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.

抽象的 慢性心力衰竭（HF）的患者的特征是残疾和运动 损害其生活质量并描绘出主要发病率的不宽容 人口。这些特征的基本决定因素是出现过早的 体育锻炼期间的疲劳。基于对健康的年轻人的早期研究，神经 机械和/或代谢敏感组III和IV肌肉传入的反馈，众所周知 HF患者的异常升高可能会在这些异常中起关键作用。 但是，即使在健康的老年人中，我们对确切角色 /相对的理解 III/IV组肌肉传入对运动过程中疲劳发展的贡献是 不完整。通过研究HF的患者（HFPEF）以及降低（HFREF） 射血分数以及年龄和活动匹配的健康对照（CTRL），我们将评估 心力衰竭对a）中心和周围疲劳的精确发展 锻炼，b）III/IV组肌肉传入对行使耐受性的相对贡献 和人类体育活动期间的疲劳性抗性。具体来说，我们将比较 全身（即自行车）以及单身的中央和外围疲劳的发展 HFPEF，HFREF和CTRLS中的肌肉（即单腿膝盖扩张）运动（使用电气 股神经刺激，电宫颈刺激和经颅磁 刺激技术）。此外，我们将使用腰部鞘内芬太尼暂时 阻止运动过程中III/IV组肌肉传入的中心投影（腰椎鞘内 在给定的绝对工作负载下，对前驱动驱动没有效果。这个独特的和 以前证明的方法是暂时阻止III/IV组的肌肉传入反馈 使我们能够评估这些感觉神经元对中央和中心发展的影响 在CTRL中和小肌肉质量节奏运动中的外围疲劳和 HF患者。这项研究从具有不同类型的人类中获得的知识 HF将有助于更好地理解肌肉传入的反馈作用 表征该人群的过早疲劳的潜在机制。 此外，如果我们可以确认初步发现，证明阻止异常 HF中肌肉的反馈减少了疲劳在该人群中的衰弱作用， 然后，我们可以为设计新创新的设计提供理论基础 药物，尤其是康复治疗策略。例如，创新 从这些感觉神经向大脑的反馈“下调”的特定疗法 和脊髓，可以有效地改善患者在心脏康复方面的成功和 因此，生活质量和死亡率。