Cardiac allograft tolerance induction with limited immunosuppression

We evaluated the efficacy and systemic toxicity of cyclosporine G, rapamycin, and cyclosporine A with multiple donor-specific blood transfusions in the stringent ACI to Lewis heterotopic cardiac transplant model. In addition, all animals received a 28-day post-operative course of cyclosporine A. Systemic toxicity was assessed by measuring recipient body weight at 30 and 60 days posttransplantation and at the time of graft rejection. Preengraftment cyclosporine G (10 mg/kg) resulted in a mean graft survival of 7.31 +/- 1.09 days (n=13; N.S. vs Control). A 10-day course of the novel immunosuppressant rapamycin (d4-14) combined with our standard 28-day cyclosporine A protocol resulted in a mean graft survival of 206.0 +/- 143.6 days (n=5; P < 0.05 vs Control). Furthermore, the rapamycin injection vehicle was found to have no intrinsic immunosuppressive activity or systemic toxicity. The addition of pre- (d-1) and post- (d7, 14, 21) engraftment donor-specific transfusion resulted in a mean allograft survival of 131.2 +/- 43.9 days. No significant difference in interval weight was observed in any of the experimental groups. We conclude that cyclosporine G is of little value in this experimental model. However, rapamycin combined with cyclosporine A provides effective immunosuppressive synergy without significant toxicity or the sensitization risk inherent in donor-specific blood transfusions.