MECHANISMS OF HEART FAILURE

These studies are aimed at defining the nature and cause of the hereditary cardiomyopathy that develops in the Syrian hamster. This animal model of heart failure is unique and should help to shed light on the pathophysiology of myocardial failure in man. Integrated and collaborative studies are being pursuet which should help to define the basic nature of the process. Structural studies are proceeding to define alterations in small vessels which may explain the myolysis in the loss of cells which results in early scarring of the myocardium. Vascular spasm has been demonstrated in this model and alterations of the vascular spasm have been produced pharmacologically. Whether or not these are causal is subject to current study. A single cell preparation of the adult myopathic myocardium has been developed which will help to overcome the problem of heterogeneity of the overall heart. Contractile, electrical and structural properties of these single cells are currently being defined. Contractile protein alterations are being studied relative to time. We have shown that these occur as a reaction to the process and are not an initial event. Characterization of neutral proteases which remove specific parts of the myosin molecule have also been characterized and are being further related to the myopathic process. Studies of synthetic mechanism and nuclear histones are in process. Abnormalities in the synthetic mechanisms have been defined and are being further characterized. The neuro-humeral alterations that occur in heart failure have also been delineated in this model including alterations in the catecholamines as well as in the metabolism of serotonin. These studies are being pursued in a closely collaborative mode and have been highly productive as to the initial etiology of the disease and its ultimate cause.