My current position is an Assistant Professor of Physiology at Wayne State University School of Medicine. I have been allocated sufficient laboratory space and substantial start up funds to furnish my laboratory with state of the art instrumentation necessary to function as an independent investigator. My immediate goals are to develop an independent research program studying the reflex control of the cardiovascular system. My long term goals are to remain in academia and to become a successful senior investigator and educator. I feel an RCDA will greatly enhance the probabilities of achieving these goals. The research I have chosen to address, studies in conscious, chronically instrumented dogs, requires substantial time and effort. At this pivotal stage in my career the ability to devote the significant extra time to research which gaining an RCDA would provide, would substantially speed and improve my development as an independent researcher. My research plan focuses on two powerful reflexes capable of mediating the cardiovascular adjustments to dynamic exercise; the muscle chemoreflex and the arterial baroreflex. The functional importance of each of these reflexes during dynamic exercise is unclear. Situations exist when these reflexes may be combating each other or when these reflexes may induce cardiovascular responses in the same direction. For example, in patients with peripheral vascular disease, blood flow to the active muscle may be restricted inducing muscle chemoreflex mediated increases in arterial pressure. In this setting, the arterial baroreflex would oppose any rise in blood pressure. Alternatively, in patients with cardiac limitations, the exaggerated peripheral vasoconstriction and tachycardia observed during dynamic exercise may stem from activation of the muscle chemoreflex (due to underperfused active skeletal muscle) or via activation of the arterial baroreflex (due to a lower than normal arterial pressure) or both. Using two well developed animal models; the conscious dog chronically instrumented to control blood flow to the hindlimb skeletal muscles, and the conscious dog with atrioventricular block in which cardiac output can be controlled on a beat-by-beat basis; this proposal is focused on determining the functional importance of the muscle chemoreflex and arterial baroreflex during dynamic exercise. The experiments are designed to activate the muscle chemoreflex and the arterial baroreflex in opposition and concurrently in order to determine the strengths (gains) of each reflex, the efferent mechanisms of action of each reflex, and the extent of interaction between reflexes. A key hypothesis addressed is that the functional importance of each reflex during dynamic exercise is intimately dependent on both the level of cardiac output and the level of dynamic exercise. These studies will provide a firm, quantitative, and mechanistic basis for our understanding of the reflex control of the cardiovascular system during dynamic exercise.
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