Mechanisms of liver adaptation to prolonged selective biliary obstruction (SBO) in the rat

To determine changes which occur in selective biliary obstruction (SBO), we studied male adult Fischer rats after one month of either SBO or selective biliary cannulation (SBC) of the median lobe duct (MLD). In rats with SBC the ML was obstructed with a sealed PE-10 catheter placed in the MLD. One month later at laparotomy the ML was either drained or not drained for 30 min before the injection of 200 microCi [99Tc]DIDA (2,6-diethylacetoanilido-imino-diacetic acid). Bile was collected and biopsies of the obstructed ML and non-obstructed right lobe (RL) were taken at 1, 3, 10 and 30 min. Serum bile acid concentrations were higher in SBC not drained rats than in control as were hepatic bile acid concentrations. The latter, however, did not achieve statistical significance. In SBC-drained rats biliary bile acid secretion from the obstructed lobe was lower than that from the non-obstructed lobe for 30 min after the release of obstruction but was thereafter the same. Hepatic DIDA levels in both the obstructed and non-obstructed portions of liver from SBO animals were higher than in liver from controls, despite normal DIDA biliary excretion. This is in part explained by increased cytosolic binding of DIDA. In rats with SBO the MLD was simply ligated and transected. After one month uptake kinetics of [14C]taurocholate in freshly isolated hepatocytes from obstructed and non-obstructed lobes were similar suggesting that no major impairment of BA uptake occurs. We conclude that cholestasis is still present after 30 days of SBO in spite of the presence of interlobular biliary connections. The observed increased hepatic storage capacity for DIDA is probably an adaptive mechanism in mild chronic cholestasis.