Premature fatigue in veterans with heart failure: neuronal influences

患有心力衰竭的退伍军人过早疲劳：神经元影响

• 批准号: 8730935
• 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: 2014
• 资助国家: 美国
• 起止时间: 2014-10-01 至 2016-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8730935
• 关键词: Affect; Afferent Neurons; Age; American; Attenuated; Bicycling; Blood Circulation; Brain; Cardiac rehabilitation; Caring; Characteristics; Congestive Heart Failure; Corticospinal Tracts; Development; Disease; EFRAC; Electric Stimulation; Environmental air flow; Exercise; Exercise Tolerance; Exertion; Failure; Fatigue; Feedback; Fentanyl; Fiber; Foundations; Health; Heart failure; Hospitals; Human; Impairment; Individual; Isometric Contraction; Knee; Knowledge; Lead; Leg; Mediating; Morbidity - disease rate; Motor; Muscle; Neuraxis; Neurons; Patients; Peripheral; Pharmacologic Substance; Physical activity; Play; Population; Quality of life; Regulation; Rehabilitation therapy; Relative (related person); Research; Resistance; Role; Site; Source; Spinal Cord; Synapses; Techniques; Transcranial magnetic stimulation; Veterans; Walking; Work; Workload; afferent nerve; attenuation; base; design; disability; excessive exercise; femoral nerve; functional disability; improved; innovation; mortality; muscle form; outcome forecast; patient population; premature; public health relevance; quadriceps muscle; relating to nervous system; success; treatment strategy

ABSTRACT Patients with chronic heart failure (HF) are characterized by disability and exercise intolerance which impair their quality of life and depict a major source of morbidity in this population. A cardinal determinant of these characteristics is the occurrence of premature fatigue during physical activity. Based on earlier studies in healthy young humans, neural feedback from mechano- and/or metabosensitive group III and IV muscle afferents, well-known to be abnormally elevated in patients with HF, might play a key role in these abnormalities. However, even in healthy older humans, our understanding of the exact role / relative contribution of group III/IV muscle afferents to the development of fatigue during exercise is incomplete. By studying patients with HF with preserved (HFPEF) as well as reduced (HFREF) ejection fraction and age- and activity-matched healthy controls (CTRLs), we will evaluate the impact of heart failure on a) the precise development of central and peripheral fatigue during exercise, and b) the relative contribution of group III/IV muscle afferents to exercise tolerance and fatigue resistance during physical activity in humans. Specifically, we will compare the development of central and peripheral fatigue during whole body (i.e. bicycle) as well as single muscle (i.e. single leg knee-extension) exercise in HFPEF, HFREF, and CTRLs (using electric femoral nerve stimulation, electric cervicomedullary stimulation, and transcranial magnetic stimulation techniques). Furthermore, we will use lumbar intrathecal fentanyl to temporarily block the central projection of group III/IV muscle afferents during exercise (lumbar intrathecal has no concomitant effect on feedforward drive at a given absolute workload). This unique and previously proven approach to temporarily block group III/IV muscle afferent feedback will enable us to evaluate the effects of these sensory neurons on the development of central and peripheral fatigue during large and small muscle mass rhythmic exercise in CTRLS and in patients with HF. The knowledge gained from this research in humans with different types of HF will contribute to a better understanding of the role of muscle afferent feedback as a potential mechanism underlying the premature fatigue characterizing this population. Additionally, if we can confirm preliminary findings demonstrating that blocking the abnormal feedback from the muscles in HF reduces the debilitating effects of fatigue in this population, then we could provide a theoretical foundation for the design of new and innovative pharmaceutical and especially rehabilitative treatment strategies. For example, the innovation of a specific therapy that "down-regulates" the feedback from these sensory nerves to the brain and spinal cord, may effectively improve the patients' success in cardiac rehabilitation and consequently quality of life and mortality.

摘要 慢性心力衰竭（HF）患者的特点是残疾和运动 不容忍现象损害了他们的生活质量，是这方面发病率的主要来源。 人口这些特征的一个主要决定因素是早产儿的发生。 体力活动时的疲劳。根据早期对健康年轻人的研究， 来自机械和/或代谢敏感的III和IV组肌肉传入的反馈，众所周知 在HF患者中异常升高，可能在这些异常中起关键作用。 然而，即使在健康的老年人中，我们对确切的作用/相对于 III/IV组肌肉传入对运动期间疲劳发展的贡献是 不完整通过研究保留（HFPEF）和减少（HFREF）的HF患者 射血分数和年龄和活动匹配的健康对照（CTRL），我们将评估 心力衰竭对a）在治疗期间中枢和外周疲劳的精确发展的影响 运动，和B）III/IV组肌肉传入对运动耐量的相对贡献 和人体体力活动时的抗疲劳性。具体来说，我们将比较 全身（即自行车）以及单次运动期间中枢和外周疲劳的发展 HFPEF、HFREF和CTRL中的肌肉（即单腿膝关节伸展）运动（使用电动 股神经刺激、颈髓电刺激和经颅磁刺激 刺激技术）。此外，我们将使用腰椎鞘内芬太尼暂时 在运动过程中阻断III/IV组肌肉传入神经的中枢投射（腰椎鞘内 在给定的绝对工作负荷下对前馈驱动没有伴随的影响）。这一独特和 先前证明的暂时阻断III/IV组肌肉传入反馈的方法将 使我们能够评估这些感觉神经元对中枢神经系统发育的影响， CTRLS和CTRLS中大小肌肉块节律性运动期间的外周疲劳， HF患者。从这项研究中获得的知识，在人类与不同类型的 HF将有助于更好地理解肌肉传入反馈作为一种神经刺激的作用。 潜在机制的过早疲劳表征这一人群。 此外，如果我们能证实初步的发现，表明阻断异常的 HF中来自肌肉的反馈减少了该群体中疲劳的衰弱效应， 从而为新产品的设计提供理论依据 药物，特别是康复治疗策略。例如，创新 一种特殊的疗法，"下调"这些感觉神经对大脑的反馈， 和脊髓，可以有效地提高患者的心脏康复成功率， 从而影响生活质量和死亡率。