Premature fatigue in veterans with heart failure: neuronal influences

摘要 慢性心力衰竭患者的特点是残疾和运动。 不容忍损害了他们的生活质量，并描述了这一疾病的主要发病率来源 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。基于早期对健康年轻人的研究，神经 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 在心力衰竭患者中异常升高，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，我们对确切的角色/相对角色的理解 III/IV类肌肉传入在运动性疲劳形成中的作用 不完整。通过对保留(HFPEF)和还原(HFREF)心衰患者的研究 射血分数和年龄和活动匹配的健康对照组(CtrlS)，我们将评估 心力衰竭对a)中枢性和外周性疲劳的精确发展的影响 运动，以及b)III/IV组肌肉传入对运动耐量的相对贡献 以及人体在体力活动中的抗疲劳性。具体地说，我们将比较 全身(如自行车)和单人运动中中枢和外周疲劳的发展 HFPEF、HFREF和CtrlS中的肌肉(即单腿膝关节伸展)练习(使用电动 股神经刺激、电刺激颈髓和经颅磁力 刺激技术)。此外，我们将使用腰椎管内芬太尼暂时 运动时阻断III/IV组肌肉传入的中枢投射(腰鞘内 在给定的绝对工作负载下对前馈驱动没有伴随影响)。这是独一无二的 先前证实的暂时阻断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和大脑发育的影响 Ctrls和In大小肌群节律性运动中的外周疲劳 心衰患者。这项研究在患有不同类型心脏病的人身上获得的知识 HF将有助于更好地理解肌肉传入反馈作为一种 这一人群过早疲劳的潜在机制。 此外，如果我们能证实初步发现表明阻止异常 HF患者肌肉的反馈减少了疲劳对这一人群的衰弱作用， 从而为创新设计提供理论依据。 药物，特别是康复治疗战略。例如，创新 一种特定的疗法，“下调”从这些感觉神经到大脑的反馈 和脊髓，可以有效地提高患者的心脏康复和成功 因此，生活质量和死亡率。

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.