LOSS OF ZONAL HETEROGENEITY AND CELL POLARITY IN RAT-LIVER WITH RESPECT TO BILE-ACID SECRETION AFTER BILE DRAINAGE

Functional liver heterogeneity depends on the current perihepatic environment. The effect of chronic bile drainage on hepatic secretion of bile acids in periportal and pericentral rat liver cells was studied. After 4 days of biliary drainage, rat livers were perfused in vitro in either forward (through the portal vein) or backward direction (through the vena cava) in single-pass arrangement with taurodeoxycholate (32 nmol · min-1 · g liver-1). Tritiumlabeled taurodeoxycholate (0.5 μCi) was injected as a pulse to determine uptake, biotransformation, and hepatic secretion. During bile drainage, bile flow fell from 1.8 (μL · min-1 · g liver-1 to ≈ 0.6 μL · min-1 · g liver-1. Bile acid secretion rate dropped from initially 50 nmol · min-1 · g liver-1 to ≈ 5 nmol · min- · g liver-1 within 24 hours and remained at this level for the next 3 days. After bile drainage, liver histology was well preserved and was indistinguishable from controls. During liver perfusion of controls in both directions, bile flow exceeded 1 μL · min-1 · g liver-1, whereas bile-drained animals demonstrated a bile flow between 0.4 and 0.6 μL · min-1 · g liver-1. In contrast to controls, the drained-animal liver did not excrete label exclusively in bile but simultaneously excreted about one third back to the perfusate medium (regurgitation). Biliary bile acid recovery within the first 10 minutes after 3H-taurodeoxycholate bolus injection was 90% (of label taken up) in forward-perfused controls but only 40% in forward-perfused drained animals. Backward-perfused control and drained animals excreted about 20% in this time interval and did not differ significantly. T50, the time to excrete 50% of label taken up in bile or both bile and effluent, increased from 4.3 ± 0.36 minutes (SD) in forward-perfused controls to 13.2 ± 2.28 minutes in forward-perfused, drained animals. T50 of backward-perfused controls and backward-perfused drained animals did not differ significantly (17.8 ± 1.75 minutes vs. 21.0 ± 3.95 minutes). In conclusion, chronic bile drainage reduces liver heterogeneity with respect to velocity of bile acid excretion and cell polarity is lost with respect to hepatocellular translocation of bile acids. © 1991.