[Control of the rejection process treated with cyclosporine and RS-61443, in allogeneic microsurgery transplantation of a limb, in rats].
Composite tissue allotransplantations would contribute to the reconstructions of the congenital, traumatic and tumors deformities. PURPOSE--The aim of this study is to prevent or inhibit the rejection in limb vascularized allotransplantation; decrease the toxicity of available immunosuppressive agents; determine whether combination subtherapeutic doses of CsA +RS-61443 will have an additive immunosuppressive effect. METHODS--Five groups were studied, using Brown-Norway limb donors and Fischer 344 recipient rats: group A Untreated autograft controls; group B Untreated allograft controls; group C Allografts: CsA 1.5 mg/kg/d SQ; group D Allograft: RS-61443 15 mg/kg/d; group E Allograft: combination CsA + RS-61443. RESULTS--The results were the following concerning the rejection: Group A animals displayed no rejection clinically (0%). All the skin biopsies obtained were devoid of rejection (grade 0). Group B animal developed rejection at 10-13 days post-transplantation. Skin biopsies confirmed the epidermal necrosis (grade 4). Group C animals developed rejection in 55%. Group D animals developed rejection in 94%. In contrast, Group E animals had 96% rejection-free survival up to POD 172 thus far. CONCLUSION--Combination subtherapeutic doses of CsA + RS-61443 was effective in preventing acute rejection of limb allografts and had an additive immunosuppressive effect because of the agents immunosuppressive synergistic effect.
Ferreira
L M
LM
Disciplina de Cirurgia Plástica da Escola Paulista de Medicina, São Paulo.
Anthony
J P
JP
Borsanyi
J P
JP
Benhaim
P
P
Mathes
S J
SJ
Laredo Filho
J
J
Andrews
J M
JM
D000818:Animals; D016572:Cyclosporine / Q000627:therapeutic use*; D005121:Extremities / Q000473:pathology / Q000637:transplantation*; D006084:Graft Rejection / Q000517:prevention & control*; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008866:Microsurgery; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D014181:Transplantation Immunology
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid