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The ability to increase cardiac output during dynamic exercise is paramount for the ability to maintain workload performance. Reflex control of the cardiovascular system during exercise is complex and multifaceted involving multiple feedforward and feedback systems. One major reflex thought to mediate the autonomic adjustments to exercise is termed the muscle metaboreflex and is activated via afferent neurons within active skeletal muscle which respond to the accumulation of interstitial metabolites during exercise when blood flow and O2 delivery are insufficient to meet metabolic demands. This is one of the most powerful cardiovascular reflexes capable of eliciting profound increases in sympathetic nerve activity, arterial blood pressure, central blood volume mobilization, heart rate and cardiac output. This review summarizes the mechanisms meditating muscle metaboreflex‐induced increases in cardiac output. Although much has been learned from studies using anaesthetized and/or decerebrate animals, we focus on studies in conscious animals and humans performing volitional exercise. We discuss the separate and interrelated roles of heart rate, ventricular contractility, ventricular preload and ventricular–vascular coupling as well as the interaction with other cardiovascular reflexes which modify muscle metaboreflex control of cardiac output. We discuss how these mechanisms may be altered in subjects with heart failure with reduced ejection fraction and offer suggestions for future studies. [ABSTRACT FROM AUTHOR]

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 used 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 animals with heart failure serving as an effective positive-feedback amplifier thereby further increasing sympathetic activity. [ABSTRACT FROM AUTHOR]

Slow heart rate recovery following exercise may be influenced by persistent sympathoexcitation. This study examined 1) the effect of muscle metaboreflex activation (MMA) on heart rate recovery following dynamic exercise; and 2) whether the effect of MMA on heart rate recovery is reversible by reducing sympathoexcitation [baroreflex activation via phenylephrine (PE)] in canines. Twenty-two young adults completed control and MMA protocols during cycle ergometry at 110% ventilatory threshold with 5 min recovery. Heart rate recovery kinetics [tau (s), amplitude, end-exercise, and end-recovery heart rate] and root mean square of successive differences (RMSSD) were measured. Five chronically instrumented canines completed control, MMA (50%-60% imposed reduction in hindlimb blood flow), and MMA with end-exercise PE infusion (MMA þ PE) protocols during moderate exercise (6.4 km·h-1) and 3 min recovery. Heart rate recovery kinetics and MAP were measured. MAP increased during MMA versus control in canines (P < 0.001). Heart rate recovery s was slower during MMA versus control in humans (17% slower; P = 0.011) and canines (150% slower; P = 0.002). Heart rate recovery s was faster during MMA þ PE versus MMA (40% faster; P = 0.034) and was similar to control in canines (P = 0.426). Amplitude, end-exercise, and end-recovery heart rate were similar between conditions in humans (all P = 0.122) and in canines (all P ≥ 0.084). MMA decreased RMSSD in early recovery (P = 0.004). MMAinduced sympathoexcitation slows heart rate recovery and this effect is markedly attenuated with PE. Therefore, elevated sympathoexcitation via MMA impairs heart rate recovery and inhibition of this stimulus normalizes, in part, heart rate recovery. [ABSTRACT FROM AUTHOR]

Blood flow restriction training (BFRT) employs partial vascular occlusion of exercising muscle and has been shown to increase muscle performance while using reduced workload and training time. Numerous studies have demonstrated that BFRT increases muscle hypertrophy, mitochondrial function, and beneficial vascular adaptations. However, changes in cardiovascular hemodynamics during the exercise protocol remain unknown, as most studies measured blood pressure before the onset and after the cessation of exercise. With reduced perfusion to the exercising muscle during BFRT, the resultant accumulation of metabolites within the ischemic muscle could potentially trigger a large reflex increase in blood pressure, termed the muscle metaboreflex. At low workloads, this pressor response occurs primarily via increases in cardiac output. However, when increases in cardiac output are limited (e.g., heart failure or during severe exercise), the reflex shifts to peripheral vasoconstriction as the primary mechanism to increase blood pressure, potentially increasing the risk of a cardiovascular event. Using our chronically instrumented conscious canine model, we utilized a 60% reduction in femoral blood pressure applied to the hindlimbs during steadystate treadmill exercise (3.2 km/h) to reproduce the ischemic environment observed during BFRT. We observed significant increases in heart rate ( þ 19 ± 3 beats/min), stroke volume ( þ 2.52 ± 1.2 mL), cardiac output ( þ 1.21 ± 0.2 L/min), mean arterial pressure ( þ 18.2 ± 2.4 mmHg), stroke work ( þ 1.93 ± 0.2 L/mmHg), and nonischemic vascular conductance ( þ 3.62 ± 1.7 mL/mmHg), indicating activation of the muscle metaboreflex. NEW & NOTEWORTHY Blood flow restriction training (BFRT) increases muscle mass, strength, and endurance. There has been minimal consideration of the reflex cardiovascular responses that could be elicited during BFRT sessions. We showed that during low-intensity exercise BFRT may trigger large reflex increases in blood pressure and sympathetic activity due to muscle metaboreflex activation. Thus, we urge caution when employing BFRT, especially in patients in whom exaggerated cardiovascular responses may occur that could cause sudden, adverse cardiovascular events. [ABSTRACT FROM AUTHOR]

Rapid regulation of arterial blood pressure on a beat-by-beat basis occurs primarily via arterial baroreflex control of cardiac output (CO) via rapid changes in heart rate (HR). Previous studies have shown that changes in HR do not always cause changes in CO, because stroke volume may vary. Whether these relationships are altered in hypertension is unknown. Using the spontaneous baroreflex sensitivity (SBRS) approach, we investigated whether baroreflex control of HR and CO were impaired after the induction of hypertension in conscious, chronically instrumented canines at rest, during mild exercise, and during exercise with metaboreflex activation (induced via reductions in hindlimb blood flow) both before and after induction of hypertension (induced via a modified Goldblatt approach--unilateral reduction in renal blood flow to >30% of control values until systolic pressure < 140 mmHg and a diastolic pressure < 90 mmHg for >30 days). After induction of hypertension, SBRS control of both HR and CO was reduced in all settings. In control, only about 50% of SBRS changes in HR caused changes in CO. This pattern was sustained in hypertension. Thus, in hypertension, the reduced SBRS in the control of HR caused reduced SBRS control of CO and this likely contributes to the increased incidence of orthostatic hypotension seen in hypertensive patients. [ABSTRACT FROM AUTHOR]