Blood flow restriction exercise to improve skeletal muscle and peripheral vascular function in person with spinal cord injuries

脊髓损伤(SCI)是一个人可以承受的最虚弱的疾病之一。 据估计，美国每年的脊髓损伤发病率为12,000例新病例。神经支配的丧失 损伤水平以下的组织肌肉会导致体力活动减少，从而导致一系列 继发性并发症包括肌肉萎缩、心血管和代谢疾病、肥胖和 血管功能障碍。这进一步导致运动不耐受、生活质量下降和抑郁。 尽管目前的康复计划侧重于提高这一人群的肌肉力量，但其疗效 这些计划中的一个受到了与伤害相关的运动障碍的挑战，这限制了运动强度 以及随后积极的肌肉适应。因此，制定一项锻炼计划 促进肌肉对小强度运动的最大适应可以极大地提高 促进脊髓损伤患者的康复，帮助恢复这些人的功能能力和生活质量。 血流限制(BFR)运动在改善肌肉大小和力量方面显示出巨大的前景 然而，在各种健康和临床人群中，BFR运动对脊髓损伤患者的好处是 没有得到证实。因此，这项功绩提案的目的是进行一项全面的研究， 探讨BFR锻炼在不完全脊髓损伤人群中的益处和风险。一般情况下，具有 慢性不完全脊髓损伤将被招募参加两个为期8周的训练期(20节)，包括 传统的伸膝/屈膝练习或屈膝/屈膝练习加血流限制。 在为期8周的干预前后将进行一系列测量，以观察肌肉的变化 和血管功能。具体目标1将确定8周的BFR运动如何影响肌肉 力量(Biodex等速测力仪)、肌肉横截面积和体积(CTcan)和疲劳 抵抗。具体目标2将确定这种新的8周训练干预对外周设备的影响 血管功能。具体地说，将确定一氧化氮介导的内皮功能的变化 通过血流介导的扩张试验，微血管网络的内皮功能将发生变化 通过评估反应性充血和动脉僵硬的变化来确定 通过测量脉搏波速度。具体目标3将重点放在BFR演习的安全性上 SCI人群。与身体健全的人相比，脊髓损伤患者发生血栓和深静脉血栓的风险更大。 个人。尽管可能性不大，但在BFR运动中引入暂时的血瘀症可能会增强 这种风险。因此，这项研究的第三个目标将是确定先天免疫激活和 血栓风险。具体地说，在整个训练干预过程中，将在多个时间点采集血液 并分析低氧诱导因子1-α，中性粒细胞细胞外陷阱(起血栓前作用) 支架)、中性粒细胞-血小板聚集物和炎症细胞因子。归根结底，如果 BFR阻力训练后的肌肉和血管功能大于传统阻力训练 经常在康复环境中进行的运动，在不增加DVT风险的情况下，应该纳入 为患有脊髓损伤的退伍军人提供长期康复计划。

Spinal cord injuries (SCI) are among the most debilitating conditions an individual can sustain with the estimates of SCI incidence in the United States at 12,000 new cases per year. The loss of innervation to the tissues muscle below the level of the lesion results in reduced physical activity which leads to an array of secondary complications including muscle atrophy, cardiovascular and metabolic disease, obesity and vascular dysfunction. This further leads to exercise intolerance, reduced quality of life and depression. Although current rehabilitative programs focus on improving muscle strength in this population, the efficacy of these programs is challenged by the injury related motor impairment, which limits the exercise intensity and subsequent positive muscular adaptations. Therefore, development of an exercise program that promotes maximal muscular adaptations to light intensity exercise could greatly improve the efficacy of rehabilitation in the SCI population and help restore functional capacity and quality of life for these individuals. Blood flow restriction (BFR) exercise has shown tremendous promise for improving muscle size and strength in a variety of healthy and clinical populations, however the benefits of BFR exercise for those with SCI has not been established. Thus, the purpose of this Merit proposal is to conduct a comprehensive study that explores the benefits and risks of BFR exercise in the incomplete SCI population. In general individuals with chronic incomplete SCI will be recruited to partake in two 8-week training periods (20 sessions) that involve traditional knee extension/flexion exercise or knee extension/flexion exercise with blood flow restriction. There will be a series of measurements before and after the 8-week intervention to look at changes in muscle and vascular function. Specific Aim 1 will determine how the 8-weeks of BFR exercise influenced muscle strength (Biodex isokinetic dynamometer), muscle cross sectional area and volume (CTscan) and fatigue resistance. Specific Aim 2 will determine how this novel 8-week training intervention impacts peripheral vascular function. Specifically, changes in nitric oxide mediated endothelial function will be determined through tests of flow mediated dilation, changes in endothelial function of the microvascular network will be determined through assessments of reactive hyperemia and changes in arterial stiffness will be determined through measurements of pulse wave velocity. Specific Aim 3 will focus on the safety of BFR exercise for the SCI population. Those with SCI are at greater risk for thrombosis and DVT compared to able bodied individuals. Although unlikely, the introduction of temporary blood stasis during BFR exercise might augment this risk. Thus, the third aim of this study will be to determine changes in innate immune activation and thrombosis risk. Specifically, blood will be collected at multiple timepoints throughout the training intervention and analyzed for hypoxia-inducible factor 1-alpha, neutrophil extra cellular traps (which act as prothrombotic scaffolds), neutrophil-platelet aggregates and inflammatory cytokines. Ultimately, if the improvements in muscle and vascular function following BFR resistance exercise is greater than the traditional resistance exercise often performed in rehabilitation settings, without increasing risk for DVT, it should be incorporated into the long-term rehabilitation programs for veterans with SCI.