RATS. K.Takagi.MD, T.Tashiro,MD,Y.Mashima,MD, H.Yamamori,MD, M.Nishizawa,MD, Y.Katsuura,MD Departmentof Surgery, Chiba University, Chiba, JAPAN.

The efects of exogenous HGH on the protein metabolism of liver,skeletal muscle, and whole body were studied.

Thirty-one SD rats were subjected to 20% deep second degree scaldburns. HGH of 200 mU/d was injected to 16 rats for 3 days pre- andpostburn day (&dquo;HGH&dquo; group). Saline was injected to 15 rats(&dquo;Control&dquo;). All rats were fed exclusively by TPN providing 6.2g of amino acid and 200 kcal/kg/d. Whole body protein synthesis(S),and breakdown(B) were measured on the second postburn day usingconstant infusion of 15N glycine. N balance(NB), urinary excretionof 3-Methylhistidine(3-MH), and N content of liver and gastrocunemiusmuscle were also determined.

In conclusion, exogenous HGH significantly improved N retentionof muscle, liver. and whole body. Increased synthesis rate ofskeletal muscle and visceral protein were suggested.

88

CIRCULATING CYROKINES AS MEDIATORS OF THE HYPERMETABOLIC RESPONSE TOINJURY. G.J. Jurkovich, MD, R. Heiskel, RN, G.B. Hahnel, MS, S. Washburn, MS, RD, R.V.Maier, MD. Harborview Med. Ctr., Dept. of S~gery, University of Washington, Seattle, WA

The hypermetabolic (HM) response to injury can not be explained solcly on the basis ofelevated stress hormones. Cytokine administration mimics much of the HM response, andcytokine levels are known to be elevated after shock. We asked, do elevated serum cytokinelevels occur after injury, and do they by themselves account for the HM response?

Nineteen adult severe trauma victims (ISS>25) were consented and enrolled, kept NPOand TPN-withheld for 4 days, and assessed on post-injury day 1 and 3 for the following: serumIL-la, IL-6, dr TNF levels; total 24-hr urinary nitrogen excretion (TUN, gN/24hrs); indirectcalorimetry (IC-MEE); and APACHE II scoring. Nutrition was provided to achieve >_8096 of

predicted needs by day 6, and similar determinations made at day 6, 9, and q. week.ISS (meaA+SEM) was 38L+3. Day I and 3 APACHE II score was 17+1 and 12I2. Day 1 and 3

TUN was 17.9~+1.4 and 13S+lS. Day 1 IL~, IL-la, and TNF levels were elevated in 5996, 5096,and 2296 of patients. Similar results were obtained on day 3. Multiple linear regressionanalysis failed to demonstrate any correlation between pre-feeding cytokine levels and ISS,APACHE II, TUN or IC-MEE. Only day 3 IL-6 levels correlated with IC-MEE (R2=.49, p=.02)Mean total-stay cytokine levels in survivors (n=17) differed from non-survivors (n=2) as shown:

We conclude that serum levels of 1L-6,1L-la, and TNF are detectable and elevated in someseverely injured patients, and may be markedly elevated in patients suffering lethal injury.Early post-injury serum cytokine levels do not correlate with nitrogen loss, energy expenditure,or injury and illness scoring systems.

89

NUTRITIONAL PARAMETERS OBSERVED DURING 28-DAY INFUSIOhJ OF rh-TNF-a.T.C. Hardin, J.M. Koeller, J.G. Kuhn, T.D. Brown, J.B. Craig, G.D. Roodman, D.D. VonHoff. Departments of Medicine and Pharmacology, University of Texas Health ScienceCenter, San Antonio, TX.

Seven adult males with a variety of tumor types were enrolled in an antineoplasticPhase-I evaluation of 28-day continuous IV infusion of rh-TNF-a. Five pts. received10 mcg/m2/d and 2 pts received 25 mcg/m2/d. Indirect calorimetry measurements,serum TNF concentrations and laboratory analysis of common nutritional markerswere performed at baseline, day 14, day 28, and 2 weeks after completion of infusionto assess any changes which could be attributed to TNF infusion.

The table below summarizes our observations (mean t std. dev.):

A poor correlation between serum TNF concentration and REE was observed. Therewere no statistically significant differences (ANOVA) in any parameter during thestudy period. Also, there were no differences between parameters when stratified bydose administered, although the number of patients is very small. While others have

reported significant metabolic changes associated with acute administration of TNF inhumans and animals, our experience does not support a hypermetabolic state inpatients receiving low-dose, long-term (28 d) continuous IV infusion of TNF, a statewhich is consistent with most neoplastic conditions.

90

INTERLEUKIN-1 INCREASED THE LUNG TAURINE UPTAKE. Y. Hashiguchi, MD, H. Saito,MD, Y. Fukush’una, MD, K. Taniwaka, MD, H. Naka, MD, T. Muto, MD Department of Surgery,University of Tokyo, Japan

’

tnterteukin-1(tL-l) and tumor necrosis factor(TNF) play an important role in the pathogenesis ofthe adult respiratory distress syndrome. We demonstrated that IL-1 increased the lung uptakeof glutamine and alanine when administrated exogenously as alanylglutamine(Ala-Gln). On theother hand, taurine, which is abundant in free amino acid pools, is reported to protect the lungagainst oxidant injury. Our recent data indicated that infusion of IL-1 or TNF increased thearterial level and liver release of taurine. Thus, alanine, glutamine, and taurine may protect thelung in stressful condition. In this study, we investigated the effects of intravenous infusion ofIL-1 and AJa-Gin on the net rates of taurine exchange across the lung and other organs.Thirteen dogs underwent laparotomy and placement of catheters. BkSOd It, of the liver, gut,and hindlimb was measured with an ultrasonic flow probe. Cardiac output t. determined bythermodilution method. Studies were performed on POD 1 in an awake con_,lion. Alter a basalmeasurement, IL-1 was administrated to IL-t group as a continuous intravenous infusion(5pg/kg/h) for three hours. Ala-Gin infusion (6~Ukglmin) was started at 1 h after the onset ofIL-1 infusion and continued for 1 h simultaneously with IL-1. Control group received Ala-Ginwithout IL-1. Uptake ot taurine by the organs(negative denotes release) were as follows:

- ..- - 7- -.. -- -- . -.- -.- -,- -.-- -,--

Mean in pmol/kcymin (Arterial Level: Ilmolll). ’p<0.05 vs. Oh, &dquo; vs. 1h. # vs. controlWe conclude that It_-i markedly increases the lung taurine uptake. Taurine seems to play animportant role for protecting the lung in stressful condition. Taurine infusion may be effective inpreventing lung injury.

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91 Nutrition Assessment

BIOELECTRICAL IMPEDANCE ANALYSIS (NOT BODY WEIGHT): A GUIDE TOPOSTOPERATIVE FLUID MANAGEMENT IN COMPLEX CATABOLIC PATIENTSTA Byme, RD,MS,CNSD. MR Scheltinga, MD, C GaLzen, FRCS(E), DJ Sugarbaker, MD,DW Wilmore, MD, Department of Surgery, Harvard Medical School, BosLon, Ma.Postoperative fluid and nutritional management are commonly guided by changes in body weight

(~WT); however, AWT inaccurately represent changes in total body water (ATB W) when accompanied byrapid changes in body fat (BF) and protein (BP). Bioelectrical impedance analysis (BlA), a wtuiique whichdetermines TBW, defines the proportion of AWT which is due to water, allowing the combined change inBF and BP to be determined by subtraction. To investigate the relationship between AWT and ATBW, 7lung transplant recipients were followed until discharge. Daily BIA measurements were used to determineATBW which was compared to AWT. In two of the patients, cumulative caloric and nitrogen balance wereuscd to determine the change in BF and BP; subtracting these from AWT gave an alternative measure ofATBW, which was compared to that obtained by BIA. Data represent rates of change over 7 days for thepatients, who were generally stable, during the fast two weeks following operation (mean-tSEM).

*p=0.018 vs AWt by Wilcoxon signed-ruik testDetermination of the combined change in BF and BP by balance verified the det.....lination of TBW by

BIA and explain all but 0.16 kg of AWT. Over the one week period a mean loss of 1.5 kg was observed,as opposed to a mean TBW gain of ttearly 1 liter. Over a three week period, the tettdency for fluid retentionbecame even more pronounced with a maximum water gain of 5.liO.57 liters and a corresponding weightgain of 2.5iO.69 kg. The data suggest that OWT inaccurately reflects changes in hydration in complexcatabolic patients and masks the loss of body tissue. Serial BIA offers a more scnsitive index of measuringthe fluctuations in TBW and, when used in combination with AWT, can more accurately define the severityof a catabolic response and assess the approprialcness of nutritional intervention.

92

MUSCLE FUNCTION AND BIOENERGETICS IN MALNOURISHED RATS. Kearns P, VaughnC, Struck R, Armstrong R, Jeejeebhoy K; Dept of Medicine, Univ of Toronto, Toronto,Ontario, CANADA.Muscle function tests and bioenergetics vary according to nutritional intake. Change in 3~ Pmagnetic spectra and relaxation rate (RR) during stimulation was studied in rats fed restricteddiets. Randomly assigned Wistar rats received ad libitum intake (C), water only for a 2-day -fast(2DF), or 5 g of chow for 1 week (H). Refed (R) were H animals who ingested unlimited chowfor a week before testing.The gastrocnemius-soleus-EDL muscle (complex) contracted under direct sciatic stimulation.Isometric force recordings provided RR and force. The complex lay constrained in a solenoidcoil within a 2.0 Tesla magnet’s bore. Ten NMR spectra sequenced 6 seconds apart wereaccumulated before and following each contraction. Freeze clamped biopsies from lowerextremities were analyzed for ATP. Analysis of variance compared qroup values.

ATP levels were well preserved. There were no differences between groups in theunstimulated condition. The decrease in RR, force of contraction/g muscle, PUPCr andPCr/ATP ratios was more prominent in 2DF compared to C. H, and R. Differences in Pi/PCrand PCr/ATP were significant 12 seconds after tetany but not at 59 seconds (p= .0656) intorecovery. This suggests that rate of recovery is slowed in 2DF compared :.:. other groups.

93

ROUTINE LABORATORY PREPARATION OF 24-HOUR URINE SAMPLES FOR NITROGENDETERMINATIONS INDUCES FALSE LOW TOTAL URINARY NITROGEN (TUN) LEVELS.F. N. Konstantinides, MS, C.N. Moga, V.K. Hennan. BA, W.E. Warren, BS, and F. B. Cerra, MDSurgical & Clinical Nutrition Research FaciGty, SL Paul-Ramsey Medical CenLer/Ramsey Clinic andDept. of Surgery, Univ. of MN, St. Paul & Minneapolis, MNTUNs measured by pyrochemiluminescenceT1< (PCL) remain the gold standard when determining

urinary nitrogen losses for nitrogen balance studies in support of clinical nutrition. Acidification(HCL) and cold collections, although unnecessary, remain the common practice procedures used at thebedside when collecting 24-hour urines for TUN determination. Likewise, in order to removeparticulate matter which could interfere with and/or clog analytical machinery, representative urinealiquots are centrifuged prior to measurement. Previous studies have demonstrated that nitrogencontaining materials (i.e. uric acid) may precipitate and thus lead to incomplete nitrogen analysis. Inorder to examine this potential problem, 24-hour urines, acidified and frozen, were ana1y¿cd for TUN byPCL following centrifugation (CENT), again following vigorous vortexing (YORT), and again afterheating (H1’) to 50° C and adjusting pH to 7-8. The following results. expressed in gram~/collection asthe differettce between matched samples. were obvair~ed:

..M- ..-

It is evident trom this data that U1e common pracuce ot centrifugation ot act&dquo;&dquo; ana cold cOltecteaurines significantly decreases nitrogen levels as much as 13.20 glcollecúon. Although heating and pHadjusunents should increase nitrogen amounts, there was an overall decline in results up to 4.65g/collection. This may be due to increased amounts of volatile NH4CI formed from ammoniacombining with added HCI. Vortexing remains necessary to obtain clinically reliable TUNS. butadjusunem of pH and heating should be avoided.

94

A COMPARISON OF INDIRECT CALORIMETRY AND THE DIRECT FICK METHOD FORCALCULATING ENERGY EXPENDITURE. P.A. Kearney, MD, W.E. Pofahl, MD, K. Annis,MS, RD, J. Zeigler, RN, BSN, T. Floore, RN, BSN, S.B. Johnson, MD Department ofSurgery, Section of Trauma and Critical Care, University of Kentucky, Lexington,Kentucky

The need for skilled personnel, costly equipment, and technical considerations limitthe use of indirect calorimetry (IC) for the measurement of energy expenditure(REE) in critically ill patients.This study compared open circuit IC (REEIC) withcalculation of REE utilizing the Ligget modification (REEFick=COx[Hgb]x(Sa02-SvOp)x95.18) of the Fick equation in a heterogeneous group of 15 critically ill

patients. Cardiac output (CO), arterial (Sa02) and mixed venous (SvG2) oxygensaturation measurements were obtained from the pulmonary artery catheter at thebeginning and end of the IC study. MeanREEIC was 2225 1 471 Kcal and meanREEFick was 2089 t 471 Kcal. (p=0.1)The coefficient of correlation was

0.798. (p< 0.001)We conclude that REEFick is faster,

less costly, and can be utilized in

patients receiving high inspired oxygenconcentrations. REEFick is as accurate asREE obtained by open circuit IC andeliminates the difficulties encounteredwith the performance and interpretationof IC results.

95

A SIMPLE METHOD FOR STABLIZING INSPIRED OXYGEN CONCENTRATION DURINGMETABOLIC MEASUREMENTS. R.D. Branson, RRT, K Davis Jr, MD and D.J.Johnson, MD Department of Surgery, University of Cincinnati MedicalCenter, Cincinnati, OH.

Maintenance of a stable FI02 during metabolic measurements in mech-anically ventilated patients is essential. This is normally accomplish-ed by placing an air-oxygen blender between wall gas sources and theventilator. We studied FI02 stability delivered via a Puritan-Bennett7200a ventilator during normal operation, with an external air-oxygenblender and with a mixing chamber placed in the ventilator’s inspiratorylimb. The ventilator was operated at FI02’s of 0.40, 0.60 and 0.80 andminute ventilations (VE) of 4, 8, and 12 L/min. FI02 was continuouslyrecorded via an Amtek S-3 precision analyzer. FI02 stability at anF102 of 0.60 and 3 levels of VE are shown in the Table.

This demonstrates that as VE increases, F102 is less stable and thatthe use of a mixing chamber in the inspiratory limb is a suitablealternative to an external blender. Cost of the mixing chamber is $19vs $600 for a blender and technician time to set-up is also less withthe mixing chamber (1 minute vs 5 minutes).

96

ENERGY EXPENDITURE IN VERY-LOW-BIRTH-WEIGHT MECHANICALLYVENTILATED INFANTS. D.H. Adamkin MD, P. Radmacher BS, R.

Klingbeil MA RD, T. Samiec MD, T. Hill BS. University ofLouisville, Department of Pediatrics.

Seventeen VLBW infants with hyaline membrane disease onmechanical ventilation provided 38 studies using acomputerized indirect calorimeter over the first 7

postnatal days. Energy expenditure (REE) each day forthose infants studied was related to their energy intake(EI) that day. Shown below are mean + lSD.

n~,. n 1 9 ’:I A ~ r,

Mean REE for the entire 7 days inclusive was 56+15.REE-EI for the first 4 days was -31 cal/k/d and nearlyisocaloric the last 3 study days.

The data confirms the negative caloric balance thatcritically ill VLBW infants experience the first days oflife relating to glucose intolerance and the reluctance ofmany to initiate TPN with lipid. Also the variation inindividual infants REE suggests the need for individuali-zation of nutritional support.

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97ESTIMATION OF THE RATE OF CARBON DIOXIDE PRODUCTION USING [13C]-BICARBONATE. D.L. Habash, H.S., C. L. Kien, M.D., Ph.D., C. A.

Horswill, Ph.D., and A.R. Coggan, Ph.D. Dept. Peds., Coll. Hed. andthe Exercise Physiology Laboratory, Sch. of Health, Rec., and Phys. Ed.,The Ohio State Univ. and Children’s Hospital, Columbus, OH and Sectionof Applied Physiol., Washington Univ. Sch. Med., St Louis, MO.

Methods are needed for assessing CO. production and energy expenditureover periods of several hours during exercise or in sick patients. Therate of appearance of CO, (RaCO,), measured by isotope dilution, mightclosely approximate CO. production measured by indirect calorimetry(VCO,) especially during exercise since the rate of dilution of labelwould be high in this condition relative to isotope exchange. Twostudies were conducted to estimate RACO, in adults during stationarycycling at 50-60% of their maximum 0. consumption. RACO, was estimatedfrom the rate of administration of tracer CO. (&dquo;C-bicarbonate) and theplateau 13C enrichment of breath CO.. In the first study, conducted in8 subjects receiving repeated oral doses of 13C-bicarbonate, VC02 (909± 102 pmol/kg/min) was 78% of RACO, (1169 ± 425). Two subjects departedfrom the outpatient protocol. In the subgroup of 6 subjects, RACO,correlated with VCO. (R-0.896; P-0.016), and when the mean of the ratioof VC02 to RACO, was used to correct individual values of the RaCO.. meanRaCO2 was 101% of mean VCO,. In a second study of 4 subjects receivingan intravenous infusion of tracer, mean RACO, was 102 ± 5.7% of VCO..We conclude that RaCO. may be a useful index of VCO. or energyexpenditure during exercise or in sick patients over periods of severalhours. (Support: NIH Grant Nos. 11D19773 and RR00954).

98

ENERGY EXPENDITURE IN HEPATOCELLULAR CARCINOMA PATIENTS.Wei-Jao Chen, MD, MPH, DMSc, Yuan-Chang Chung, MD, Po-Huang Lee,MD, and Chue-Shue Lee, MD, Department of Surgery, College of MedicineNational Taiwan University. Taioei. Taiwan. R.O.C.

An Increase in resting energy expenditure (REE) is considered tocontribute significantly to the weight loss in cancer patients. Thealternations of basal metabolism of various neoplasms, however, are notinvariable. Twenty-five patients with hepatocellular carcinoma (HCC), and22 controls were chosen to evaluate the changes in REE of HCC patients.REE was measured by the use of indirect calorimetry. The oxidation ratesof endogenous substrates, such as carbohydrate, fat, and protein, were alsomeasured. Results of the study demonstrated a significant elevation of REEin the HCC group than the control group (23.0i0.6 Kcal,&dquo; ,/day vs 21.130.5Kcal/kg/day, p <0.05). When tumors were divided i..to three groupsaccording to their size, REE of large and medium size groups were higherthan those of small size group (24.1:tO.7 and 23.4tO.7 vs 19.1*1.2Kcal/kg/day, p<0.05). REE in HCC patients with or without liver cirrhosis,however, showed no difference (23.0±0.8 vs 23.3tO.9 Kcal/kg/day, p<0.05).Also, no significant difference in relative ratios of energy expenditure fromthe three main substrates: carbohydrate, fat, and protein, between the HCCpatients and the controls were observed. These results suggest that HCCresult in an increase in REE and the Increase in REE is related to thetumor size. Cirrhosis of liver do not contribute to the changes in REE.

99

DECREASED HAND GRIP STRENGTH IN ALLOGENEIC BONE MARROW TRANSPLANTPATIENTS. J. Beck, MPH, RD, E. Peters, MD and R. Champlin, MD Departments of Nutrition,Medical Specialties and Hematology, University of Texas M. D. Anderson Cancer Center, Houston,TX.

This swdy was undertaken to evaluate the effect of allogeneic bone marrow transplantation(ABMT) onnutriûonal status and hand grip strength (HGS).

METHODS: Study population consuted of 31 patients with hematologic malignancies assessedprior to ABMT with conventional nutritional assessment (NA) tools (weight, arm musclecircun~fercnce (AMC) and albumin) and HGS by dynamometry. In addifion, a subgroup of 10Patients had REE mcasureel (MREE) with indirect calorimetry prior to ABMT. These 10 patientswere followed for 30 days with daily caloric/protein intakes and evaluated post ABMT for changes inweight, AMC and HGS.

RESULTS: Prior to ABMT, patients had normal 96 ideal body weight (101 t 4.4%), serumalbumin (3.68 t 0.11 g/dl). and 96 Standard(STD) AMC (93.4 t 1.7396). However, 9fuSTD HGSwas decreased to 67.7 t 3.36 96 of normal.

Nutrition support was delivered at 2296 (28.8 :t 3.3 kcal/lg ) above MREE (23 f 1.5 kcal/kg);protein at 1.0 t 0.1 1 gm/kg.

CONCLUSIONS: (1) Pre ABMT patients exhibit decreased HGS not rel1cclCd conventionalNA tools. (2) A significant decline in IIGS occurred in the subgroup popliin d. , ~te adcqumcnutritional support and was not reflected by changes in weight or AMC. (3) Dccrc..B...:d I IGS mayreflect significant impairment of muscle function not accounted for by convenuonal NA tools inABMT patients.

loo Nutrition SupportEFFECT OF ALBUMIN ADMINISTRATION ON VISCERAL PROTEIN MARKERS INPATIENTS RECEIVING PARENTERAL NUTRITION. R.O.Hrown,PharmD, J.F.Binkley,BS,S.L.Wojtysiak,PharmD, K.A.Kudsk,MD, Departments of Clinical Pharmacy and Surgery,Universitv of Tennessee, MemDhis. TN.

Serial monitoring of visceral protein concentrations during specialized nutrition support isbecoming common practice to assess efficacy of therapy. Because some hypoalbuminemic patientsmay receive exogenous albumin during parenteral nutrition (PN), we studied the effects of albuminadministration- on serum concentrations of frequently used visceral proteins during PNadministration.

Thirty hypoalbuminemic (<3.0 g/dL) patients who required PN (D25W + AA S~o) wererandomized to receive PN plus albumin 25 g/L (treatment) or PN alone (control). Serumconcentrations of prealbumin, fibronectin, and transferrin were measured at baseline and after fivedays of PN.

Each group contained 15 patients and they were well matched for weight, DEE, dose of PN, andbody mass index. The control patients were slightly, but significantly older than the treatmentpatients (59.0:t 10.8 vs 46.3:t 14.0 years, p < 0.05). The visceral proteins appear in the Table (meant S.D.).

I -I... I -

The serum concentrations of fibronectin and transferrin increased significantly from baseline onlyin control patients. Significant improvement in prealbumin concentrations were observed in bothgroups between days one and five. Serum albumin increased in both groups, but was significantlyhigher in the treatment group at day 5 (2.3t0.4 vs 3.5 :to.7, p<0.01). Supplementation withhuman albumin results in a blunting effect of some visceral protein concentrations in

hypoalbuminemic patients receiving PN.

101

EFFECT OF POSTURE ON SERUM ALBUMIN LEVELS. M. L. Sauer, PharmD and J. W.Taylor, MD, Glen Oaks Hospital, Glendale Heights, IL.

This study was performed to document the effect of posture on serum albumin in healthyindividuals. This may hep explain the rapid fall in serum albumin levels often seen inhospitalized patients between admission and subsequent values, since malnutrition.defective protein synthesis, or excessive catabolisrn would not cause a decline of this extent.

Thirty-eight volunteers completed a medical history to identify conditions which wouldeffect protein synthesis or its elimination. All were screened for proteinuria, anemia, and baseline chemistry abnormalities. Sixteen women, aged nineteen to thirty-six years, and fourteenmen, between twenty-seven and forty-one years old, completed the study, following theelimination ofeight volunteers.

Each subject was asked to be in bed a minimum of six hours prior to the supine blood drawand to be upright, engaged in normal daily activities for a minimum of four hours prior to asecond blood draw.

Following the blood sample collection. albumin levels were compared for differences insupine and standing levels. The statistics were compared for the females alone, the malesalone, and the combined groups. The resuks are statistical significant (p<0.001 in all cases).The average standing albumin level was 4.4 grams, and the average supine level was 0.4grams lower. The resuits were extremely consistent. Also, although the male subjects wereolder than the females, there were no differences between the sexes.

In conclusion. albumin levels were significantly bwer in supine volunteers, with an averagedrop of 0.4 grams from standing levels (p<0.OO1). Because this change is seen in healthyindividuals, we suspect that a portion of the fall in atbumin levels in hospitalized patients canbe attributed to a change in posture. We conclude that this albumin level reduction should betaken into account when interpreting albumin levels in hospitalized patients.

102REVISED CRITERIA FOR OBTAINING CENTRAL VENOUS CATHETER (CVC) BLOOD

#CULTURES. R.J. Shulman, HD, S. Phillips, RD, P. Gardner, RN, V.

Nichols, RN, T. Reed, RN, E. Havkins. KD. USDA/ARS Children’s Nutr ResCtr, Dept of Pediatrics, Baylor Coll of Med, and Dept of Pediatrics andPathology, Texas Children’s Hospital, Houston, TX.

In a preliminary study (JPEN 1991;15:36S) we determined what ap-peared to be an adequate amount of blood to discard before obtaining aCVC blood culture. To test this hypothesis in a larger cohort of pa-tients, we prospectively cultured the blood normally discarded from CVCpatients and compared culture results with those of the actual bloodculture. Blood was aspirated from the CVC (infants 0.3 ml, children 1.0ml) and discarded. Two further aliquots (2nd and 3rd) were obtained andcultured (infants 0.5 ml, children 1.0 ml). We determined the sensiti-vity (SENS), specificity (SPEC), and positive predictive value (PPV) ofthe 2nd aliquot by comparing its results with that from the 3rd (thatusually cultured). RESULTS: age 6.3 t 5.5 y (X±SD); 17 true positivecultures based upon the 3rd aliquot.

---- .... --n ._..

* at the time the culture was obtainedA CVC blood culture should be accurate in patients not receivingantibiotics if blood is discarded in the amounts of 0.3 ml (infants)or 1.0 ml (children). An accurate culture in patients receiving antibi-otics, however, may require a larger aliquot of blood to be discarded.

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103

TIIE ASSESSMENT OF BODY COAIPOSITION BY SKINFOLD ANTHROPOMETRY AND>;t0-ELECTRICAL IMPEDANCE TECHNIQUE.1. Dc Lccuw, MD PhD, G. Vansant, Dr Sc, L. Van Gaal, MD, PhD, Department of Endocrinoto-gy, Metabolism and Clinical Nutrition, University oCAntwcrP, Belgium.

Body composition is an important parameter of nutritional status in different discascs.Numerous methods are available to assess body composition. 1 fowcvcr, all techniques arc subjectto considerable error, as there are a variety of technical problems associated with each. Only fewmethods arc suitable in clinical practice. Bio-clectrical impedance (BI) seems promising for clini-cal usc bccausc it is noninvasivc, takes only a few minutes and requires no active collaboration ofthc patient. In this study, we com frarc BI with skinfold anthrotromclry. m was measured in stand-ardi7.Cd conditions and age- and scx-specific equations were used to calculate body fat. Skinfoldswcrc measured at four sitcs (biccps, triceps, subscapular and supra-iliac) and body fat was dctcr-mined with the tables of Durnin and Womcrsly. It is known however that thc measurement ofskinfold thicknesses, especially in the older and obese patients, can give some technical problems.Body Cat was measured in 449 healthy persons (285 men and 164 women). Agc varied from IG-77ycars and BMI ranged from IG.7 to 46.1 kg.m-2. Percentage body fat range from 8.0 to 47.5% withthc skinfold technique and from O.G to 78.5% with Bl. Lincar regression analysis showed a signifi-cant positive correlation (r=0.84; P<0.0001). 1 lowever, plot analysis shows that skinfolds ovcrcs-timatc fat mass in the lower range and undercstimatc it for the o(>csc patients in comparison withBI. Onlywhcn thc BMI varicd between 25.0 and 30.0 kg.rra2, no significant difference was ob-served between thc two methods. In the lowcr range of BMI, BI shows a 13% lower fat mass incomparison with skin Colds; when thc BMI was greater than 30.0 kg.m-2, m gives a 15 % highcrresult. We conclude that in the total range, both methods are comparablc but careful intcrpreta-tion is nccessary in the cxtrcmc rangc of body fat.

104

COMPARISON OF WEIGHTED VERSUS UNWEIGHTED ENTERAL FEEDING TUBES FOREFFICACY OF TRANSPYLORIC INTUBATION. L Lord, RN, A Weiser-Maimone, RD,M Pulhamus, RN & HC Sax, MD. Nutritional Support Service & Dept. Surgery,University of Rochester School of Medicine and Dentistry, Rochester, NY.

.,_...___ -1 ------ 1 -1 I--,--- 1.-1-- ___~..___ I-

rcoui~ne r.ranspy or~c p~acemenL OT Teeuing l.UDeS reuuces ilSplril1.10n in

ICU patients. Spontaneous passage eliminates the need for radiologic orendoscopic intervention. It is unclear if the additio....f a weight to theend of the tube or if the use of the prokinetic agen. metoclopramide inconventional dosage (10 mg) improves spontaneous transpyloric placement.Methods: In a randomized, prospective trial, 39 ICU patients (age > 2 yrs)had a total of 50 nasoenteral tubes placed after intravenous metoclopra-amide (20 mg in adults, 2 mg/kg in children). The tubes were 8 French indiameter with either a weighted end or an unweighted bullet tip. Tipposition was confirmed radiographically within four hours after blindplacement,and at one and two days if spontaneous passage had not occurred.

Tranznvlnric Pncitinn

A subsequent trial utilizing the unweighted tube with only 10 mg ofmetoclopramide achieved passage in significantly fewer patients. Thecombination of a higher dose of metoclopramide and a tapered, unweightedfeeding tube achieved transpyloric position in over 90% of ICU patients,obviating the need for additional intervention.

105

TRACHEAL GLUCOSE AS A DETECTOR OF ENTERAL FEEDING ASPIRATION. G.C.Kinsey, RN, MS, CNSN, M.J. Murray, MD, PhD, S.J. Swenson, MO, and J.M.Miles, MD. Mayo Clinic, Rochester, MN.

it has been suggested that measurement ot glucose (G) in tracheal I

secretions (TS) may be useful to detect tracheal aspiration of enteraltube feeds. However, standard tube feeding formulae contain very littleG monomer (< 2% of total carbohydrate), and since most methods formeasurement of G do not detect G polymers, the sensitivity of such a

method for detection of tube feed aspiration could be questioned. Inthis study, we measured G in the TS of 15 enterally-fed (EF) and 15nonenterally-fed (NEF) tracheal intubated patients. G concentration wasmeasured on an ultrafiltrate of TS using a YSI Glucose Analyzer. G wasdetermined on - 6 and 3 TS samples in each EF and NEF patient, respec-tively. In a subset of patients, serum G was measured within 6 hr of TSsampling (23 observations). The incidence of aspiration pneumonitis(AP) was determined in the EF by daily chest x-ray and observation forfever and leukocytosis. Comparison between groups was performed withStudent’s t-test and chi square analysis with Yates Lorrection, whenappropriate. TS G concentration was 66+14 and 105+18 mg/dl in EF andNEF, respectively (p=NS). A significant correlation between serum andTS G (r=0.39, p<0.05) was observed. None of the EF patients (0/15)developed AP. Thus, TS contain surprisingly high G concentrations, bothin EF patients without evidence of AP and in NEF patients. Theconcentration of G in TS appears to be determined, at least in part, byambient extracellular G concentrations. We conclude that measurement ofG in TS is of no benefit in monitoring intubated EF patients for tubefeeding aspiration.

106THE DEGREE OF GASTROESOPfiAGEAL REFLUX (GER) AS MEASURED BYpH MONITORING IN PATIENTS WITH NASOGASTRIC TUBES (NGT) VS.PERCUTANEOUS ENDOSCOPIC GASTROSTOMY (PEG). S. Aftahi, MD,L. Howard, MB, FRCP. Dept. of Medicine, VA Medical Ctr.and Albany Medical College, Albany, NY.__ - -.

PEG’s are frequently chosen over small bore feedingtubes, for long term enteral nutrition. Their relativesafety in regard to GER and hence the potential foraspiration has not been established in adults. In pediatricpatients the insertion of gastrostomies without anantireflux procedure, has in fact been associated withincreased GER.

We studied 4 men (av. age 79 yrs), all candidates forlong term tube feeding, by 24 hr distal esophageal pHmonitoring. This was done first on continuous NGT feedingand then the study was repeated one week or more afterinsertion of a PEG, again on continuous feeding with thesame formula. GER was assessed by 3 standard parameters andstatistical analysis was done with paired student t-tests.RESULTS: NGT PEG

Mean Range Mean Range p ValueReflux Episodes 16.7 6-31 65.2 36-91 0.01

Episodes >5 Min. 1.5 0-3 6.2 1-15 0.2% Time pH < 4.0 4.0 0.3-11.6 12.3 2.9-23.7 0.1

While normal values have not been established for GER insubjects on continuous enteral tube feeding, these resultsshow that a PEG was associated with significantly more GERepisodes than an NGT.

In conclusion; a patient with a PEG may have a higherrisk of aspiration than a patient with an NGT.

107ASPIRATING FOR GASTRIC RESIDUALS CAUSES OCCLUSION OF SMALL BORE FEEDINGTUBES. K.S. PoweU, MS, RDE, S.P. hlarcuard, hID and E.S. Farrior, PIiD, RD, Nutritioa SupportTeam, University Medical Center and Department otNutritiun, East Carolina University, Greenvilk,North Carolina.A frequent mechanical problem that is encountered with small bore feediug tubes (SBFT) (I

French) is kuneoal obstruction of the tube. It has been observed that most inuwt protein formulaswill clot when acidified to a pH < 5.0. The purpose of this study was to compare We occlusion ratewhen gastric residunlc (pH=2.0) were checked to occlusion rate when ga.tric: residuals were notchecked. Patients receiving iatact protein formula through SUET with the tips termÍl1lltÎD& in thestomach were included in the study. Residuals were checked in Group A every 4 hours and residuabwere not checked in Group B patients. FüteeD patients in Group A were followed for a total of 131patient days on feeding. Thirteen patients in Group B were followed for a total of IS4 patient dayson feeding. Ten occlusive episodes occuced in Group A (’-Type I: nurse able to restore pateocy, 3-Type II: researcher used activated pancreatic enzyme to unclog tube, I-Type Ell: tube had to bepulled). Ouly I-Type H occlusion occured in Group B.

~ , --

i --

_

i I I _

I -

I _ _ _,ere was signifwance difference (p=0.0171, alpha a = . between occlusion rate in roup ps

compared to Group B. We conclude that aspirating for gastric residuats through SBFR increases thechance for tube occlusion. We recommend to a~oid aspirating for gastric residuah~ through SBFf.

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