The hypothesis underlying the present proposal is that physiologic hypertrophy of the myocardium protects against and possibly reverses the myocardial deterioration associated with pathologic hypertrophy. To explore this hypothesis, several experimental models of hypertrophy will be characterized in the rat. These will include systolic overload (secondary to abdominal or ascending aortic banding), diastolic overload (secondary to arterio-venous fistula formation), chronic beta-adrenergic stimulation (using chronic sub-cutaneous dobutamine infusion), and physical training. The resultant hypertrophy will be characterized physiologically, using an isolated working heart preparation, and biochemically as regards myosin isozyme content and ATPase activity and as to adrenergic receptor number and affinity. It will then be possible to superimpose physiologic stimuli on pathologically loaded hearts to investigate the mechanical and biochemical characteristics of the resultant hypertrophy. Since ventricular function is a prime determinant of prognosis in a wide variety of clinical conditions, a basic understanding of the mechanisms by which the heart responds to pathologic overload states and an approach to preventing and perhaps reversing the associated ventricular dysfunction is of great importance.
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