Muscle metaboreflex stimulates the cardiac sympathetic afferent reflex causing positive feedback amplification of sympathetic activity: effect of heart failure

Abstract

Exercise intolerance is a hallmark symptom of heart failure and to a large extent stems from reductions in cardiac output that occur due to the inherent ventricular dysfunction coupled with enhanced muscle metaboreflex-induced functional coronary vasoconstriction which limits increases in coronary blood flow. This creates a further mismatch between O2 delivery and O2 demand which may activate the Cardiac Sympathetic Afferent Reflex (CSAR) causing amplification of the already increased sympathetic activity in a positive-feedback fashion. We utilized our chronically instrumented conscious canine model to evaluate if chronic ablation of afferents responsible for the CSAR would attenuate the gain of muscle metaboreflex before and after induction of heart failure. After afferent ablation, the gain of the muscle metaboreflex control of mean arterial pressure was significantly reduced before (-239.5 ± 16 to -95.2 ± 8 mmHg/l/min) and after the induction of heart failure (-185.6 ± 14 to -95.7 ± 12 mmHg/l/min). Similar results were observed for the strength (gain) of muscle metaboreflex control of heart rate, cardiac output, and ventricular contractility. Thus, we conclude that the CSAR contributes significantly to the strength of the muscle metaboreflex in normal and heart failure animals serving as an effective positive-feedback amplifier thereby further increasing sympathetic activity.