Clinical heart failure is characteristic by neurohormonal activation including activation of the sympathetic nervous system. This heightened sympathoexcitation is thought to play an important role in the pathophysiology of the heart failure syndrome. Abnormalities of baroreflex circulatory control have also been noted with symptomatic heart failure and are felt to play an important role in the sympathetic neural activation in these patients. There is recent evidence for increased levels of neurohormones in patients with asymptomatic left ventricular dysfunction. Experimental studies have demonstrated that baroreflex abnormalities occur very early in the course of heart failure in animal models. We propose to study the reflex control of the circulation in patients with left ventricular dysfunction without symptoms of heart failure to further understanding of the role that these reflex abnormalities play in the pathogenesis of the heart failure syndrome. Specifically, this proposal is directed at elucidating the mechanism(s) responsible for abnormal sympathetic circulatory control in human heart failure and the potential for therapeutic modalities to influence these mechanisms. The studies outlined will consist of: 1) microneurographic studies and assessment of reflex control in patients with asymptomatic left ventricular dysfunction (first year of research), 2) study of effects of opioid receptor blockade with naloxone on sympathetic neural regulation in heart failure patients (second year of research), and 3) the effects of heart failure on reflex control of renal circulation in humans (first and second years of protocol).
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