Changes in biliary secretion following sporidesmin poisoning in sheep

Abstract

Hepatic bile-flow rates, determined in sheep with an exteriorized common bile-duct loop which maintained the enterohepatic circulation of bile constituents, averaged 71·9 ml./hour (S.D. 24·7, from 54 measurements on 12 sheep). No significant diurnal variations in flow rates were found during the 24-hour periods examined. Interruption of the enterohepatic circulation by total drainage of bile resulted in a dramatic reduction in bile-flow rate during the first two hours of drainage after which a constant but low basal flow rate was maintained. After a single oral dose of sporidesmin at a rate of 1·0 mg./kg., bile flow decreased over the subsequent 14 days to a negligible flow. There was no abrupt cessation of bile secretion in the acute stages of poisoning. The early reduction in bile flow observed may be associated with acute inflammatory cholangiolitis in the first phase of the disease. The cessation of bile flow later observed in the second phase is associated with progressive obliterative cholangiolitis due to an exuberant granulation-tissue repair process. Bile analyses revealed that bilirubin continued to be excreted while bile secretion continued, but that alkaline phosphatase activity decreased in close parallel to decrease in bile-flow rate.