Importance of perfusate hematocrit for insulin- and glucagon-induced choleresis in the perfused rat liver.

Insulin and glucagon stimulate bile production in the intact rat without affecting the biliary excretion rate of bile acids. This effect was not demonstrable in rat liver perfused with human erythrocytes suspended in a Krebs-Henseleit-bicarbonate buffer at a hematocrit of about 18%. The present experiments demonstrate that the choleretic effect of insulin and glucagon observed in the intact rat is reproducible in perfused rat liver if the hematocrit of the perfusate is raised to about 35%. An increase in perfusate hematocrit is also accompanied by a 65% rise in hepatic oxygen consumption and a 27% rise in the basic production of bile, due to an increase in bile acid-independent bile formation. The mechanism by which these changes in perfusate hematocrit influence the function of the perfused liver is obscure. The difference in oxygen content of the perfusates appears to be without importance. Judged from lactate-pyruvate and beta-hydroxybutyrate-acetoacetate ratios of perfusate as well as electron microscopy, maldistribution of perfusate flow and local hypoxia were not evident in perfusions with low hematocrit. A part of the increase in hepatic oxygen consumption seen with a rise in perfusate hematocrit can, however, be explained by an increase in lactate supply from erythrocyte glycolysis. The results stress the importance of perfusate hematocrit for optimal bile production of the perfused rat liver.