Fkl. Chan et al., THE EFFECTS OF LIVER-TRANSPLANTATION AND CYCLOSPORINE ON BILE FORMATION AND LIPID-COMPOSITION - AN EXPERIMENTAL-STUDY IN THE RAT, Journal of hepatology, 28(2), 1998, pp. 329-336
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.