Integrative Aspects of Cardiovascular Function

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DESCRIPTION (Applicant's abstract): The overall goal of this project is to further our understanding of the mechanisms that evoke the hemodynamic adjustments that accompany dynamic exercise. These studies will investigate how, and when, mechanical (hydraulic) factors, local regulatory mechanisms, and reflex control mechanisms promote or impede these adjustments. All studies are to be carried out in conscious, chronically prepared animals at rest and during voluntary treadmill exercise. A fundamental gap in our understanding of the regulation of muscle blood flow during exercise stems from our inability to identify how much of the rise in blood flow in exercise is attributable to the muscle pump versus metabolic vasodilation. Aims 1 to 3 seek to fill this void by quantifying the interaction between metabolic vasodilation and muscle pumping during alterations in the mechanical factors (speed and grade) by which a given amount of treadmill work is achieved. The approach will be to eliminate vasodilation thereby revealing the effects of the muscle pump in isolation. Other goals include determining how tightly coupled muscle blood flow is to the mechanical activity of muscle (muscle pumping) during locomotion and to determine when the blood flow-raising effect of the muscle pump "wears-off' following a muscle contraction. In Aim 4, the role of the venous system in making blood available to the heart will be examined by determining the effect on cardiac filling pressure of actively changing the distribution of cardiac output between compliant and non-compliant circulations. The approach is to control and manipulate cardiac output and hindlimb blood flow (a non-compliant circulation) by computer controlled ventricular pacing and vascular occluder cuffs. Aim 5 seeks to determine when, if ever muscle chemoreflexes play an important role in voluntary locomotory exercise. The final Aim 6 will determine the influence of exercise, and specifically of muscle chemoreflexes, on arterial baroreflex stimulus-response curves to see if exercise and/or muscle chemoreflexes "reset" the baroreflex to a higher operating point in exercise. The knowledge gained from these aims will further our understanding of the basic physiology of how the cardiovascular system functions as well as the hemodynamic consequences of heart failure, peripheral vascular abnormalities, and other states.