Muscle metaboreflex and autonomic regulation of heart rate in humans

Abstract

Key points• Heart rate increases during exercise due to withdrawal of cardiac parasympathetic tone and increased cardiac sympathetic nerve activity.• We investigated the autonomic mechanisms whereby heart rate is regulated by the activation of metabolically sensitive skeletal muscle afferents (muscle metaboreflex).• Heart rate responses elicited by partial flow restriction during leg cycling (enhanced metaboreflex activation) and post-exercise muscle ischemia following leg cycling and handgrip (isolated metaboreflex activation) were evaluated under control (no drug), β-adrenergic blockade and parasympathetic blockade conditions. • We show that the muscle metaboreflex principally elevates heart rate by increasing cardiac sympathetic activity, and only following dynamic exercise with a large muscle mass (post-exercise muscle ischemia following leg cycling) does the partial withdrawal of cardiac parasympathetic tone make a contribution to this heart rate response.• These findings may have implications for patient populations in which alterations in skeletal muscle afferent sensitivity have been identified. AbstractWe elucidated the autonomic mechanisms whereby heart rate (HR) is regulated by the muscle metaboreflex. Eight male participants (22 ± 3 years) performed three exercise protocols: (1) enhanced metaboreflex activation with partial flow restriction (bi-lateral thigh cuff inflation) during leg cycling exercise, (2) isolated muscle metaboreflex activation (post-exercise ischaemia; PEI) following leg cycling exercise, (3) isometric handgrip followed by PEI. Trials were undertaken under control (no drug), β 1 -adrenergic blockade (metoprolol) and parasympathetic blockade (glycopyrrolate) conditions. HR increased with partial flow restriction during leg cycling in the control condition ( 11 ± 2 beats min −1 ; P < 0.05). The magnitude of this increase in HR was similar with parasympathetic blockade ( 11 ± 2 beats min −1 ), but attenuated with β-adrenergic blockade ( 4 ± 1 beats min −1 ; P < 0.05 vs. control and parasympathetic blockade). During PEI following leg cycling exercise, HR remained similarly elevated above rest under all conditions ( 11 ± 2, 13 ± 3 and 9 ± 4 beats min −1 , for control, β-adrenergic and parasympathetic blockade; P > 0.05 between conditions). During PEI following handgrip, HR was similarly elevated from rest under control and parasympathetic blockade ( 4 ± 1 vs. 4 ± 2 beats min −1 ; P > 0.05 between conditions) conditions, but attenuated with β-adrenergic blockade ( 0.2 ± 1 beats min −1 ; P > 0.05 vs. rest). Thus muscle metaboreflex activation-mediated increases in HR are principally attributable to increased cardiac sympathetic activity, and only following exercise with a large muscle mass (PEI following leg cycling) is there a contribution from the partial withdrawal of cardiac parasympathetic tone.

Autonomic Adjustments to Exercise in Humans

“…Intriguingly, HR variability analysis indicates that elevations in HR during postexercise ischemia following leg cycling are associated with reductions in cardiac parasympathetic activity (128). However, pharmacological investigations have shown that this HR elevation persists with either muscarinic or β-adrenergic blockade, implying a redundancy in the sympathetic and parasympathetic control of the heart under these conditions (83). The role of the muscle metaboreflex in cardiac autonomic control has also been evaluated by the occlusion or partial occlusion of perfusion to the exercising skeletal muscles.…”

“…Unlike postexercise ischemia, however, this maneuver engages the muscle metaboreflex whilst central command and muscle mechanoreceptors are also activated. Experimental hypoperfusion in exercising dogs (238) and humans (83) can evoke a robust increase in HR that is attenuated by β-adrenergic blockade and not affected by cardiac parasympathetic blockade. However, as β-adrenergic blockade does not entirely block this response (83,238) and as HR variability derived estimates of cardiac parasympathetic activity are reduced during leg cycling with restricted flow (128), the ability of the muscle metaboreflex to inhibit cardiac parasympathetic activity cannot be entirely ruled out.…”

Increasing blood flow to exercising muscle attenuates systemic cardiovascular responses during dynamic exercise in humans

“…It has been shown that subjects must make a greater effort to perform the same amount of work when blood flow to exercising muscles is restricted (14,19,30). In such situations, the reduced blood flow and resultant accumulation of metabolites would cause muscle fatigue, and recruitment of additional motor units would be required to maintain the same force.…”

“…In addition, the reduced blood flow and resultant accumulation of metabolites would cause muscle fatigue so that recruitment of additional motor units would be required to perform the same amount of work, and thus central command would be increased (12,14,19,30). It has been demonstrated in dogs that reducing hindlimb blood flow to ϳ50% of the free flow level during mild treadmill running elicits a systemic pressor response (5,18,25,51).…”

A cholinergic contribution to the circulatory responses evoked at the onset of handgrip exercise in humans

“…The first protocol involved isometric handgrip (n ϭ 9) and the second leg cycling exercise (n ϭ 8). Records were analyzed from previous studies (15,16) testing different hypotheses for which experimental protocols and procedures were approved by the local ethics committee (H-B-2009-024, H-3-2011-101) and undertaken in accordance with the Declaration of Helsinki. In these studies, the responses to the onset of exercise were not analyzed.…”