Influence of liver transplantation and cyclosporin on bile secretion--an experimental study in the rat.
Bile secretion is reduced after liver transplantation. It has been suggested that this is due either to the effect of cyclosporin or to the damage to the liver graft during preservation and reperfusion. The aim of this study was to explore the influence of cyclosporin as well as of liver transplantation on bile secretion. Bile flow was studied in an experimental model in the rat. In syngeneic liver-transplanted animals, the bile flow was increased compared to the bile flow in the control group (1.29 +/- 0.09 ml/h vs 0.66 +/- 0.03 ml/h; P < 0.01), mainly due to an increased bile acid-independent flow (0.76 ml/h vs 0.50 ml/h; P < 0.01). The findings in the liver-transplanted rats contrasted with those in a group of nontransplanted animals treated with cyclosporin. Cyclosporin treatment resulted in a reduced bile acid-independent fraction (0.37 ml/h vs 0.50 ml/h, P < 0.05) of the bile flow, although no biochemical signs of hepatotoxicity were present. This reduction in the bile acid-independent fraction could, however, not be demonstrated when cyclosporin was given to a group of liver-transplanted rats, although a reduced total bile flow was recorded in the 1st hour measurements. In contrast to previous studies, we found that the cyclosporin vehicle (Cremophor EL), when administered chronically, induced a higher bile flow than that in the control rats. This effect was not seen in the transplanted rats. Our findings in this experimental rat model indicate that cyclosporin will influence and reduce bile secretion and bile acid secretion even if no other signs of liver dysfunction are present. On the other hand, the preservation and reperfusion in this model resulted in an increased bile flow, while bile acid secretion remained constant.
Svensson
G
G
Department of Surgery, Sahlgrenska University Hospital, Göteberg, Sweden.
Holmberg
S B
SB
Friman
S
S
D000818:Animals; D001646:Bile / Q000187:drug effects / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000032:analysis; D002779:Cholestasis / Q000139:chemically induced / Q000503:physiopathology; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects; D016031:Liver Transplantation; D008954:Models, Biological; D009929:Organ Size; D051381:Rats; D011920:Rats, Inbred WF
D001647:Bile Acids and Salts; D016572:Cyclosporine