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.
Cohen
D S
DS
Department of Surgery, Division of Transplant Surgery, Medical College of Virginia, Richmond 23298-0254, USA.
Fisher
R A
RA
Tarry
W C
WC
Tawes
J W
JW
D000818:Animals; D016572:Cyclosporine / Q000008:administration & dosage / Q000633:toxicity; D004357:Drug Synergism; D006085:Graft Survival; D016027:Heart Transplantation / Q000276:immunology*; D007108:Immune Tolerance; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000633:toxicity; D008297:Male; D011090:Polyenes / Q000008:administration & dosage / Q000633:toxicity; D051381:Rats; D011912:Rats, Inbred ACI; D011917:Rats, Inbred Lew; D020123:Sirolimus; D065227:Transfusion Reaction; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D011090:Polyenes; C045571:cyclosporin G; D016572:Cyclosporine; D020123:Sirolimus