HYBRID-FES EXERCISE TO PREVENT CARDIOPULMONARY DECLINES IN ACUTE HIGH LEVEL SCI

这项研究建立在先前资助的研究的基础上，这些研究有助于定义一种新的方法来改善 脊髓损伤（spinal cord injury，SCI）患者的运动。SCI与更大的风险相关 对于心血管疾病相比，一般人群，但那些高水平的SCI 具有最大的心脏代谢风险因素和最高的心脏病死亡风险。 这可能是因为那些受伤超过T3的人有最多的骨骼损失， 肺肌功能因此，那些高水平SCI的人不能进行高强度的运动 从而产生有规律的有氧运动所特有的心脏保护作用。我们提炼了一种 为SCI患者提供一种独特的运动方式，反映了身体健全者的运动。功能 电刺激行训练（FESRT）耦合意志手臂和电控制 腿部锻炼，产生大肌肉群锻炼的好处。尽管有潜力 用于通过混合FES训练失神经腿部骨骼肌来增强有氧能力 运动，无法增加通气超过高水平SCI限制的限制 运动能力FESRT的解释性要求的增加导致了不平衡 FESRT后的排便能力和更大的全身骨骼肌需求之间的关系。 这一观察结果导致了探索外部辅助支持（NIV），以改善运动 高水平SCI的能力。这项工作有力地表明，NIV急性增加有氧 能力，但仅在那些高级别的SCI和较短的损伤持续时间。此外，本发明还提供了一种方法， 药物治疗可以增强呼吸控制，改善运动后的 应答丁螺环酮可以逆转大鼠SCI后的呼吸异常，并且 人类病例报告表明成功的丁螺环酮治疗呼吸功能障碍。 因此，我们提出了一项6个月FESRT + NIV或Sham的双盲2x2试验， 丁螺环酮或安慰剂用于急性（<3岁）、高水平（>T3）SCI患者。我们假设 NIV和丁螺环酮都能改善运动反应， 治疗效果最好。这将导致更大的改善有氧运动 容量和伴随的肺功能增加和心脏代谢减少 风险这项工作提出了两种方法，以克服限制行使在高 水平SCI，并允许心肺功能的更大改善-一个克服 麻痹的肺肌肉组织的机械限制和治疗肺功能丧失的方法 β-肾上腺素能呼吸控制，这两者都可能导致迟钝的呼吸反应。 这项研究的最终目的是优化运动的人口， 并寻求运动所能带来的广泛益处。

This research builds on prior funded research that helped to define a novel approach to improve exercise for those with high level spinal cord injuries (SCI). SCI is associated with greater risk for cardiovascular disease compared to the general population, but those with high level SCI have the greatest cardiometabolic risk factors and highest risk of mortality due to heart disease. This is likely due to the fact that those with injuries above T3 have the most loss of skeletal and pulmonary muscle function. As a result, those with high level SCI cannot exercise at intensities resulting in the unique cardioprotective effects of regular aerobic exercise. We have refined a unique form of exercise for those with SCI that mirrors exercise in the able-bodied. Functional Electrical Stimulation Row Training (FESRT) couples volitional arm and electrically controlled leg exercise, resulting in the benefits of large muscle mass exercise. However, despite potential for enhancing aerobic capacity by training the denervated leg skeletal muscle via hybrid FES exercise, the inability to increase ventilation beyond limits set by high level SCI restricts exercise capacity. The increase in ventilatory requirements with FESRT results in an imbalance between ventilatory capacity and greater whole body skeletal muscle demand after FESRT. This observation led to the exploration of external ventilatory support (NIV) to improve exercise capacity in high level SCI. This work strongly suggests that NIV acutely increases aerobic capacity, but only in those with high level SCI and shorter injury duration. In addition, pharmacologic treatments may augment respiratory control and improve exercise ventilatory responses. Buspirone can reverse respiratory abnormalities consequent to SCI in rats, and humans case reports suggest successful Buspirone treatment of respiratory dysfunction. Therefore, we propose a double-blind 2x2 trial of 6mo of FESRT with NIV or Sham and Buspirone or Placebo in individuals with acute(<3 years), high-level (>T3) SCI. We hypothesize that both NIV and Buspirone will improve ventilatory exercise responses and that combined treatment will have the greatest effect. This will result in greater improvements in aerobic capacity and concomitant increases in pulmonary function and reductions in cardiometabolic risk. This work proposes two approaches to overcome ventilatory limitations to exercise in high level SCI and allow for greater improvements in cardiopulmonary capacity - one that overcomes mechanical limitations of paralyzed pulmonary musculature and one that treats loss of serotonergic respiratory control, both of which may contribute to blunted ventilatory responses. The ultimate purpose of this research is to optimize exercise for a population that both needs and seeks the broad range of benefits that exercise can confer.