Open Access Dissertation
Date of Award
Donal S. O'Leary
Muscle metaboreflex activation during dynamic exercise induces a substantial increase in cardiac work and oxygen demand via a significant increase in heart rate, ventricular contractility and afterload. This increase in cardiac work should cause coronary metabolic vasodilation. However, little if any coronary vasodilation is observed due to concomitant sympathetically induced coronary vasoconstriction. In heart failure, cardiac output does not increase with MMA presumably due to impaired left ventricular contractility, and large decreases in coronary vascular conductance are observed. The purpose of this dissertation is to determine whether the muscle metaboreflex-induced restraint of coronary vasodilation functionally limits coronary blood flow and suppresses increases in left ventricular (LV) contractility in normal dogs and whether this coronary vasoconstriction could explain in part, the reduced ability to increase cardiac performance during heart failure conditions. We used chronically instrumented dogs (n=9, control and n=7, heart failure) and measured arterial pressure (MAP), cardiac output (CO), circumflex blood flow (CBF), and calculated coronary vascular conductance (CVC), maximal derivative of ventricular pressure (dp/dt), and preload recruitable stroke work (PRSW) at rest and during mild exercise (2mph) before and during activation of the muscle metaboreflex. Experiments were repeated after systemic alpha-1 adrenergic blockade (prazosin 50-100 μg/kg). In control studies during alpha-1 blockade we observed significantly greater increases in CVC, CBF and PRSW, as well as CO and dP/dtmax, with metaboreflex activation vs. those seen without alpha-1 blockade. In heart failure experiments during MMA, the increases in CBF, CVC, CO, and +dP/dtmax were significantly greater after alpha-1 adrenergic blockade. We conclude that the coronary vasoconstriction elicited by MMA limits the ability of muscle metaboreflex to increase left ventricular contractility in normal and heart failure conditions.
Coutsos, Matthew, "Muscle Metaboreflex Control Of Coronary Blood Flow And Ventricular Contractility During Dynamic Exercise In Normal And Heart Failure Conditions" (2011). Wayne State University Dissertations. Paper 210.