Cholestatic effects of Escherichia coli endotoxin endotoxin on the isolated perfused rat liver

Abstract

The effects of Escherichia coli endotoxin on the function of the ex vivo perfused rat liver were examined in order to investigate the possible role of circulating endotoxin in the pathogenesis of cholestatic jaundice observed in humans with gram-negative bacterial infections. Endotoxin led to a dose-dependent impairment of bile flow and of sulfobromophthalein (BSP) excretion. The demonstration that indocyanine green excretion was also significantly decreased by endotoxin suggests that the impaired dye excretion was not due to an inhibition of BSP conjugation in the hepatocyte. Analysis of the kinetic data suggested that the effects of endotoxin were on the excretory mechanisms of the hepatocyte. These effects did not seem attributable to endotoxin-mediated changes in perfusate flow since a mechanical reduction in perfusate flow caused no decrease in the excretion of bile or BSP. The results of the present study provide supportive evidence for the hypothesis that circulating endotoxin can adversely affect hepatic function and may contribute to the production of intrahepatic cholestasis seen during bacterial infection. Hepatocyte injury by endotoxin, as judged by the leakage of enzymes from hepatocyte suspensions or from the perfused rat liver, could not be demonstrated.