CARDIAC ALLOGRAFT TOLERANCE INDUCTION WITH LIMITED IMMUNOSUPPRESSION

We evaluated the efficacy and systemic toxicity of cyclosporine G, rap amycin, and cyclosporine A with multiple donor-specific blood transfus ions in the stringent ACI to Lewis heterotopic cardiac transplant mode l. In addition, all animals received a 28-day postoperative course of cyclosporine A. Systemic toxicity was assessed by measuring recipient body weight at 30 and 60 days posttransplantation and at the time of g raft 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) combi ned with our standard 28-day cyclosporine A protocol resulted in a mea n 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 int rinsic immunosuppressive activity or systemic toxicity. The addition o f pre- (d-1) and post- (d7, 14, 21) engraftment donor-specific transfu sion resulted in a mean allograft survival of 131.2 +/- 43.9 days. No significant difference in interval weight was observed in any of the e xperimental groups. We conclude that cyclosporine G is of little value in this experimental model. However, rapamycin combined with cyclospo rine A provides effective immunosuppressive synergy without significan t toxicity or the sensitization risk inherent in donor-specific blood transfusions. (C) 1996 Academic Press, Inc.