Divergent muscle sympathetic responses to dynamic leg exercise in heart failure and age-matched healthy subjects

Key points People with diminished ventricular contraction who develop heart failure have higher sympathetic nerve firing rates at rest compared with healthy individuals of a similar age and this is associated with less exercise capacity. During handgrip exercise, sympathetic nerve activity to muscle is higher in patients with heart failure but the response to leg exercise is unknown because its recording requires stillness. We measured sympathetic activity from one leg while the other leg cycled at a moderate level and observed a decrease in nerve firing rate in healthy subjects but an increase in subjects with heart failure. Because these nerves release noradrenaline, which can restrict muscle blood flow, this observation helps explain the limited exercise capacity of patients with heart failure. Lower nerve traffic during exercise was associated with greater peak oxygen uptake, suggesting that if exercise training attenuated sympathetic outflow functional capacity in heart failure would improve. The reflex fibular muscle sympathetic nerve (MSNA) response to dynamic handgrip exercise is elicited at a lower threshold in heart failure with reduced ejection fraction (HFrEF). The present aim was to test the hypothesis that the contralateral MSNA response to mild to moderate dynamic one-legged exercise is augmented in HFrEF relative to age- and sex-matched controls. Heart rate (HR), blood pressure and MSNA were recorded in 16 patients with HFrEF (left ventricular ejection fraction=31 +/- 2%; age 62 +/- 3years, mean +/- SE) and 13 healthy control subjects (56 +/- 2years) before and during 2min of upright one-legged unloaded cycling followed by 2min at 50% of peak oxygen uptake ((V) over dot(O2, peak) ). Resting HR and blood pressure were similar between groups whereas MSNA burst frequency was higher (50.0 +/- 2.0vs. 42.3 +/- 2.7burstsmin(-1), P=0.03) and (V) over dot(O2, peak) lower (18.0 +/- 2.0vs. 32.6 +/- 2.8mlkg(-1)min(-1), P<0.001) in HFrEF. Exercise increased HR (P<0.001) with no group difference (P=0.1). MSNA burst frequency decreased during mild to moderate dynamic exercise in the healthy controls but increased in HFrEF (-5.5 +/- 2.0vs. 6.9 +/- 1.8burstsmin(-1), P<0.001). Exercise capacity correlated inversely with MSNA burst frequency at 50% (V) over dot(O2, peak) (n=29; r=-0.64; P<0.001). At the same relative workload, one-legged dynamic exercise elicited a fall in MSNA burst frequency in healthy subjects but sympathoexcitation in HFrEF, a divergence probably reflecting between-group differences in reflexes engaged by cycling. This finding, coupled with an inverse relationship between MSNA burst frequency during loaded cycling and subjects' (V) over dot(O2, peak) , is consistent with a neurogenic determinant of exercise capacity in HFrEF.