Ankle dorsiflexion splinting enhances endothelial function of aged leg muscles

踝关节背屈夹板增强老年腿部肌肉的内皮功能

• 批准号: 8956756
• 负责人: Demetra Christou
• 金额: $ 18.22万
• 依托单位: FLORIDA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-30 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8956756
• 关键词: Activities of Daily Living; Acute; Aerobic; Aerobic Exercise; Age; Aging; Ankle; Arteries; Articular Range of Motion; Blood Vessels; Blood flow; Clinical; Clinical Research; Data; Elderly; Endothelium; Excision; Exercise; Foot-drop; Future; Goals; Hindlimb; Home environment; Human; Immobilization; In Vitro; Inbred F344 Rats; Individual; Injury; Intermittent Claudication; Intervention; Leg; Length; Measures; Modality; Modeling; Muscle; Muscle function; Muscular Atrophy; Nature; Orthopedics; Patients; Performance; Peripheral arterial disease; Physical Function; Physical activity; Population; Rattus; Regulation; Resistance; Rest; Skeletal Muscle; Soleus Muscle; Splint Device; Stretching; Structure of popliteal artery; Testing; Training; Training Programs; Translating; Vasodilation; Walking; Work; aged; base; clinically significant; combat; design; endothelial dysfunction; flexibility; high risk; human subject; improved; in vivo; muscle aging; older patient; post stroke; preclinical study; prevent; programs; sedentary

Summary: Endothelial function of the skeletal muscle resistance vasculature declines with advancing age, contributing to maldistribution of muscle blood flow during physical activity and a loss of functional capacity in the elderly. Although aerobic exercise training is commonly prescribed to counter endothelial dysfunction in the elderly, the rate of compliance to aerobic exercise training programs is low, often due to their strenuous nature. Thus, clinically-significant improvements in physical function are not obtained by many individuals placed on aerobic training programs. Thus, there is a need to develop feasible non-pharmacological interventions that enhance blood flow capacity in this population or in high-risk patients who cannot perform moderate aerobic exercise. Low-load, prolonged-duration ankle dorsiflexion, which stretches the muscles of the calf, is prescribed in patients with limited range of motion and to counter foot drop in post-stroke patients. Acute changes in muscle length alter muscle blood flow; therefore, it is likely that repeated, prolonged changes in muscle length, created by dorsiflexion splinting, alter the regulation of muscle blood flow, and represent a viable modality to augment endothelial function and functional capacity in the elderly. Our preliminary results in a rat model of aging indicate that a 3-wk program of daily prolonged-duration, ankle dorsiflexion splinting dramatically improves endothelium-dependent vasodilation of resistance arteries of the soleus muscle. The overarching purpose of the proposed work is to test the hypothesis that performance of daily ankle dorsiflexion splinting improves endothelial function and lower leg muscle blood flow in the elderly. To test this hypothesis we will perform a preclinical study in aged Fischer rats (Aim 1), and clinical study in aged human subjects (Aim 2). In Aim 1, blood flow distribution to the lower hindlimb muscles will be evaluated in vivo during acute splinting and immediately following splint removal. Following 4 wks of daily splinting, hindlimb muscle blood flow will be measured at rest, and during walking exercise. Endothelial function of resistance arteries will be assessed ex vivo, and in vitro analysis of endothelial mechanisms that contribute to enhanced endothelium- dependent dilation will be investigated. In Aim 2, we will test the hypothesis that daily ankle dorsiflexion splinting (4 wks) improves endothelial function of the popliteal artery in sedentary, older human subjects. This work will determine whether a safe, non-invasive intervention (dorsiflexion splinting) can be used to improve leg blood flow in elderly individuals. In addition, a program of daily dorsiflexion splinting, if shown to improve endothelial function and muscle blood flow in healthy older sedentary subjects, could be rapidly translated to clinical populations.

概括： 骨骼肌抵抗脉管系统的内皮功能随着年龄的增长而下降， 导致体力活动期间肌肉血流分布不均和丧失 老年人的功能能力。尽管有氧运动训练通常被规定为 老年人反内皮功能障碍、有氧运动训练依从率 项目的数量很少，通常是由于其艰苦的性质。因此，临床上显着的改善 许多参加有氧训练计划的人都没有获得身体机能方面的改善。 因此，需要开发可行的非药物干预措施来增强血液 该人群或无法进行中等有氧运动的高危患者的流量 锻炼。低负荷、长时间的踝关节背屈，可以拉伸足部肌肉 小腿，用于运动范围有限的患者，并用于对抗中风后的足下垂 患者。肌肉长度的急剧变化会改变肌肉血流量；因此，很可能 由背屈夹板造成的肌肉长度的反复、长时间的变化，改变了 肌肉血流的调节，并代表增强内皮功能的可行方式 和老年人的功能能力。我们在大鼠衰老模型中的初步结果表明 为期 3 周的每日长期踝关节背屈夹板训练计划 改善比目鱼肌阻力动脉的内皮依赖性血管舒张。这 拟议工作的总体目的是检验以下假设：日常绩效 踝关节背屈夹板可改善内皮功能和小腿肌肉血流量 老年。为了检验这一假设，我们将对老年 Fischer 大鼠进行临床前研究（目标 1）， 以及老年受试者的临床研究（目标 2）。在目标 1 中，血流分布到下肢 将在急性夹板固定期间和夹板固定后立即对后肢肌肉进行体内评估 移动。每日夹板固定 4 周后，将在休息时测量后肢肌肉血流量， 以及步行锻炼时。阻力动脉的内皮功能将被评估 有助于增强内皮细胞的内皮机制的体内和体外分析 将研究相关膨胀。在目标 2 中，我们将检验以下假设：每日脚踝 背屈夹板（4周）可改善久坐时腘动脉的内皮功能， 年长的人类受试者。这项工作将确定是否有安全、非侵入性的干预措施 （背屈夹板）可用于改善老年人的腿部血流量。此外，还有一个 如果显示可以改善内皮功能和肌肉，则每日背屈夹板治疗计划 健康老年久坐受试者的血流量可以迅速转化为临床人群。

项目成果

Daily Passive Muscle Stretching Improves Flow-Mediated Dilation of Popliteal Artery and 6-minute Walk Test in Elderly Patients with Stable Symptomatic Peripheral Artery Disease.

每日被动肌肉拉伸可改善症状稳定的外周动脉疾病老年患者的腘动脉血流介导扩张和 6 分钟步行测试。

• 发表时间: 2019
• 作者: Hotta, Kazuki;Batchelor, Wayne B;Graven, James;Dahya, Vishal;Noel, Thomas E;Ghai, Akash;Katopodis, John N;Dixon, William C;Andrews, Rebecca;Pragle, Aimee;Chheda, Jegghna;Liberatore, Lia;Behnke, Brad J;Muller
• 通讯作者: Muller

Daily muscle stretching enhances blood flow, endothelial function, capillarity, vascular volume and connectivity in aged skeletal muscle.

每日肌肉拉伸可增强老年骨骼肌的血流量、内皮功能、毛细血管作用、血管容量和连接性。

• 发表时间: 2018-05-15
• 作者: Hotta, Kazuki;Behnke, Bradley J;Arjmandi, Bahram;Ghosh, Payal;Chen, Bei;Brooks, Rachael;Maraj, Joshua J;Elam, Marcus L;Maher, Patrick;Kurien, Daniel;Churchill, Alexandra;Sepulveda, Jaime L;Kabolowsky, Max B;Christou, Demetra D;Muller
• 通讯作者: Muller

Heterogeneous ageing of skeletal muscle microvascular function.

骨骼肌微血管功能的异质老化。

• 发表时间: 2016-04-15
• 作者: Muller