Cyclosporin A and transplant coronary disease after heart transplantation: facts and fiction.
From published data in the currently available literature on animal experiments, it can be concluded that CyA may be involved in the development of hypertension and renal dysfunction. These side effects are probably related to a disturbed vasomotor tone and a pathologic reaction to physiologic vasoconstrictive and vasodilative agents following administration of high doses of CyA. These effects are dose related and reversible and were undetected at clinically applied levels of immunosuppression. It therefore appears to be unlikely that this pathologic response is operative in precipitating or promoting TCD, which is supported by findings of in vivo and in vitro studies on human coronary arteries as well as by comparison of immunosuppressive protocols comparing series with and without application of CyA. Chronic graft dysfunction, as depicted by late mortality in heart and isolated lung transplant recipients and by loss of kidney allograft survival, yields an annual rate of between 4 and 6% per year. It is only in heart transplantation that TCD has been tried to be associated with CyA application. If CyA-related damage were to occur in coronary arteries independent from immunologic factors, the incidence of coronary disease should be similar in heart, lung, liver, and kidney transplants. This is not the case. Although continuous investigation on the side effects of immunosuppressive agents is definitely necessary, we should concentrate our research activities on potential prophylactic and therapeutic measures to overcome the single most important risk factor of long-term surviving patients after solid organ transplantation: chronic rejection.
Haverich
A
A
Department of Cardiovascular Surgery, University of Kiel, Germany.
Costard-Jäckle
A
A
Cremer
J
J
Herrmann
G
G
Simon
R
R
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D003327:Coronary Disease / Q000139:chemically induced / Q000453:epidemiology* / Q000401:mortality; D003331:Coronary Vessels / Q000187:drug effects; D016572:Cyclosporine / Q000009:adverse effects* / Q000494:pharmacology; D004195:Disease Models, Animal; D005500:Follow-Up Studies; D016027:Heart Transplantation / Q000276:immunology* / Q000401:mortality; D006801:Humans; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D005996:Nitroglycerin / Q000494:pharmacology; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors
D016572:Cyclosporine; D005996:Nitroglycerin