Cyclosporin A in orthotopic porcine liver transplantation. Long-term survival after short-term treatment.
The aim of this study was to evaluate the efficacy of cyclosporin A (CyA) in prolonging graft survival after orthotopic porcine liver transplantation in mixed lymphocyte culture (MLC) mismatched couples. CyA was given intramuscularly for a period of 21 days, starting on the day before transplantation. In order to study the fate of the graft, frequent liver biopsies and blood samples were taken after transplantation. 4 pigs received CyA at a dose of 10 mg/kg/day, and 10 animals were treated with 20 mg/kg CyA per day. In the low-dose group 1 pure plasma cellular rejection was noted, while the grafts of 2 pigs showed a transient plasma cellular infiltration in the portal tract. By doubling the dose, only 1 out of 10 animals rejected the liver graft. The livers of the other 9 animals did not show any noteworthy histological sign of rejection, and also the liver function tests were normal. Total serum bile acids and routine liver function tests remained undisturbed in animals that accepted the MLC-mismatched graft and increased in cases of rejection. No nephrotoxicity was noted due to CyA treatment. The main complications encountered were infections leading to death in 4 CyA-treated pigs, while the liver graft was functioning well. Short-term treatment with CyA can overcome the rejection of a MLC-mismatched porcine liver graft and induces a state of long-term acceptance.
D000818:Animals; D001647:Bile Acids and Salts / Q000097:blood; D003404:Creatinine / Q000097:blood; D003524:Cyclosporins / Q000008:administration & dosage / Q000494:pharmacology*; D006085:Graft Survival / Q000187:drug effects*; D006650:Histocompatibility Testing; D008099:Liver / Q000473:pathology; D016031:Liver Transplantation; D007959:Lymphocyte Culture Test, Mixed; D013552:Swine
D001647:Bile Acids and Salts; D003524:Cyclosporins; D003404:Creatinine