BILIARY HYPERPRESSURE IN RAT EXTRAHEPATIC CHOLESTASIS ALTERS HORSERADISH-PEROXIDASE BILIARY-EXCRETION

1. The authors investigated the effect of two extrahepatic cholestasis models (one by bile duct ligation and the other by choledocho-jugular fistula) on the hepatic clearance of horseradish peroxidase in male S prague-Dawley rats divided into four groups. 2. In groups A (n = 5 rat s) and B (n = 5), bile duct ligation was performed, while a choledocho -jugular fistula was created in groups C (n = 5) and D (n = 7). A 10 m g intravenous bolus of horseradish peroxidase was injected after 24 h (groups A and C), 48 h (groups B and D) or 1 h (Group E; five sham-ope rated rats). Serum and bile samples were then serially collected for 2 h. 3. In all groups, serum horseradish peroxidase levels increased so on after injection and then rapidly decreased, the curves being simila r. Biliary excretion increased for 30 min and then slowly decreased. T he highest horseradish peroxidase biliary concentrations and outputs w ere found in Group B followed by (Group A; both groups had significant ly higher levels than Group E. No difference was found between horsera dish peroxidase biliary excretion of groups C and D and that of sham-o perated rats. 4. When each group was considered separately, sampling t imes correlated with the corresponding ratios of bile/plasma HRP. Sign ificant differences were found between the relative slopes of groups A , B and E, but not between those of groups C, D and E. 5. In conclusio n, bile duct obstruction greatly affects the plasma-bile transfer of f luid phase markers, such as horseradish peroxidase, while single reten tion, caused by choledocho-jugular fistula, has no influence. The incr eased biliary hyperpressure related to the duration of cholestasis may account for the degree of horseradish peroxidase transfer which, in t urn, probably depends on an enhanced paracellular passage.