THE EFFECTS OF LIVER-TRANSPLANTATION AND CYCLOSPORINE ON BILE FORMATION AND LIPID-COMPOSITION - AN EXPERIMENTAL-STUDY IN THE RAT

Background/Aims: Hepatic graft dysfunction is a major management probl em in the early post-liver transplantation period, Our aims were to st udy how liver transplantation per se affects bile formation, and to in vestigate the role of cyclosporine in the pathogenesis of early graft dysfunction. Methods: Syngeneic liver transplantation used male Lewis rats, Two weeks after transplantation, the rats were randomly assigned to receive either daily subcutaneous injections of cyclosporine 10 mg /kg for 1 week (n=8), or daily saline injections (Placebo, n=8), 24-h bile collections were performed 18 h after the last injection, Eight n on-transplanted rats served as controls. Results: Liver transplantatio n pel se (Placebo) significantly increased basal bile flow (51%), part icularly that portion which was bile salt-independent flow (81%), but did not impair bile salt kinetics or biliary lipid composition, Cyclos porine reduced basal bile flow and bile salt-independent flow by 41% a nd 30%, respectively, Bile salt synthesis was 52% suppressed, leading to a 22% decrease in the bile salt pool size, The recycling frequency of the bile salt pool was unaffected, The drug inhibited bile salt (37 %) and phospholipid (23%) outputs; cholesterol secretion remained unal tered, This significantly elevated the cholesterol saturation of bile (25%). Conclusions: Liver transplantation per se is choleretic and doe s not impair bile formation or lipid composition in this inbred rat mo del, Parenteral administration of high-dose cyclosporine induces chole stasis by inhibiting bile salt secretion and BSIF. Bile salt synthesis is down-regulated and the bile salt pool size decreased, The drug adv ersely affects biliary lipid composition by differential inhibition of bile salt and phospholipid outputs relative to an unchanged cholester ol secretion.