Microneurographic characterization of sympathetic responses during 1-leg exercise in young and middle-aged humans

Muscle sympathetic nerve activity (MSNA) at rest increases with age. However, the influence of age on MSNA recorded during dynamic leg exercise is unknown. We tested the hypothesis that aging attenuates the sympatho-inhibitory response observed in young subjects performing mild to moderate 1-leg cycling. After pre-determining peak oxygen uptake (VO2peak), we compared contra-lateral fibular nerve MSNA during 2 minutes each of mild (unloaded) and moderate (30-40% of the work rate at peak VO2, halved for single leg) 1-leg cycling in 18 young (23±1 years [mean±SE]) and 18 middle-aged (57±2 years) sex-matched healthy subjects. Mean height, weight, resting heart rate (HR), systolic blood pressure (BP) and percent predicted VO2peak were similar between groups. Middle-aged subjects had higher resting MSNA burst frequency and incidence (P<0.001) and diastolic BP (P=0.04). During moderate 1-leg cycling, older subjects’ systolic BP increased more (+21±5 vs.+10±1 mmHg; P=0.02) and their fall in MSNA burst incidence was amplified (-19±2 vs. -11±2 bursts/100heartbeats; P=0.01) but because HR rose less (+153 vs.+192 bpm; P=0.03), exercise induced similar reductions in burst frequency (P=0.25). Contrary to our initial hypothesis, with advancing age, mild to moderate intensity dynamic leg exercise elicits a greater rise in systolic BP and a larger fall in MSNA

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

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