CE. Molecular basis for the improvement in muscle metaboreflex and mechanoreflex control in exercise-trained humans with chronic heart failure. Am J Physiol Heart Circ Physiol 307: H1655-H1666, 2014. First published October 10, 2014 doi:10.1152/ajpheart.00136.2014.-Previous studies have demonstrated that muscle mechanoreflex and metaboreflex controls are altered in heart failure (HF), which seems to be due to changes in cyclooxygenase (COX) pathway and changes in receptors on afferent neurons, including transient receptor potential vanilloid type-1 (TRPV1) and cannabinoid receptor type-1 (CB1). The purpose of the present study was to test the hypotheses: 1) exercise training (ET) alters the muscle metaboreflex and mechanoreflex control of muscle sympathetic nerve activity (MSNA) in HF patients.2) The alteration in metaboreflex control is accompanied by increased expression of TRPV1 and CB1 receptors in skeletal muscle.3) The alteration in mechanoreflex control is accompanied by COX-2 pathway in skeletal muscle. Thirty-four consecutive HF patients with ejection fractions Ͻ40% were randomized to untrained (n ϭ 17; 54 Ϯ 2 yr) or exercise-trained (n ϭ 17; 56 Ϯ 2 yr) groups. MSNA was recorded by microneurography. Mechanoreceptors were activated by passive exercise and metaboreceptors by postexercise circulatory arrest (PECA). COX-2 pathway, TRPV1, and CB1 receptors were measured in muscle biopsies. Following ET, resting MSNA was decreased compared with untrained group. During PECA (metaboreflex), MSNA responses were increased, which was accompanied by the expression of TRPV1 and CB1 receptors. During passive exercise (mechanoreflex), MSNA responses were decreased, which was accompanied by decreased expression of COX-2, prostaglandin-E2 receptor-4, and thromboxane-A2 receptor and by decreased in muscle inflammation, as indicated by increased miRNA-146 levels and the stable NF-B/ IB-␣ ratio. In conclusion, ET alters muscle metaboreflex and mechanoreflex control of MSNA in HF patients. This alteration with ET is accompanied by alteration in TRPV1 and CB1 expression and COX-2 pathway and inflammation in skeletal muscle. heart failure; muscle sympathetic nervous system; metaboreflex; mechanoreflex; exercise training

AimsWe compared the effects of exercise training on neurovascular control and functional capacity in men and women with chronic heart failure (HF). Methods and resultsForty consecutive HF outpatients from the Heart Institute, University of Sao Paulo, Brazil were divided into the following four groups matched by age: men exercise-trained (n ¼ 12), men untrained (n ¼ 10), women exercise-trained (n ¼ 9), women untrained (n ¼ 9). Maximal exercise capacity was determined from a maximal progressive exercise test on a cycle ergometer. Forearm blood flow was measured by venous occlusion plethysmography. Muscle sympathetic nerve activity (MSNA) was recorded directly using the technique of microneurography. There were no differences between groups in any baseline parameters. Exercise training produced a similar reduction in resting MSNA (P ¼ 0.000002) and forearm vascular resistance (P ¼ 0.0003), in men and women with HF. Peak VO 2 was similarly increased in men and women with HF (P ¼ 0.0003) and VE/VCO 2 slope was significantly decreased in men and women with HF (P ¼ 0.0007). There were no significant changes in left-ventricular ejection fraction in men and women with HF. ConclusionThe benefits of exercise training on neurovascular control and functional capacity in patients with HF are independent of gender.--

Exercise training improves neurovascular control and functional capacity in heart failure patients regardless of age.

These findings suggest an association between OSA and decreased metaboreflex control of MSNA. Muscle vasodilation during handgrip static exercise is preserved in patients with OSA.

Functional electrical stimulation improves muscle sympathetic nerve activity and vasoconstriction and increases exercise tolerance, muscle strength and quality of life in hospitalised heart failure patients. These findings suggest that functional electrical stimulation may be useful to hospitalised patients with decompensated chronic heart failure.

Heart failure (HF) is characterized by decreased exercise capacity, attributable to neurocirculatory and skeletal muscle factors. Cardiac resynchronization therapy (CRT) and exercise training have each been shown to decrease muscle sympathetic nerve activity (MSNA) and increase exercise capacity in patients with HF. We hypothesized that exercise training in the setting of CRT would further reduce MSNA and vasoconstriction and would increase Ca-handling gene expression in skeletal muscle in patients with chronic systolic HF. Thirty patients with HF, ejection fraction <35% and CRT for 1 mo, were randomized into two groups: exercise-trained (ET, n = 14) and untrained (NoET, n = 16) groups. The following parameters were compared at baseline and after 4 mo in each group: V̇o, MSNA (microneurography), forearm blood flow, and Ca-handling gene expression in vastus lateralis muscle. After 4 mo, exercise duration and V̇o were significantly increased in the ET group (P = 0.04 and P = 0.01, respectively), but not in the NoET group. MSNA was significantly reduced in the ET (P = 0.001), but not in NoET, group. Similarly, forearm vascular conductance significantly increased in the ET (P = 0.0004), but not in the NoET, group. The expression of the Na/Ca exchanger (P = 0.01) was increased, and ryanodine receptor expression was preserved in ET compared with NoET. In conclusion, the exercise training in the setting of CRT improves exercise tolerance and neurovascular control and alters Ca-handling gene expression in the skeletal muscle of patients with systolic HF. These findings highlight the importance of including exercise training in the treatment of patients with HF even following CRT.

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The purpose of this study was to examine the relationship between cardiac autonomic control derived from heart rate variability (HRV), high-sensitivity C-reactive protein (hs-CRP) and physical activity (PA) levels measured using accelerometers. A total of 80 healthy university students volunteered to participate in this study (20.56 ± 0.82 years, 1.36 ± 1.5 mg/L of hs-CRP). The participants were divided into groups based on tertiles of hs-CRP. Analysis of covariance adjusted to PA was used to assess group differences in HRV. Associations between hs-CRP, HRV indices and PA were analyzed using Pearson's correlation. The participants at the highest tertile of hs-CRP (tertile 3) had lower cardiac vagal modulation (SDNN, tertile 1=78.05 ± 5.9,tertile 2=82.43 ± 5.9,tertile 3=56.03 ± 6.1; SD1, tertile 1=61.27 ± 5.3, tertile 2=62.93 ± 5.4, tertile 3=40.03 ± 5.5). In addition, vagal indices were inversely correlated with hs-CRP but positively correlated with PA (SDNN r=-0.320, SD1 r=-0.377; SDNN r=0.304, SD1 r=0.299; P<0.05). Furthermore, the most physically active subjects had lower levels of hs-CRP and the highest levels of vagal modulation.