Subacute endotoxemia in dogs with experimental cirrhosis and ascites: effects on kidney function.

Abstract

To study the effect of low-grade continuous endotoxemia in normal and cirrhotic dogs, osmotic minipumps were filled with Escherichia coli endotoxin, implanted subcutaneously and arranged so that the endotoxin could be infused intravenously over a 7-day period in doses ranging from 2.5 to 100 micrograms/h. Observations were made at 3 and 7 days postinfusion. In normal dogs (N = 9), there was no effect on cardiac output or arterial pressure when doses as high as 50 micrograms/h were delivered into the circulation. Neither was there an effect on inulin or p-aminohippurate (PAH) clearances. At doses of 100 micrograms/h, dogs suffered a marked decrement in cardiac output, blood pressure, and renal perfusion and became lethargic at 3-7 days. In cirrhotic dogs, doses of 25 micrograms/h which had no effect in the control dogs, caused a significant decline in the glomerular filtration rate (59-21.5 mL/min) and CPAH (147-66 mL/min) at a time when cardiac output and blood pressure remained normal. At doses of 50 micrograms/h, cardiac output and blood pressure declined markedly and the dogs deteriorated quickly following 3-5 days of endotoxin. When endotoxin (25 micrograms/h) was given to dogs with acute biliary obstruction (serum bilirubin = 9.8 +/- 0.1 mg/dL) or to dogs with chronic thoracic caval constriction (which produced portal hypertension and ascites), no effect was observed on either central hemodynamics or renal perfusion. The selective renal vasoconstrictor effect observed in cirrhotic dogs could not be abolished by intravenous phentolamine or propranolol, inhibitors of alpha- and beta-adrenergic activity, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)