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，这些研究帮助定义了一种新的改进方法 对于那些高度脊髓损伤(SCI)的人来说，锻炼是必要的。脊髓损伤与更大的风险相关 心血管疾病与普通人群相比，但SCI水平高的人群 有最大的心脏代谢风险因素和最高的心脏病死亡风险。 这可能是因为那些在T3以上受伤的人骨骼和骨骼的损失最多 肺肌功能。因此，那些患有高水平脊髓损伤的人不能进行剧烈运动。 因此，有规律的有氧运动具有独特的心脏保护作用。我们已经提炼了一个 对于那些患有脊髓损伤的人来说，这是一种独特的锻炼形式，反映了健全人的锻炼方式。功能性 电刺激排训练(FESRT)将意志臂和电控相结合 腿部锻炼，产生大肌群锻炼的好处。然而，尽管有可能 通过混合FES训练失神经支配的小腿骨骼肌来提高有氧能力 运动，无法增加超过高水平脊髓损伤限制的通气量 锻炼能力。FESRT的呼吸机需求增加导致不平衡 FESRT术后通气量与全身骨骼肌需求量之间的关系。 这一观察导致了对体外呼吸支持(NIV)的探索，以改善运动 高水平SCI能力。这项研究有力地表明，NIV能显著增加有氧运动。 能力，但仅限于高水平脊髓损伤和损伤持续时间较短的人。此外, 药物治疗可能加强呼吸控制和改善运动通气性 回应。丁螺环酮可逆转大鼠脊髓损伤后的呼吸异常， 人类病例报告表明丁螺环酮成功治疗呼吸功能障碍。 因此，我们建议进行6mo的FESRT与NIV或Sham的双盲2x2试验 丁螺环酮或安慰剂用于患有急性(3岁)、高水平(T3)脊髓损伤的患者。我们假设 NIV和丁螺环酮都将改善呼吸机运动反应，并结合 治疗会有最大的效果。这将使有氧运动有更大的改善。 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克服高强度运动时的通风限制的方法。 达到SCI水平，并允许更大程度地改善心肺容量-这是一种克服 瘫痪的肺肌肉系统的机械限制和一种治疗 5-羟色胺能呼吸控制，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为既需要锻炼又需要锻炼的人群优化锻炼 并寻求锻炼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.