Cardiovascular reflex contributions to sympathetic inhibition during low intensity dynamic leg exercise in healthy middle-age.

Aging augments resting muscle sympathetic nerve activity (MSNA) and sympatho-inhibition during mild dynamic 1-leg exercise. To elucidate which reflexes elicit exercise-induced inhibition, we recruited 19 (9 men) healthy volunteers (mean age 56 ± 9 SD years), assessed their peak oxygen uptake (VO2peak ), and, on another day, measured heart rate (HR), blood pressure (BP) and MSNA (microneurography) at rest and during 1-leg cycling (2 min each at 0 load and 30%-40% VO2peak ), 3 times: (1) seated +2 min of postexercise circulatory occlusion (PECO) (elicit muscle metaboreflex); (2) supine (stimulate cardiopulmonary baroreflexes);and (3) seated, breathing 32% oxygen (suppress peripheral chemoreceptor reflex). While seated, MSNA decreased similarly during mild and moderate exercise (p < 0.001) with no increase during PECO (p = 0.44). Supine posture lowered resting MSNA (main effect p = 0.01) BP and HR. MSNA fell further (p = 0.04) along with diastolic BP and HR during mild, not moderate, supine cycling. Hyperoxia attenuated resting (main effect p = 0.01), but not exercise MSNA. In healthy middle-age, the cardiopulmonary baroreflex and arterial chemoreflex modulate resting MSNA, but contrary to previous observations in young subjects, without counter-regulatory offset by the sympatho-excitatory metaboreflex, resulting in an augmented sympatho-inhibitory response to mild dynamic leg exercise.

Normal and excessive muscle sympathetic nerve activity in heart failure: implications for future trials of therapeutic autonomic modulation.

AIMS: Patients with sympathetic excess are those most likely to benefit from novel interventions targeting the autonomic nervous system. To inform such personalized therapy, we identified determinants of augmented muscle sympathetic nerve activity (MSNA) in heart failure, versus healthy controls. METHODS AND RESULTS: We compared data acquired in 177 conventionally-treated, stable non-diabetic patients in sinus rhythm, aged 18-79 years (149 males; 28 females; left ventricular ejection fraction [LVEF] 25 ± 11% [mean ± standard deviation]; range 5-60%), and, concurrently, under similar conditions, in 658 healthy, normotensive volunteers (398 males; aged 18-81 years). In heart failure, MSNA ranged between 7 and 90 bursts·min-1 , proportionate to heart rate (p < 0.0001) and body mass index (BMI) (p = 0.03), but was unrelated to age, blood pressure, or drug therapy. Mean MSNA, adjusted for age, sex, BMI, and heart rate, was greater in heart failure (+14.2 bursts·min-1 ; 95% confidence interval [CI] 12.1-16.3; p < 0.0001), but lower in women (-5.0 bursts·min-1 ; 95% CI 3.4-6.6; p < 0.0001). With spline modeling, LVEF accounted for 9.8% of MSNA variance; MSNA related inversely to LVEF below an inflection point of ∼21% (p < 0.006), but not above. Burst incidence was greater in ischaemic than dilated cardiomyopathy (p = 0.01), and patients with sleep apnoea (p = 0.03). Burst frequency correlated inversely with stroke volume (p < 0.001), cardiac output (p < 0.001), and peak oxygen consumption (p = 0.002), and directly with norepinephrine (p < 0.0001) and peripheral resistance (p < 0.001). CONCLUSION: Burst frequency and incidence exceeded normative values in only ∼53% and ∼33% of patients. Such diversity encourages selective deployment of sympatho-modulatory therapies. Clinical characteristics can highlight individuals who may benefit from future personalized interventions targeting pathological sympathetic activation.

Muscle Sympathetic Excitatory Response to Dynamic 1-Leg Cycling in Heart Failure With Preserved Ejection Fraction.

We provide the first description in a patient with heart failure with preserved ejection fraction of the "paradoxical," exaggerated reflex increase in muscle sympathetic nerve activity in the opposite, stationary limb during dynamic 1-leg cycling exercise that was documented previously in patients with reduced ejection fraction. (Level of Difficulty: Advanced.).