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; 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 心力衰竭和保留的射血分数（HFPEF）的患者的特征是运动不耐受 和体育锻炼期间过早疲劳。神经反馈介导的异常运动式训练反射 从机械和/或代谢敏感的第三组和IV肌肉传入可能会导致这些使人衰弱 症状。但是，关于第三组/IV组传入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育。通过研究HFPEF和匹配良好的患者 控制措施，我们将评估这些肌肉传入对循环控制和疲劳的贡献 发展，被认为是行使不宽容的主要因素。我们将使用腰椎 芬太尼在自愿运动和被动锻炼过程中阻止III/IV肌传入的中心投影（否 对前驱动驱动的效果）。这种经过验证的方法将使我们能够评估和区分 在III组和IV肌肉传入对中央和周围血液动力学的影响之间 运动，运动引起的中枢和周围疲劳的发展（股神经刺激 技术）和运动耐受性。我们还将研究肌肉形态计量学，降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磷磁共振光谱法以评估心血管反射的疾病相关改变 灵敏度和内在肌肉特征是决定循环控制改变的潜在因素 HFPEF患者的疲劳性耐药性。最后，我们将在有监督的12周后重复这些研究 膝盖扩张运动训练计划，使我们能够研究慢性运动对 III/IV组的肌肉传入在血液动力学反应中，疲劳的发展以及 最终，耐受性。如果该项目证实了III/IV组肌肉传入的重大贡献 HFPEF患者表现出的运动不耐受性，慢性运动可以减轻这些 损害，拟议的工作将为治疗的范式转移提供科学基础 人口增长。