Vascular effects of cyclosporin A and acute rejection in canine heart transplantation.
BACKGROUND
Alteration of coronary vascular regulation during acute rejection may induce graft dysfunction and promote the occurrence of coronary atherosclerosis in transplant recipients. We studied the effects of treated and untreated acute rejection on coronary vascular regulation.


METHODS
Two groups of mongrel dogs (n = 7) underwent heterotopic heart transplantation (cervical position) and received either no treatment (group 1) or cyclosporin A (CyA), 10 mg.kg-1.day-1 (group 2). On day 7, recipient native and transplanted hearts were harvested and studied in organ chambers for coronary vascular reactivity.


RESULTS
Transplanted hearts from group 1 displayed grade IV histologic rejection, 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 compared with native hearts (p < 0.05), and this was not influenced by CyA treatment. Conversely, endothelium-dependent relaxation to 5-hydroxytryptamine 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 relaxation to sodium nitroprusside and the contractile response to prostaglandin F2 alpha were not affected.


CONCLUSIONS
In our model, acute 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.
Bouchard
D
D
Department of Surgery, Montreal Heart Institute, Quebec, Canada.
Despatis
M A
MA
Buluran
J
J
Cartier
R
R
D000109:Acetylcholine / Q000494:pharmacology; D000208:Acute Disease; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D003324:Coronary Artery Disease / Q000209:etiology / Q000503:physiopathology; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D016572:Cyclosporine / Q000494:pharmacology*; D015237:Dinoprost / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000737:chemistry / Q000187:drug effects / Q000503:physiopathology; D005169:Factor VIII / Q000032:analysis; D006084:Graft Rejection / Q000473:pathology* / Q000503:physiopathology; D016027:Heart Transplantation; D007124:Immunoenzyme Techniques; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009206:Myocardium / Q000473:pathology; D009599:Nitroprusside / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology; D016042:Transplantation, Heterotopic; D017539:Tunica Intima / Q000473:pathology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007166:Immunosuppressive Agents; D009599:Nitroprusside; D012701:Serotonin; D000244:Adenosine Diphosphate; D016572:Cyclosporine; D005169:Factor VIII; D015237:Dinoprost; D013917:Thrombin; D000109:Acetylcholine