Effects of exercise training on neurovascular control and skeletal myopathy in systolic heart failure

Abstract

Neurohormonal excitation and dyspnea are the hallmarks of heart failure (HF) and have long been associated with poor prognosis in HF patients. Sympathetic nerve activity (SNA) and ventilatory equivalent of carbon dioxide (VE/VO2) are elevated in moderate HF patients and increased even further in severe HF patients. The increase in SNA in HF patients is present regardless of age, sex, and etiology of systolic dysfunction. Neurohormonal activation is the major mediator of the peripheral vasoconstriction characteristic of HF patients. In addition, reduction in peripheral blood flow increases muscle inflammation, oxidative stress, and protein degradation, which is the essence of the skeletal myopathy and exercise intolerance in HF. Here we discuss the beneficial effects of exercise training on resting SNA in patients with systolic HF and its central and peripheral mechanisms of control. Furthermore, we discuss the exercise-mediated improvement in peripheral vasoconstriction in patients with HF. We will also focus on the effects of exercise training on ventilatory responses. Finally, we review the effects of exercise training on features of the skeletal myopathy in HF. In summary, exercise training plays an important role in HF, working synergistically with pharmacological therapies to ameliorate these abnormalities in clinical practice.

Keywords: exercise training; heart failure; skeletal myopathy; sympathetic nerve activity; vasoconstriction.

Fig. 1.

Direct recording of muscle sympathetic nerve activity (MSNA) in patients with systolic heart failure, before (pre) and after (post) exercise training. Observe that exercise training causes a remarkable reduction in MSNA.

Fig. 2.

Effects of exercise training on MSNA in patients with systolic heart failure. Observe that exercise training reduces MSNA independently of pharmacological β-blocker therapy (A), sex (B), and age (C). *P < 0.05, within group difference.

Fig. 3.

Mechanisms by which a myocardial infarction, or similar injury, provokes sympathetic excitation. Lowered cardiac output decreases the arterial baroreflex inhibition on efferent MSNA, which provokes peripheral vasoconstriction. The chronic renal hypoperfusion leads to activation of the renin angiotensin system and generates skeletal muscle inflammation and atrophy. The result of these alterations is skeletal myopathy. Abnormal chemoreflex activity and abnormal skeletal muscle reflex control lead to increased ventilation. NO, nitric oxide; RSNA, renal sympathetic nerve activity.

Fig. 4.

Effects of exercise training in systolic heart failure. Note that exercise training reduces plasma and tissue renin-angiotensin system, and angiotensin II activity in the central nervous system. In addition, exercise training improves arterial baroreflex, chemoreflex, and muscle pressor reflex controls. All together, these responses lead to remarkable reduction in sympathetic nerve activity (SNA) and renal vasoconstriction and ventilatory responses (see text for more details). TRPV1, transient receptor potential vanilloid type-1.