Improvement of renal hemodynamics in endotoxin shock with dopamine, phenoxybenzamine and dextran.

Linda L. Sluibour, Rlobert D. Lindeman, Linda T. Archer, _ Su Utsin Tung and Lerner B. 11inshaw Improverent of Renal Hemodynamics in Endotoxin Shock with Dopamine Phenoxybenzainine and Dextran f The effects of dopamine were evaluated on the renal hemodynamics of dogs L endotoxin shock. In control animals receiving endotoxin only, mean systemic zxterial pressure decreased to 60%, renal blood flow decreased to 51%, renal resistznce increased to 116%, glomerular filtration rate decreased to 9% and urine flow decreased to 18% of control values. Preand post-treatment of *shocked aninals with dopamine showed no significant improvements in any of the * esu-ed parameters. Post-treatment with a combination of phenoxybenzamine (I mg/kg), dextran (20 cc/kg) and dopamine (mean infusion rate of 38 ug/kg/min) 1 significantly changed the measured parameters in endotoxin injected animals. In this group, mean systemic arterial pressure was 65%, renal blood flow was 128%, renal resistance was 47%, glomerular filtration rate was 29% and urine flow was 117% of control values at the termination of the dopamine infusion. Thirty minutes following termination of the dopamine infusion, mean systemic j arterial pressure was S9%, rnlblood flow was 691, renal resistance was 761, glaerular filtration rate as 19% and urine flow was 44% of control values. jThese findings show that dopanine significantly improves renal hemodynamics In endotoxin shock only when phenoxybenzamine is given to block the constrictor acticn of dopamine and when dextran is administered for volume replacement con,-co:-,Itrtlv with dopra-ine infusion. Endotoxin shock can be fatal to clinical subjects if it causes irreversible dar-.ge. Even after hemodynaxic function has been improved, the patient may die in renal failure. Dopaine (3,4-dihydroxyphenylethylamine) appears to benefit patients in various shock states (MacCannell at aZ., 1966). In hemorrhagic shock, for exaiple, dopamine improves heart (Carvalho at aZ., 1969) and kidney (Gifford at al., 1968) function. Studies from this laboratory, using dogs shocked with endotoxin, have shown that dopamine increases venous return independent of a direct effect on the heart (Shanbour and Hinshaw, 1969a); the liver being a primary site of its action. Dopamine produced a marked release of blood both in the nonal and shocked isolated liver preparations (Shanbour and FHishaw, 1969b). Moreover, McDonald at aZ. (1964) reported that dopamine increases the renal plasma flow in normal subjects and patients in heart failure. M Nay at al. (1965) pointed out the unique ability of dopamine to produce femoral artery corstriction and, at the same time, renal vasodilation. Most other agents previously reported to increase renal blood flow also increased femoral blood flow McWNay and Goldberg, 1965). Because beta-adrenergic blocking agents fail to interfere with its renal vasodilating properties Od;Nay at al., 1963), dopamine probably acts on an undefined receptor in the kidney (Yzyer at al., 1967; Goldberg at aZ., 1968; Yeh at aZ., 1969). Such a receptor has been suggested to exist (Eble, 1964) in the mesenteric vascular bed of the dog. Dopamine increases urine flow but the increase is not dep t upon systeic hmodynamic changes fMyer at aZ., 1967). Because of the previously described effects of dopamine, studies were conducted to determine its action on renal hemodynamics in the endotoxinshocked nirmal.