Chronic elevations in plasma arterial catecholamines are associated with many cardiovascular disease states including heart failure and mitral valve prolapse. Furthermore, these patients often have ischemic heart disease, myocardial dysfunction, trasient hypertension and exercise intolerance. The goal of our studies is to define the changes and mechanisms responsible for alterations in myocardial function, the maintenance of arterial pressure, myocardial hypertrophy and morphometric/ultrastructural changes in the right and left ventricle during prolonged (greater than 28 days) elevations (2000- 4000 pg/ml) in plasma arterial norepinephrine. These goals will be accomplished by instrumenting dogs using general surgical procedure, then allowing them to fully recover. Animals will be studied in the conscious state and then miniosmotic pumps implanted which release norepinephrine for 28 days. Pumps will be reimplanted and studied again during chronic elevations in plasma norepinephrine at 25 day intervals. During this investigatorship we will study the control of myocardial function, the reflex regulation of pressure, myocardial size and cellular alterations in the myocardium. Using morphometric techniques with light and electron microscopy we will attempt to define for the first time in a uniform population of beagle dogs of similar size, age and sex, the microvascular changes and the ultrastructural basis of the hypertrophy which occurs during chronic infusion of norepinephrine. Besides the physiologic and ultrastructural basis of the hypertrophy, we will define the role of the systemic arterial baroreflexes in the maintenance of pressure in dogs with high circulating norepinephrine. The mechanisms of baroreflex regulation under these conditions will be a major focus of these studies.
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