Objective. The longterm goal of this project is to investigate further the role of the sympathetic nervous system in determining sudden cardiovascular death during ventricular tachycardia in humans, and thereby improve survival. Background. In humans, sympathetic nerve activation during ventricular tachycardia is an important determinant of hemodynamic stability during ventricular tachycardia, independent of ventricular function and tachycardia rate. In animal models, the arterial baroreflex and cardiopulmonary baroreflex have important, yet opposing, effects on sympathetic activation during ventricular tachycardia. The relative contributions of these control mechanisms in humans is unknown.
Specific Aims. The immediate aim o this study is to determine the roles of the arterial and cardiopulmonary baroreflexes, and the additional contributions of ventricular dysfunction and orthostatic stress, in determining sympathetic activation and hemodynamic stability during ventricular tachycardia in humans. Design. Using microneurography of the peroneal nerve, sympathetic nerve activity directed to muscle and to skin will be measured and compared in patients with hemodynamically stable and unstable ventricular tachycardia. A series of interventions which selectively activate arterial and cardiopulmonary baroreceptors will be performed to determine the contribution of each to sympathetic responses observed during induced ventricular tachycardia or rapid ventricular pacing. Patients with a wide range of ventricular function will be studied, including those with advanced heart failure and patients who have undergone orthotopic heart transplant (which denervates cardiopulmonary baroreceptors). Chaos theory will be used to analyze sympathetic recordings in the different patient groups, based on preliminary results suggesting qualitative differences between normal subjects and heart failure patients. Significance. The knowledge gained from these studies may serve as a basis for the development of medical and surgical therapies directed at the correction of the underlying abnormalities that predispose the patient to hemodynamically unstable ventricular tachycardia degenerating into ventricular fibrillation and sudden cardiovascular death.
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