Efficacy of exercise training in patients with HFpEF

摘要 射血分数保留的心力衰竭（HFpEF）患者的特征是运动不耐受 以及体力活动时的过早疲劳。神经反馈介导的异常运动升压反射 来自机械和/或代谢敏感的III和IV组肌肉传入可能有助于这些衰弱 症状然而，很少有人知道的作用和相对贡献的第III/IV类传入在循环中， HFpEF患者的控制和疲劳发展。通过研究HFpEF患者和匹配良好的 对照组，我们将评估这些肌肉传入对循环控制和疲劳的贡献 发展，因素被认为是主要贡献者行使不容忍。我们将使用腰椎鞘内注射 芬太尼阻断在自愿和被动运动过程中III/IV组肌肉传入神经的中枢投射（无 对前馈驱动的伴随效应）。这种经过验证的方法将使我们能够评估和区分 之间，第III组和第IV组肌肉传入对中枢和外周血流动力学的影响， 运动，运动引起的中枢和外周疲劳的发展（股神经刺激 技术）和运动耐力。我们还将研究肌肉形态测量学、压力反射和化学反射 敏感性，并研究运动过程中股四头肌肌内代谢的变化， 31磷磁共振波谱评价心血管反射疾病相关改变 敏感性和内在肌肉特征作为决定循环控制改变的潜在因素 HFpEF患者的抗疲劳性。最后，我们将在监督12周后重复这些研究， 膝关节伸展运动训练计划，使我们能够调查慢性运动的作用， 第III/IV组肌肉传入的血流动力学反应，运动，疲劳的发展，和， 最后，锻炼耐力。如果这个项目证实了III/IV组肌肉传入神经对 HFpEF患者表现出的运动不耐受，长期运动可以缓解这些情况 损伤，拟议的工作将提供科学依据，在治疗这一范式转变 人口增长。

ABSTRACT Patients with heart failure with preserved ejection fraction (HFpEF) are characterized by exercise intolerance and premature fatigue during physical activity. An abnormal exercise pressor reflex mediated by neural feedback from mechano- and/or metabosensitive group III and IV muscle afferents may contribute to these debilitating symptoms. However, little is known about the role and relative contribution of group III/IV afferents in circulatory control and fatigue development in patients with HFpEF. By studying both patients with HFpEF and well-matched controls, we will evaluate the contribution of these muscle afferents to circulatory control and fatigue development, factors recognized to be major contributors to exercise intolerance. We will use lumbar intrathecal fentanyl to block the central projection of group III/IV muscle afferents during voluntary and passive exercise (no concomitant effect on feedforward drive). This proven approach will enable us to evaluate, and distinguish between, the effects of group III and IV muscle afferents on central and peripheral hemodynamics during exercise, the exercise-induced development of central and peripheral fatigue (femoral nerve stimulation techniques), and on exercise tolerance. We will also study muscle morphometry, baroreflex and chemoreflex sensitivity, and investigate intramuscular metabolic changes of the quadriceps during exercise using 31phosphorus magnetic resonance spectroscopy to evaluate disease-related alterations in cardiovascular reflex sensitivity and intrinsic muscle characteristics as a potential factor determining alterations in circulatory control and fatigue resistance in patients with HFpEF. Finally, we will repeat these studies after a supervised 12-week knee-extension exercise training program, allowing us to investigate the effect of chronic exercise on the role of group III/IV muscle afferents in the hemodynamic response to exercise, the development of fatigue, and, ultimately, exercise tolerance. If this project confirms a significant contribution of group III/IV muscle afferents to the exercise intolerance exhibited by patients with HFpEF, and that chronic exercise can alleviate these impairments, the proposed work will provide the scientific basis for a paradigm shift in the treatment of this growing population.