Cyclic adenosine monophosphate content of endomyocardial tissue obtained by biopsy in cyclosporine immunosuppressed human cardiac transplant recipients

Abstract

Our laboratory has previously reported the myocardial cyclic adenosine monophosphate (AMP) content in normal humans and patients with cardiomyopathy. 1 Concentric left ventricular hypertrophy and hemodynamic abnormalities suggestive of diastolic dysfunction have been observed in the transplanted heart. 2,3 The etiology of the diastolic dysfunction is unknown. Cyclic AMP content may increase in response to depletion of myocardial energy stores and may serve as a stimulus for protein synthesis and ventricular hypertrophy. Cyclosporine, a commonly used immunosuppressive agent, has been shown to have an affinity for the calcium regulatory protein calmodulin. 4 Calmodulin in vitro can stimulate adenylate cyclase, thereby potentially increasing cyclic AMP, and, in addition, can stimulate phosphodiesterase, hence theoretically decreasing cyclic AMP levels. This investigation measures the myocardial cyclic AMP content in cyclosporine-treated cardiac transplant recipients. We hypothesized that the hemodynamic and anatomic (hypertrophy) abnormalities observed in the transplanted heart may be related to abnormalities in myocardial cyclic AMP content.