The most typical symptoms of heart failure (HF) are dyspnea and exercise intolerance. Sympathetic hyperactivation, the hallmark of HF, contributes significantly to peripheral vasoconstriction. The muscle blood flow (MBF) reduction increases oxidative stress, pro-inflammatory cytokines and contributes to changes in the phenotype of skeletal muscle. Together, these alterations lead to skeletal myopathy and reduced functional capacity in HF patients. Accumulated evidence has shown that exercise training (ET) is a safe and effective non-pharmacological therapy to the treatment of HF patients. ET improves functional capacity and quality of life in these patients. In addition, ET decreases sympathetic nerve activity and increases MBF. These responses substantially contribute to the improvement in skeletal myopathy. Recently, inspiratory muscle training (IMT) has emerged as an alternative to the treatment of HF patients. The IMT improves functional capacity and quality of life and, in addition, reduces sympathetic nerve activity and increases MBF. Thus, it is possible to hypothesize that the combination of these two non-pharmacological therapies will potentate the benefits in the treatment of HF patients. The present study aims to investigate whether the increase in the MBF after the aerobic ET plus IMT is associated with neurovascular control and angiogenic factors in HF patients. In addition, we will investigate the consequences of the increase in MBF on pro-inflammatory cytokines, oxidative stress and muscle protein balance. Finally, we will investigate the clinical implications of the changes in skeletal myopathy on exercise tolerance and quality of life of these patients.
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