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

Catherine F Notarius,Paul Oh,John S Floras,Daniel A Keir,Nobuhiko Haruki,Philip J Millar,Emma O’Donnell,Susan Marzolini,Hisayoshi Murai

doi:10.1152/ajpregu.00104.2019

Abstract

Muscle sympathetic nerve activity (MSNA) decreases during low-intensity dynamic one-leg exercise in healthy subjects but increases in patients with heart failure with reduced ejection fraction (HFrEF). We hypothesized that increased peak oxygen uptake (V̇o2peak) after aerobic training would be accompanied by less sympathoexcitation during both mild and moderate one-leg dynamic cycling, an attenuated muscle metaboreflex, and greater skin vasodilation. We studied 27 stable, treated HFrEF patients (6 women; mean age: 65 ± 2 SE yr; mean left ventricular ejection fraction: 30 ± 1%) and 18 healthy age-matched volunteers (6 women; mean age: 57 ± 2 yr). We assessed V̇o2peak (open-circuit spirometry) and the skin microcirculatory response to reactive hyperemia (laser flowmetry). Fibular MSNA (microneurography) was recorded before and during one-leg cycling (2 min unloaded and 2 min at 50% of V̇o2peak) and, to assess the muscle metaboreflex, during posthandgrip ischemia (PHGI). HFrEF patients were evaluated before and after 6 mo of exercise-based cardiac rehabilitation. Pretraining 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). In HFrEF patients, exercise training lowers MSNA at rest, desensitizes the sympathoexcitatory 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.

Highlights

Two characteristics of patients with heart failure and reduced left ventricular ejection fraction (HFrEF) that predict independently foreshortened survival are diminished exercise capacity and augmented resting state sympathetic nervous system activity [8, 16, 33, 38, 53]
Skin blood flow (SBF) was calculated from changes in red blood cell flux assessed by laser Doppler flowmetry (Periflux 5001; Perimed, Ardmore, PA), a noninvasive measure of microcirculatory function made by placing a probe on the forearm 10 cm distal to the antecubital fossa
After stabilization with skin temperature constant, a 5-min recording of skin blood flow was acquired at rest, to assess forearm skin vasodilatory capacity, during 5 min of reactive hyperemia induced by 3 min of brachial artery occlusion

Summary

Introduction

Two characteristics of patients with heart failure and reduced left ventricular ejection fraction (HFrEF) that predict independently foreshortened survival are diminished exercise capacity and augmented resting state sympathetic nervous system activity [8, 16, 33, 38, 53]. Interventions such as exercise training that moderate these abnormalities and have, as well, the potential to alleviate symptom burden and prolong life expectancy are of great interest to the heart failure community [16, 54]. Several trials from a single center involving cohorts with HFrEF reported training-induced reductions in resting MSNA [42, 48]

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Results

Conclusion