Cyclosporin A in orthotopic canine hepatic transplants

Abstract

Cyclosporin A, a potent yet selective immunosuppressant, does not appear to predispose to the infectious and metabolic complications seen with conventional immunosuppression. The purpose of this work is to determine the efficacy and dose requirements of Cyclosporin A in canine orthotopic hepatic transplantation and to assess potential toxicity in the hepatic allograft. Twenty dogs received orthotopic hepatic transplantation and survived 5 or more days postoperatively. Nine dogs received azathioprine 4–6 mg/kg, nine Cyclosporin A, 20 mg/kg incrementally decreased by 50% at 14 day intervals, and two dogs received no immunosuppression. Serial determinations of serum bilirubin, alkaline phophatase, WBC, Hgb, Hct, and serial percutaneous liver biopsies were performed. Average survival for the control dogs (no immunosuppression) was 11 days, the azathioprine group, 16.9 days, and the Cyclosporin A dogs, 37.7 days ( P < 0.05). Liver function studies at 7, 14, and 21 days were remarkably preserved in the Cyclosporin A-treated group compared to the controls and azathioprine group. No histologic or biochemical evidence of rejection appeared until the daily dose of Cyclosporin A fell below 20 mg/kg. No histologic or biochemical evidence of renal or hepatic toxicity was evident in the Cyclosporin A-treated dogs. Cyclosporin A at 20 mg/kg was found to be efficacious in canine hepatic transplants with significantly improved survival and liver function compared to azathioprine.