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: 8644007
• 负责人: Demetra Christou
• 金额: $ 21.9万
• 依托单位: UNIVERSITY OF FLORIDA
• 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 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8644007
• 关键词: Activities of Daily Living; Acute; Aerobic; Aerobic Exercise; Age; Aging; Ankle; Applications Grants; Arterial Occlusive Diseases; Arteries; Articular Range of Motion; Blood Vessels; Blood flow; Clinical; Clinical Research; Clinical Trials; Complex; Data; Elderly; Endothelium; Excision; Exercise; Florida; Foot-drop; Functional disorder; Funding; Future; Goals; Hindlimb; Home environment; Human; Immobilization; Inbred F344 Rats; Individual; Intervention; Investigation; Joints; Leg; Length; Measures; Modality; Modeling; Muscle; Muscle function; Muscular Atrophy; Nature; Patients; Performance; Peripheral; Peripheral arterial disease; Physical Function; Physical activity; Play; Population; Rattus; Regulation; Resistance; Rest; Skeletal Muscle; Soleus Muscle; Splint Device; Stretching; Structure of popliteal artery; Surgeon; Testing; Training; Training Programs; Translating; United States National Institutes of Health; Universities; Vasodilation; Walking; Work; aged; base; clinical practice; clinically significant; combat; design; flexibility; high risk; human subject; improved; in vivo; muscle aging; novel strategies; older patient; post stroke; preclinical study; prevent; professor; programs; public health relevance; research study; sedentary

DESCRIPTION (provided by applicant): 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 exercis 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. 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 program of daily 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 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 o the popliteal artery and lower leg resistance vasculature in sedentary, older human subjects. This work will determine whether a safe, non-invasive intervention (dorsiflexion splinting) can be used to improve endothelial function in elderly individuals. In addition, a program of daily dorsiflexion splinting, if shown to improve endothelial function in healthy older sedentary subjects, could be rapidly translated to clinical populations.

描述（由申请人提供）：骨骼肌阻力脉管系统的内皮功能随着年龄的增长而下降，导致身体活动期间肌肉血流分布不均以及老年人功能能力的丧失。尽管有氧运动训练通常用于对抗老年人的内皮功能障碍，但有氧运动训练计划的依从率较低，这通常是由于其剧烈的性质。因此，许多接受有氧训练计划的人并没有获得临床上显着的身体功能改善。需要开发可行的非药物干预措施，以增强该人群或无法进行适度有氧运动的高危患者的血流能力。低负荷、长时间的踝关节背屈可以拉伸小腿肌肉，适用于活动范围有限的患者 运动并对抗中风后患者的足下垂。肌肉长度的急剧变化会改变肌肉血流量；因此，背屈夹板造成的肌肉长度的反复、长期变化可能会改变肌肉血流的调节，并代表了增强老年人内皮功能和功能能力的可行方式。我们在大鼠衰老模型中的初步结果表明，每天使用踝背屈夹板的方案可以显着改善比目鱼肌阻力动脉的内皮依赖性血管舒张。这项工作的首要目的是检验这样的假设：每天使用踝背屈夹板可以改善老年人的内皮功能和小腿肌肉血流量。为了检验这一假设，我们将在老年 Fischer 大鼠中进行临床前研究（目标 1），并在老年人类受试者中进行临床研究（目标 2）。在目标 1 中，将在急性夹板固定期间和夹板移除后立即对下后肢肌肉的血流分布进行体内评估。每天固定夹板 4 周后，将测量休息时和步行运动期间的后肢肌肉血流量。将在离体评估阻力动脉的内皮功能，并研究有助于增强内皮依赖性扩张的内皮机制的分析。在目标 2 中，我们将检验以下假设：每天使用踝背屈夹板（4 周）可改善久坐的老年受试者的腘动脉内皮功能和小腿阻力脉管系统。这项工作将确定是否可以使用安全、非侵入性的干预措施（背屈夹板固定）来改善老年人的内皮功能。此外，如果每日背屈夹板固定计划能够改善健康老年久坐受试者的内皮功能，则可以迅速应用于临床人群。