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.
This work will determine if the addition of ventilatory support and/or the drug Buspirone improve ventilatory exercise responses in high level SCI and result in greater improvements in aerobic capacity, pulmonary function, and cardiometabolic risk. The two approaches to overcome ventilatory limitations treat mechanical constraints of paralyzed pulmonary musculature and 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.
