Effects of cyclosporin, FK506, and rapamycin on graft-vessel disease.
Graft-vessel disease (GVD) limits the long-term survival of heart-transplant patients, and this effect has not been altered by use of cyclosporin for immunosuppression. We compared the effects of the immunosuppressants cyclosporin, FK506, and rapamycin on GVD in a rat-heart transplantation model. Allografted hearts from rats treated with 1 mg/kg FK506 for 50 days showed the same degree of myocardial rejection but a significantly worse (p less than 0.05) grade of GVD compared with grafted hearts from rats treated with 1.5 mg/kg cyclosporin for the same time. 2 mg/kg FK506 for 50 days prevented cellular rejection but GVD was as severe as that found with 1 mg/kg FK506. Moderate GVD was present in two of five allografted hearts after treatment with 4 mg/kg FK506. 1.5 mg/kg rapamycin for 50 days was an effective inhibitor of rejection and GVD. Based on our results in rats, the possibility that GVD may occur in human heart-transplant recipients treated with FK506 cannot be excluded.
Meiser
B M
BM
Department of Cardiothoracic Surgery, Stanford University School of Medicine, California.
Billingham
M E
ME
Morris
R E
RE
D000818:Animals; D003524:Cyclosporins / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000187:drug effects; D006086:Graft vs Host Disease / Q000473:pathology / Q000517:prevention & control*; D016027:Heart Transplantation; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D011090:Polyenes / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D020123:Sirolimus; D016559:Tacrolimus / Q000627:therapeutic use*; D013997:Time Factors
D003524:Cyclosporins; D007166:Immunosuppressive Agents; D011090:Polyenes; D020123:Sirolimus; D016559:Tacrolimus