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 often profound activation of the sympathetic nervous system 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 inasmuch as the increase in muscle blood flow during exercise is significantly reduced form normal levels. The mechanisms mediating these responses are poorly understood. Two powerful reflexes exist which are capable of inducing the altered cardiovascular responses in subjects with heart failure: the muscle metaboreflex and the arterial baroreflex. The purpose of the present proposal is to determine the relative roles of these powerful cardiovascular reflexes in mediating the reflex responses to dynamic exercise in an experimental model of heart failure. During dynamic exercise in heart failure subjects muscle blood flow may be compromised thus, the muscle metaboreflex may, in part, mediate the reflex changes in arterial pressure, heart rate, and systemic vascular conductance in order to minimize any error in blood flow to the active skeletal muscle. Alternatively, strong evidence indicates that the arterial baroreflex is 'reset' during dynamic exercise such that the operating point of the baroreflex is shifted to a higher pressure. Since in heart failure the ability to increase cardiac output during exercise is compromised, the altered cardiovascular adjustments during dynamic exercise in heart failure may stem from arterial baroreflex corrections of a mismatch between cardiac output and total vascular conductance. Such a mismatch would displace arterial pressure from the reset baroreflex operating point thus eliciting baroreflex induced sympathetic activation. Thus, this proposal is focused on quantifying the relative importance of the muscle metaboreflex and the arterial baroreflex in mediating the altered cardiovascular responses to dynamic exercise in heart failure.
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