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：
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
项目类别：
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

项目摘要

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）：随着年龄的增长，骨骼肌抵抗脉管的内皮功能下降，有助于体育锻炼期间肌肉血流的Maldistripution，并且老年人的功能能力丧失。尽管有氧运动训练通常是针对老年人的内皮功能障碍的规定，但对有氧运动训练计划的遵守率通常是由于其剧烈的性质。因此，在有氧培训计划中，许多人无法获得临床上显着的身体机能改善。有必要开发可行的非药物干预措施，以增强该人群的血流量或无法进行中等有氧运动的高危患者。在范围有限运动后患者的运动和脚步下降。肌肉长度的急性改变会改变肌肉血流；因此，通过背屈夹板产生的重复，长时间的肌肉长度变化，改变了肌肉血流的调节，并代表了增强老年人内皮功能和功能能力的可行方式。我们的初步导致大鼠衰老模型表明，每日脚踝背屈夹板的程序显着改善了比索鲁斯肌肉的耐药性动脉的内皮血管舒张。拟议工作的总体目的是检验以下假设：每天的脚踝背屈夹板的表现可改善老年人的内皮功能和较低的腿部肌肉血流。为了检验这一假设，我们将在老年大鼠（AIM 1）和年龄人类受试者的临床研究中进行临床前研究（AIM 2）。在AIM 1中，将在急性夹板期间和夹板去除后立即在体内评估血流到下后肢肌肉的血流分布。每天4周夹板后，将在静止和步行过程中测量后肢肌肉血流。将在体内评估抗性动脉的内皮功能，并将研究有助于增强内皮依赖性扩张的内皮机制。在AIM 2中，我们将测试以下假设：每天的脚踝背屈夹板（4周）改善内皮功能o popliteal动脉和久坐的老年人受试者中的popliteal动脉和较低的腿部抗性脉管系统。这项工作将确定是否可以使用安全的非侵入性干预（背屈夹板）来改善老年人的内皮功能。此外，如果显示出可改善健康久乎久坐受试者内皮功能的每日背屈夹板程序，则可以迅速转化为临床人群。