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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

基本信息

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
项目类别：
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

项目摘要

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.

总结：骨骼肌阻力血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量的分布不均，老年人的功能。虽然有氧运动训练通常被规定为对抗老年人血管内皮功能障碍，提高有氧运动训练依从率程序是低的，往往是由于其艰苦的性质。因此，临床显著改善在身体机能方面，许多人在有氧训练计划中并没有获得。因此，需要开发可行的非药物干预措施，这一人群或不能进行中度有氧运动的高危患者的血流量锻炼的低负荷，持续时间长的踝关节背屈，伸展肌肉的小腿，是规定在患者的活动范围有限，并对抗足下垂中风后患者肌肉长度的急性变化会改变肌肉血流量;因此，背屈夹板固定造成的肌肉长度的反复、长时间变化，调节肌肉血流，并代表一种可行的方式，以增加内皮功能和老年人的功能能力。我们在大鼠衰老模型上的初步结果表明，一个为期3周的每日持续时间延长的踝关节背屈夹板治疗计划，改善比目鱼肌阻力动脉的内皮依赖性血管舒张。的拟议工作的首要目的是检验假设，即日常表现踝关节背屈夹板可改善内皮功能和小腿肌肉血流量，老人为了验证这一假设，我们将在老年Fischer大鼠中进行临床前研究（目的1），和老年人受试者的临床研究（目的2）。在目标1中，血流分布到下部在急性夹板固定期间和夹板固定后立即在体内评价后肢肌肉的拔除.每天夹板固定4周后，在休息时测量后肢肌肉血流量，在步行锻炼时。将评估阻力动脉的内皮功能，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：背屈夹板固定（4周）改善了久坐时腘动脉的内皮功能，老年人实验对象这项工作将确定是否安全，非侵入性干预（背屈夹板）可用于改善老年人的腿部血流。另外还有按每日背屈夹板治疗计划，如果显示改善内皮功能和肌肉在健康的老年久坐受试者中的血流，可以迅速转化为临床人群。