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Training heart failure patients with reduced ejection fraction attenuates muscle sympathetic nerve activation during mild dynamic exercise

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posted on 21.08.2019, 11:20 by Catherine F Notarius, Philip J Millar, Daniel A Keir, Hisayoshi Murai, Nobuhiko Haruki, Emma O'Donnell, Susan Marzolini, Paul Oh, John S Floras
Muscle sympathetic nerve activity (MSNA) decreases during low intensity dynamic 1-leg exercise in healthy subjects but increases in patients with heart failure with reduced ejection fraction (HFrEF). AIMS: We hypothesized that increased peak oxygen uptake (V̇O2peak) after aerobic training would be accompanied by less sympatho-excitation during both mild and moderate 1-leg dynamic cycling; an attenuated muscle metaboreflex; and greater skin vasodilation. METHODS: We studied 27 stable, treated HFrEF patients (6 women; mean age 65 ± 2 SE years; mean left ventricular ejection fraction 30 ± 1%) and 18 healthy age-matched volunteers (6 women; mean age 57 ± 2). We assessed V̇O2peak (open-circuit spirometry); and the skin microcirculatory response to reactive hyperemia (laser flowmetry). Fibular MSNA (microneurography) was recorded before and during 1-leg cycling (2 min unloaded and 2 min at 50% of V̇O2peak ) and, to assess the muscle metaboreflex, during post-handgrip ischemia (PHGI). HFrEF patients were evaluated before and after 6 months of exercise-based cardiac rehabilitation. RESULTS: Pre-training V̇O2peak and skin vasodilatation were lower (P<0.001) and resting MSNA higher ( P=0.01) in HFrEF than control subjects. Training improved V̇O2peak (+3.0±1.0 ml·kg-1∙min-1; P<0.001) and cutaneous vasodilation and diminished resting MSNA (-6.0±2.0, P=0.01) plus exercise MSNA during unloaded (-4.0±2.5, P=0.04) but not loaded cycling (-1.0±4.0 bursts/min, P=0.34) and MSNA during PHGI ( P<0.05). CONCLUSIONS: In HFrEF patients, exercise training lowers MSNA at rest, desensitizes the sympatho-excitatory metaboreflex, and diminishes MSNA elicited by mild but not moderate cycling. Training-induced downregulation of resting MSNA and attenuated reflex sympathetic excitation may improve exercise capacity and survival.


Heart and Stroke Foundation of Ontario [grant numbers T4938, NA6298]

Canadian Institutes of Health Research [grant number PJT148836]

Natural Science and Engineering Council of Canada [grant number 06019]

Heart and Stroke/Richard Lewar Centre of Excellence

Heart and Stroke Foundation of Canada

Canadian Institutes of Health Research



  • Sport, Exercise and Health Sciences

Published in

American Journal of Physiology - Regulatory, Integrative and Comparative Physiology






R503 - R512


American Physiological Society


AM (Accepted Manuscript)

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© American Journal of Physiology - Regulatory, Integrative and Comparative Physiology

Publisher statement

This paper was accepted for publication in the journal American Journal of Physiology - Regulatory, Integrative and Comparative Physiology and the definitive published version is available at https://doi.org/10.1152/ajpregu.00104.2019.

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Dr Emma O'Donnell