The specific aims of the proposed research are to: 1) investigate reflex cardiovascular control in humans by studying patients before and following cardiac transplantation. These patients will be in congestive heart failure preoperatively and will have cardiac (mainly ventricular) denervation and normal cardiac function postoperatively. The effects of heart failure and of ventricular deafferentation on the reflex control of the circulation will be assessed in these patients. The role of vestibulocerebellar mechanisms in the reflex control of circulation will be assessed in normal subjects. The techniques of investigation to be used include alterations in cardiopulmonary baroreceptor input with lower body negative pressure and leg elevation, alterations in carotid baroreceptor input with a neck chamber, activation of somatic reflexes by isometric handgrip, and alteration in baroreceptor input with vasoactive drugs. Changes in heart rate (or PP interval of recipient heart) and forearm and peripheral vascular resistances will be assessed. 2) Determine the effect of chronic myocardial infarction in dogs on arterial and cardiopulmonary baroreflexes. Responses of heart rate and sympathetic nerve traffic to alterations in baroreceptor and cardiopulmonary receptor input will be determined before and following induction of a myocardial infarction. These experiments will provide insight into the neural control of the circulation after myocardial infarction. 3) Assess the influence of intracerebroventricular administration of angiotensin II and vasopressin on arterial and cardiopulmonary baroreflex control of heart rate and sympathetic outflow in conscious rabbits. Many peptides may act centrally to alter blood pressure and heart rate but little is known about their influence on reflex control of sympathetic outflow to the periphery. 4) Continue to assess the behavior of cardiac receptors in hypertension and heart failure and to determine the influence of hypertension and heart failure on reflex control of sympathetic outflow to selected vascular beds. These experiments (both afferent recordings and reflex studies) will be performed in rabbits. Hypertension will be reduced by wrapping the left kidney in cellophane and removing the right kidney. Heart failure will be induced by suprarenal aortic constriction. The pursuit of these specific aims is likely to provide important mechanistic information which will permit the design of new therapeutic strategies for treatment of patients with heart failure, hypertension and chronic myocardial infarction.
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