[Experimental study of the effectiveness of immunosuppression therapy using FK506 and 15-deoxyspergualin in concordant xenotransplantation].
The effect of combination therapy with FK506 (FK) and 15-deoxyspergualin (DSG) was investigated in a concordant xenotransplantation model in which hamster hearts were implanted into LEW rats. Forty xenograft procedures were carried out in this study. Recipients were divided into eight groups. Control Group received no therapy. Group A, B, and C were administered different dosages of FK; 0.75, 1.0 and 1.25 (mg/kg/day), respectively. In Group D and E, DSG at 10 and 20 mg/kg/day was administered after the transplantation. In Group F and G received combined administration of FK and DSG (Group F; FK 0.5 + DSG 10, Group G; FK 0.5 + DSG 5). Recipients were injected with immunosuppressive agent intraperitoneally from day 0 until cessation of heart beat. At the time of grafting, splenectomy was performed in all groups. FK treatment of the recipients did not lead to significant improvement in graft survival, 7.2 +/- 0.8 and 6.3 +/- 0.7 days, compared with 3.5 +/- 1.23 days in Control. DSG groups showed xenograft survival of 11.5 +/- 0.9 and 8.1 +/- 1.6 days, respectively. The combined therapy prolonged graft survival to 33.67 +/- 11.37 days in Group F, and to 47.3 +/- 11.02 days in Group G. Combined therapy produced complete suppression of antibody formation, but in FK 0.5 + DSG 10 mg/kg/ day treated group, there was abrupt elevation of anti-hamster antibody titer at the time of rejection. Only in combined therapy groups did recipients obtain long-term graft survival, but recipients receiving treatment with FK 0.5 + DSG 10 (mg/kg/day) suffered from severe emaciation, losing nearly 31% of their body weight. However, animals that received a low dose of DSG in combined therapy groups did not lose body weight over 8 weeks. Combination therapy with FK and DSG was shown to prolong graft survival time effectively, and FK 0.5 + DSG 5 (mg/kg/day) was an appropriate dose in xenotransplantation with minimal side effects.
Maeda
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Department of Cardiovascular Surgery, Heart Institute of Japan, Tokyo Women's Medical College, Tokyo, Japan.
D000818:Animals; D006224:Cricetinae; D004359:Drug Therapy, Combination; D006085:Graft Survival / Q000187:drug effects; D006146:Guanidines / Q000008:administration & dosage*; D016027:Heart Transplantation; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008647:Mesocricetus; D051381:Rats; D011917:Rats, Inbred Lew; D016559:Tacrolimus / Q000008:administration & dosage*; D014183:Transplantation, Heterologous; D016042:Transplantation, Heterotopic
D006146:Guanidines; D007166:Immunosuppressive Agents; C037258:gusperimus; D016559:Tacrolimus