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Date of Award
Donal S. O'Leary
Stimulation of skeletal muscle afferents by metabolites that accumulate in the exercising muscle elicits a large pressor response, termed the muscle metaboreflex. Muscle metaboreflex activation during submaximal exercise induces large increases in arterial pressure, cardiac output, heart rate and ventricular contractility however, the vascular responses have varied in previous studies. We addressed three specific questions: 1) what are the mechanism(s) regulating the non-ischemic vasculature during muscle metaboreflex activation in normal subjects, 2) whether muscle metaboreflex activation vasoconstricts the ischemic active muscle from which this reflex originates and if this vasoconstriction is exaggerated in heart failure and 3) how do the arterial baroreflex and muscle metaboreflex interact with each other when activated simultaneously in normal and heart failure animals. Using chronically instrumented canine model, data was collected before and after the induction of heart failure. We found that: 1) muscle metaboreflex activation induces epinephrine release causing β2-mediated vasodilation in skeletal muscle, 2) muscle metaboreflex activation elicits vasoconstriction of ischemic active muscle which is exaggerated after induction of heart failure and 3) interaction between baroreflex and muscle metaboreflex in normal animals depends on the parameter being investigated however in heart failure, most cardiovascular variables exhibit occlusive interaction. Preferential vasoconstriction of non-ischemic vasculature redirects cardiac output and increases hindlimb blood flow in normal animals but this increase is significantly attenuated in heart failure. The exaggerated vasoconstriction and limited increase in blood flow to the ischemic muscle would impair the ability to exercise and contribute to exercise intolerance in heart failure patients.
Kaur, Jasdeep, "Muscle Metaboreflex And Arterial Baroreflex: Action, Interaction And Altered Control In Heart Failure" (2016). Wayne State University Dissertations. 1453.