JOURXAL OF SURGICAL RESEARCH, 11, 515-517 (1971)

Preliminary Report

EFFECTS OF PLURONIC F 68’7 POLORALKOL, ON VASCULAR RESISTANCE IN VIVO

JOHAN HOIE, M.D. AND WORTHINGTON G. SCHENK, JR., F.A.C.S.

Pluronic F 68@ has been introduced in medicine to reduce the increasing vascular re- sistance encountered during ex-vivo perfusion of excised organs, the spleen in particular [l]. It is a non-ionic polyol surface-active agent utilized for stabilizing fat emulsions for intra- venous application. As an adjuvant during ex- tracorporeal circulation it minimized hemoly- sis and denaturation of protein in the extracor- poreal circuit, platelet adhesiveness and fat embolism are reduced and intravascular “sludging” prevented [2]. The present study was undertaken to investigate whether Plu- ronic F 68@, poloralkol, has flow promoting properties in vivo.

MATERIAL AND METHODS

Seven healthy mongrel dogs of either sex with mean weight 17.6 (13-19) kg. were used in the study. General anesthesia was induced with intravenous pento-barbital (25 mg/kg) and maintained with small doses when neces- sary. The dogs were intubated and ventilated with room air by a piston type ventilator. Aortic and central venous pressures were mon-

From the Department of Surgery, State University of New York at Buffalo and the Surgical Research Laboratories at the Edward J. Meyer Memorial Hos- pital, Buffalo, New York 14215.

Supported in part by a Grants-in-aid from the National Heart Institute (No. HE-03181) of the U. S. Public Health Service and the Institute of General Medical Sciences (No. GM-15768).

itored via properly placed catheters connected to strain gauge pressure transducers. Cardiac output, renal and superior mesenteric artery flow were computed by electromagnetic square-wave flowmeters.? Snugly fitting flow probes were placed on the ascending aorta through a left thoracotomy and on the supe- rior mesenteric and left renal arteries through a left flank incision. Zero flow was defined by sling occlusions of the smaller vessels and by the diastolic quiet interval in the aorta. Pres- sure and flow signals were amplified and re- corded on a multichannel direct writing poly- graph.

After the exprimental set up was com- pleted, a period of stabilization was allowed. Baseline measurements included hemoglobin concentration, arterial oxygen saturation and packed cell volume. The latter was measured at set intervals during the experiment. Vascu- lar resistance was calculated in arbitrary units, PRU

PRU = mean arterial pressure mmHg/mean

arterial flow ml/mm

Protocol

4 dogs were given 5 mg poloralkol/kg body weight intravenously and observed for 2 hours.

3 dogs were given the same amount of polor-

t Carolina Medical Electronics, King, N.C.-Model 322.

515

516 JOURNAL OF SURGICAL RESEARCH, VOL. 11, NO. 10, OCTOBER 1971

Table 1. Changes following intravenous injection of 5 mg Pluronic F S&@/kg body weight to normal dogs

(n = 4) Means and range

Minutes after end of Pluronic P-68 infusion

Initial values 30 60 90 120

Mean aortic pressure mm Hg

Total body vascular resistance PRU

Renal vascular resistance PRU

Mesenteric vascular resistance PRU

Central venous pressure cm Hz0

Hematocrit

122 124 126 126 128 (115-130) (115-130) (120-130) (120-130) (124-130)

(*6%, (46:2 ) (4625) (4624) (465iO)

(46?6) (52%) (5578) (60% ) (56% )

(33Z4) (4cz4) (405i4) (42:4 ) (42:4 )

(8Y3) (8%) (8Y2.2) (723) (7% )

(3622 ) (36%) (36Z3) (36%) (3622 )

Table 2. Changes following intravenous injection of 6 mg Pluronic F 68@&1 body weight combined with in&a-aortic infusion of 76 NIHu thrombinikg over SO minutes

(n = 3) Means and range

Minutes after end of thrombin infusion

Initial values 0 30 60 90

Mean aortic pressure mm Hg

Total body vascular resistance PRU

Renal vascular resistance PRU

Mesenteric vascular resistance PRU

Central venous pressure cm Hz0

Hematocrit

117 (105-130)

(41%)

(43Z3)

(2GO)

(8% )

(38Z3)

114 (100-130)

(54Y2) 208

(165-230)

(2520)

(7-;o)

(3323)

alkol along with 75 NIHu thrombin/kg body weight in the descending aorta over 30 min- utes.

RESULTS

No influence on the total aortic blood flow or on the distribution of this blood to different regions studied was effected by Pluronic F 68@ in the “normal” dogs, nor was any change in hematocrit observed. The vascular resistance remained unchanged (Table 1).

In the thrombin-infused dogs significant changes in cardiac output and in the regional allocation of this blood flow was experienced. The renal vascular resistance increased sub- stantially while mesenteric blood flow was

115

(lW130)

(5CZO)

(65?30 )

(28Z2)

(8% )

(39Y3)

117 (110-130)

(48!6 )

(5::2 )

(28Z8)

(21)

(3923)

117 (m-130)

(48%)

(48!2 )

(3028)

(8% )

(3FS4L)

only slightly influenced (Table 2). These find- ings are in agreement with alterations induced in the dog by thrombin infusion alone [3]. Plu- ronic F 68@ did not appreciably lessen altera- tions in vascular resistance induced by throm- bin infusions.

COMMENTS

Poloralkol was remarkably inert when in- fused intravenously. It stabilized erythrocyte suspensions [2] as do dextrans, but demon- strated no volume expanding properties. The molecular weight of poloralkol is 8200 and 60 per cent of an injected dose is excreted in the urine within 1 hour [l]. As investigated by its influence upon vascular resistance, it did not

HOIE SXD SCHENK, JR.: PLUROXIC F68 517

improve the flow characteristics of blood in normal dogs.

Grower, Newman and Paton found that capillary flow was enhanced and aggregation of erythrocytes reduced by poloralkol in ex- perimental shock [4]. In our particular model we did not experience any reduction of the impairment of blood flow provoked by throm- bin infusion when the surfactant was com- bined with the infusion. Thrombin was given because it might produce in vivo some changes in blood similar to those occurring in the bub- ble oxygenator where addition of Pluronic F 68s has proven beneficial [2]. Hemolysis, platelet embolism and precipitation of fibrin caused by thrombin might, however, be in- duced through different pathways and with much greater impact than in the extra-corpo- real circuit.

Although the numbers of experiments were somewhat limited, the lack of response ap- peared clear enough that expenditure of fur- ther research resources did not seem justified.

SUMMARY

Pluronic F 68@ poloralkol, a surfactant proven beneficial in extra-corporeal circula- tion, in organ perfusions and in experimental shock did not improve the flow characteristics of blood measured by vascular resistance, renal and superior mesenteric blood flow in ei- ther normal or thrombin infused dogs in vivo.

REFERENCES 1. Moore, A. R., Paton, B. C., and Eiseman, B. Re-

duction of splenic vascular resistance during per- fusion by Pluronic F 68. J. Surg. Research 8:563- 556, 1968.

2. Miyauchi, Y., Inoue, J., and Paton, B. C. Adjunc- tive use of a surface-active agent in extra-corporeal circulation. Circulation (Supp 1) 33, 34:71-77, 1966.

3. Hoie, J., and Schenk, W. G., Jr. Hemodynamics of “Disseminated Intravascular Coagulation.” Effects of intra-aortic thrombin infusions on renal and mesenteric blood flow in dogs. Submitted, Archives of Surgery.

4. In Drucker, W. P. “What is new in surgery. Shock and metabolism.” Surg. Gyn. Obst. 132:234-238, 1971.