Efficacy of exercise training in patients with HFpEF

运动训练对 HFpEF 患者的疗效

• 批准号: 10063375
• 负责人: MARKUS AMANN
• 金额: --
• 依托单位: VA SALT LAKE CITY HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-10-01 至 2025-09-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10063375
• 关键词: Activities of Daily Living; Admission activity; Affect; Attenuated; Baroreflex; Blood flow; Cardiovascular system; Characteristics; Chronic; Complex; Development; Disease; Dyspnea; EFRAC; Exercise; Exercise Tolerance; Exertion; Exhibits; Extensor; Failure; Fatigue; Feedback; Fentanyl; Fiber; Goals; Health; Healthcare Systems; Heart Rate; Heart failure; Impairment; Individual; Intramuscular; Knee; Leg; Limb structure; Link; Magnetic Resonance Spectroscopy; Mediating; Metabolic; Morbidity - disease rate; Mortality Decline; Movement; Muscle; Muscle Fatigue; Nerve; Patients; Perception; Peripheral; Pharmacotherapy; Physical activity; Play; Population; Procedures; Quality of life; Reflex action; Research; Resistance; Role; Source; Supervision; Symptoms; Techniques; Training; Training Programs; Vascular resistance; Veterans; Work; alternative treatment; blood pressure reduction; blood pressure regulation; cardiorespiratory fitness; comorbidity; disability; disabling symptom; exercise intervention; exercise intolerance; exercise training; femoral nerve; functional decline; heart function; hemodynamics; improved; morphometry; mortality; premature; preservation; quadriceps muscle; readmission rates; reduce symptoms; relating to nervous system; response; treatment strategy; willingness

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.

抽象的 射血分数保留的心力衰竭 (HFpEF) 患者的特点是运动不耐受 体力活动期间过早疲劳。由神经反馈介导的异常运动加压反射 来自机械和/或代谢敏感的 III 组和 IV 组肌肉传入可能会导致这些衰弱 症状。然而，人们对 III/IV 组传入神经在循环系统中的作用和相对贡献知之甚少。 HFpEF 患者的控制和疲劳发展。通过研究 HFpEF 和匹配良好的患者 控制，我们将评估这些肌肉传入对循环控制和疲劳的贡献 发展，被认为是导致运动不耐受的主要因素。我们将使用腰椎鞘内注射 芬太尼在自愿和被动运动期间阻断 III/IV 组肌肉传入的中央投射（无 对前馈驱动的伴随影响）。这种经过验证的方法将使我们能够评估和区分 III 组和 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（股神经刺激 技术），以及运动耐力。我们还将研究肌肉形态测量、压力反射和化学反射 敏感性，并研究运动过程中股四头肌的肌内代谢变化 31磷磁共振波谱评估心血管反射中疾病相关的改变 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 患者的疲劳抵抗力。最后，我们将在为期 12 周的监督后重复这些研究 膝关节伸展运动训练计划，使我们能够研究长期运动对膝关节功能的影响 III/IV 组肌肉传入对运动的血流动力学反应、疲劳的发展，以及 最后，锻炼耐受力。如果该项目证实 III/IV 组肌肉传入对 HFpEF 患者表现出的运动不耐受，长期运动可以缓解这些症状 损伤，拟议的工作将为治疗这种疾病的范式转变提供科学基础 人口不断增长。