Selective lymphoid irradiation and cyclosporin A in rat heart allografts.
Short-term peritransplant treatment utilizing 2-dose ALG and 1-dose Palladium-109-hematoporphyrin (PD-H) for selective lymphoid irradiation (SLI) leads to donor-specific permanent acceptance of heart allografts in the Fisher to Lewis rat model. The same treatment significantly prolongs survival of hearts transplanted to strongly histoincompatable , presensitized, and xenogeneic recipients. The purpose of this study was to evaluate synergistic effects of short-term, low-dose cyclosporin treatment and SLI in an attempt to develop a nontoxic protocol utilizing peritransplant treatment for immune preconditioning with minimal subsequent immunosuppression. Single-agent treatment alone with cyclosporin, ALG, or Pd-H resulted in a maximal mean graft survival time (MST) of 33 days. Immunosuppression with 1-dose Pd-H, 2-dose ALG, and low-dose cyclosporin (5 mg/kg) for 14 days doubled the MST to 78 days. Use of therapeutic-dose cyclosporin (20 mg/kg), given for just 3 days, was also quite effective, MST of 57 days with SLI and 43 days with ALG, but toxic; 3 of 12 recipients died of infection with functioning grafts. These results demonstrate that the use of low-dose cyclosporin over a short interval, when combined with peritransplant SLI, is a highly effective and safe method for prolonging heart allograft survival.
D000818:Animals; D003131:Combined Modality Therapy; D003524:Cyclosporins / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D006082:Graft Enhancement, Immunologic; D006085:Graft Survival; D016027:Heart Transplantation; D008221:Lymphoid Tissue / Q000528:radiation effects*; D008665:Metalloporphyrins / Q000627:therapeutic use*; D010165:Palladium / Q000627:therapeutic use*; D011868:Radioisotopes / Q000627:therapeutic use*; D051381:Rats; D011912:Rats, Inbred ACI; D011917:Rats, Inbred Lew
D003524:Cyclosporins; D008665:Metalloporphyrins; D011868:Radioisotopes; C041377:palladium hematoporphyrin; D010165:Palladium