PATTERN OF BILE-ACID REGURGITATION AND METABOLISM DURING PERFUSION OFTHE BILE-DUCT OBSTRUCTED RAT-LIVER

Bile acid processing in the long-term, bile duct obstructed rat liver was studied ex vivo. Twenty four and 72 h, respectively, after bile du ct obstruction the isolated liver was perfused with tauro-deoxycholate (16 nmol/min per g liver) the bile duct still being closed. Uptake, m etabolism and regurgitation profile were traced by bolus injection of tritium-labeled bile acid; in addition, concurrent histological change s were examined by light- and electron microsopy. Ligation caused dila tation of the intrahepatic ductular branches and increased the serum b ile acid concentration to 740 +/- 75 mu M (controls: 16 +/- 2.12), rea ching its maximum within 24 h. At 16 nmol/min per g liver uptake rate was >96% in controls and in bile duct obstructed rats. Maximal uptake rates (assessed separately) differed between controls and bile duct ob structed rats (700 nmol/min per g liver vs, 460). Controls excreted mo re than 80% of labeled bile acid in bile within 10 min after bolus inj ection. Biliary recovery of label was virtually completed after 30 min , In bile duct obstructed rats excretion of label back to the perfusat e effluent (regurgitation) started quantitatively 5 min after bolus ap plication and peaked between 10 and 40 min; after 80 min, effluent rec overy was incomplete (about 60% of bolus injected), Biliary bile acids of controls consisted of about 20% taurodeoxycholate-metabolites; bil e acids in the perfusate effluent of bile duct obstructed rats of abou t 55%, The major metabolite in all animal groups was taurocholate; min or metabolites were tauroursocholate, tauro-3 alpha, 7 = 0,12 alpha-ch olanoic acid and '3-sulfo-tauro-deoxycholate. Histologically, inflamma tion and periportal edema were present after 1 day of bile duct obstru ction, After 3 days, marked proliferation of bile ductules was the dom inant histological feature, It is concluded that during initial bile d uct obstruction, bile acid processing is not altered, although ultrast ructural alterations occur early.