VASCULAR EFFECTS OF CYCLOSPORINE-A AND ACUTE REJECTION IN CANINE HEART-TRANSPLANTATION

Background. Alteration of coronary vascular regulation during acute re jection may induce graft dysfunction and promote the occurrence of cor onary atherosclerosis in transplant recipients. We studied the effects of treated and untreated acute rejection on coronary vascular regulat ion. Methods. Two groups of mongrel dogs (n = 7) underwent heterotopic heart transplantation (cervical position) and received either no trea tment (group 1) or cyclosporin A (CyA), 10 mg.kg(-1).day(-1) (group 2) . On day 7, recipient native and transplanted hearts were harvested an d studied in organ chambers for coronary vascular reactivity. Results. Transplanted hearts from group 1 displayed grade IV histologic reject ion, whereas those from group 2 displayed grade IIIA to IV rejection. Intimal hyperplasia was found in the coronary arteries of both groups. Immunoperoxidase staining revealed the presence of factor VIII and of immunoglobulin M and G antibodies on the endothelium of both groups. Coronary relaxation to thrombin was impaired in transplanted hearts co mpared with native hearts (p < 0.05), and this was not influenced by C yA treatment. Conversely, endothelium-dependent relaxation to 5-hydrox ytryptamine was enhanced in both CyA-treated (p < 0.01) and untreated groups (p < 0.05). A facilitating effect of CyA on 5-hydroxytryptamine also was seen in transplanted hearts in group 1 versus group 2 (p < 0 .05), suggesting an intrinsic effect of CyA. Endothelium-independent r elaxation to sodium nitroprusside and the contractile response to pros taglandin F-2 alpha were not affected. Conclusions. In our model, acut e rejection did not specifically impair cyclic guanosine monophosphate -mediated relaxation, but it did affect, in a receptor-specific manner , endothelium-dependent relaxation. Cyclosporin A appeared to enhance coronary endothelial sensitivity to 5-hydroxytryptamine. (C) 1997 by T he Society of Thoracic Surgeons.