Formation of biliary thrombi in protoporphyrin-induced cholestasis in perfused rat liver

The effect of bile acids on the formation of biliary thrombi in protoporphyrin-induced cholestasis was determined by perfusing isolated rat livers with taurocholate, chenodeoxycholate and ursodeoxycholate with and without protoporphyrin. Protoporphyrin-induced reduction of bile flow was similar in the presence of each bile acid. The cholestasis was greater at high doses (2,000 to 10,885 nmol) than at low doses (1,500 nmol) of protoporphyrin, unrelated to the amount of lactate dehydrogenase released into the perfusate, and it was not altered by increasing bile acid infusions. Bile acid excretion was inhibited by high protoporphyrin doses. Periportal birefringent pigment deposits were seen in canaliculi and ductules when the biliary protoporphyrin concentration exceeded 161 nmol/ml, 345 nmol/ml and 1,036 nmol/ml for ursodeoxycholate, chenodeoxycholate and taurocholate, respectively; or, when the protoporphyrin (nanomole) to bile acid (micromole) ratio exceeded 3.23, 7.03 and 23.43, respectively. The maximal ratio of ductular deposits to portal tract deposits examined was 0.9. Electron microscopy showed these deposits were associated with canalicular thrombi. Thus, biliary thrombi were produced by infusion of bile acids and protoporphyrin. The occurrence of thrombi varied with bile acid structure. Explanations for this finding are speculative. The presence of periportal thrombi, however, did not influence the degree of functional cholestasis.