The broad objective of the proposed study is to determine the role of sympathetic activity and hemodynamic load on cardiac muscle performance, mass and contractile proteins. The rat heterotopic cardiac isograft is perfused by the same hormonal milieu as the native heart but hemodynamic load on the myocardium is reduced thereby allowing a careful study of the unloaded, denervated heart exposed to various external stimuli. Initial studies of the acute and chronic hemodynamic characteristics and coronary blood flow in the isograft will facilitate interpretation of subsequent experiments. In the isograft, myocardial catecholamines and myosin isoenzymes will be correlated with isolated papillary muscle mechanics from animals conditioned by chronic running or swimming to determine the degree to which the transplanted heart responds to circulating catecholamines. The role of heart rate on protein synthesis and mRNA of the isograft will be examined at several time points following transplantation. Heart rate of the isograft will be increased by external pacing at rates greater than the intrinsic heart rate. Myocardial infarction results in cell loss and compensation by the surviving tissue. Ventricular remodeling presumably occurs in response to an increased pressure load. Coronary ligation in the isograft will provide information on how the heart responds to a reduced hemodynamic load following segmental tissue loss.
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