A hallmark feature of ventricular dysfunction is decreased exercise tolerance. Even in normal subjects, dynamic exercise presents one of the greatest challenges to cardiovascular control. During strenuous dynamic exercise with a large muscle mass, cardiac output increases and vascular conductance to inactive areas decreases in order to provide both sufficient blood flow to active skeletal muscle and to maintain arterial blood pressure. In subjects with heart failure, these problems become exacerbated due to the limitations in ventricular function resulting in markedly altered cardiovascular responses to dynamic exercise. In this setting profound activation of the sympathetic nervous system often occurs as evidenced by high plasma catecholamines and intense vasoconstriction in inactive areas such as the splanchnic and renal vasculatures. Even active skeletal muscle may be relatively vasoconstricted. The mechanisms mediating these responses are poorly understood. 2 powerful reflexes exist which are capable of inducing the altered cardiovascular responses in subjects with heart failure: the muscle metaboreflex and the arterial baroreflex. Experiments described in this proposal are designed to test the functional importance of the muscle metaboreflex and the arterial baroreflex in mediating the altered cardiovascular responses to exercise in heart failure. Using our powerful conscious, chronically instrumented animal model, these studies are focused on determining the mechanisms of mediating these reflexes, the extent of interaction between these reflexes and how these mechanisms and interactions are altered in heart failure. Furthermore, we will explore the relationships between coronary blood flow and ventricular function during exercise in heart failure and whether recovery of normal cardiovascular control mechanisms can occur with the recovery from heart failure.
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