Efficacy of exercise training in patients with HFpEF

摘要 射血分数保留的心力衰竭患者的特点是运动耐量不足。 以及在体力活动中的过早疲劳。神经反馈介导的运动加压反射异常 机械和/或代谢敏感的III和IV组肌肉传入可能与这些衰弱有关 症状。然而，关于III/IV类传入神经在循环中的作用和相对贡献，我们知之甚少。 HFpEF患者的控制和疲劳发展。通过对HFpEF患者和完全匹配的患者进行研究 对照，我们将评估这些肌肉传入对循环控制和疲劳的贡献。 发展，被认为是造成运动不容忍的主要因素。我们将使用腰椎鞘内注射 芬太尼阻断自主和被动运动中III/IV组肌肉传入的中枢投射(NO 前馈驱动的伴随效应)。这一成熟的方法将使我们能够评估和区分 Ⅲ、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)，以及运动耐量。我们还将学习肌肉形态测量、压力反射和化学反射。 敏感性，并观察运动过程中股四头肌的肌内代谢变化 31P磁共振波谱评价心血管反射的疾病相关性改变 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，我们将在有监督的12周后重复这些研究 伸膝运动训练计划，让我们调查慢性运动对作用的影响 III/IV组肌肉传入运动的血流动力学反应，疲劳的发展，以及， 归根结底，要锻炼耐性。如果该项目确认III/IV组肌肉传入对 HFpEF患者表现出的运动不耐受，而慢性运动可以缓解这些 关于损伤，拟议的工作将为治疗这一问题的范式转变提供科学基础 不断增长的人口。

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.