Respiratory motor control and blood pressure regulation after spinal cord injury

描述（由申请人提供）： 许多慢性脊髓损伤（SCI）患者面临着管理其不稳定血压的挑战，这通常会导致由于心输出量减少和自主神经系统功能障碍而导致的持续性低血压。此外，直立姿势下半身的血液淤积导致血压进一步降低，称为直立性低血压。这些情况严重影响SCI个体的整体健康，延迟他们参与康复治疗，限制这种治疗的有效性，并严重干扰日常生活活动。在我们的诊所，利用活动为基础的治疗方案，我们已经观察到，最常见的障碍之一，充分参与这些计划是直立性低血压。此外，直立不耐受增加了康复治疗的成本并降低了疗效。另一个常见的障碍是脊髓损伤后的康复是呼吸功能不全，由于轻瘫和麻痹的呼吸肌。在生理上，这些呼吸和心血管功能障碍密切相关。本实验室的数据显示，静息血压与肺功能结果、脊髓病变的位置和严重程度呈正相关。这些关系可能是由于更好的静脉回流到心脏，由于更高的负胸膜内压和/或更高的交感神经紧张，由于更好的压力反射反应的个人更好的吸气和呼气运动控制。我们的初步数据表明，呼吸肌训练（RMT）可以改善SCI后的呼吸运动功能，这是一种基于呼吸阻力运动的康复技术。我们观察到SCI患者在接受RMT治疗后，静息血压和立位耐力也得到改善。因此，对于目前的建议，我们假设RMT将改善慢性SCI患者的血压调节。我们将研究生理调节机制对RMT的反应。根据统计功效分析，45名慢性SCI患者将被招募参加这项为期四年的研究。所有受试者将被诊断为呼吸功能缺损和体位性低血压。我们将使用肺活量测定法、呼吸肌肌力、交感神经皮肤反应试验和呼吸肌表面肌电图来评估肺和心血管功能。此外，我们将在立位负荷试验期间连续逐搏记录全身动脉血压、心率、心输出量和测量血中儿茶酚胺水平。自主神经调节结果将通过逐搏血压和心率频率组成分析计算。我们还将评估脊髓损伤独立性（SCIM-III）和生活质量（CHART）指标。这些结果将在总共20次RMT会议之前获得，每次持续45分钟/每周5天，RMT后立即获得，并在6个月的随访期间在35名研究参与者中获得，形成实验组。另外10个人，作为对照组，将经历相同的程序，除了RMT干预，在相同的时间过程。这项技术作为一种治疗干预，以改善血压调节和研究其机制，在SCI的个人从来没有被测试过。本研究的结果将通过提高我们对肺功能和血压调节机制的理解并提供基于病理生理学的康复策略对SCI人群产生直接影响。

DESCRIPTION (provided by applicant): Many individuals with chronic spinal cord injury (SCI) face the challenge of managing their unstable blood pressure which frequently results in persistent hypotension due to decreased cardiac output and autonomic nervous system dysfunction. In addition, blood pooling in the lower body during upright posture leads to a further decrease in blood pressure known as orthostatic hypotension. These conditions severely impact the overall health of SCI individuals, delay their participation in rehabilitative treatment, limit the effectiveness of such treatment, and significantly interfere with activities of daily living. In our clinic that utilizes activity-based therapy programs, we have observed that one of the most common impediments to full participation in these programs was orthostatic hypotension. Further, orthostatic intolerance increases the cost and decreases the efficacy of rehabilitative treatment. Another common impediment to rehabilitation after SCI is respiratory insufficiency due to paresis and paralysis of respiratory muscles. Physiologically, these respiratory and cardiovascular dysfunctions are closely related. Data from our laboratory show that resting blood pressure correlates positively with pulmonary function outcomes and the location and severity of spinal cord lesion. These relationships could be due to better venous return to the heart as a result of higher negative intrapleural pressure and/or higher sympathetic tone due to better baroreflex response in individuals with better inspiratory and expiratory motor control. Our preliminary data showed that respiratory motor function after SCI can be improved by respiratory muscle training (RMT), a rehabilitative technique based on the breathing with resistance exercise. We observed that resting blood pressure and orthostatic tolerance were also improved after RMT in individuals with SCI. Therefore, for the current proposal, we hypothesize that RMT will improve blood pressure regulation in individuals with chronic SCI. We will examine the response of physiological regulatory mechanisms to RMT. Based on statistical power analysis, forty five individuals who have chronic SCI will be recruited for this study over a four-year period. All subjects will have been diagnosed as having respiratory function deficits and orthostatic hypotension. We will evaluate pulmonary and cardiovascular function using spirometry, respiratory muscle strength, sympathetic skin response tests, and surface electromyography of respiratory muscles. In addition, we will use continuous beat-to-beat recording of systemic arterial blood pressure, heart rate, cardiac output, and the measurements of blood catecholamines level during orthostatic stress test. Autonomic regulation outcomes will be calculated from beat-to-beat blood pressure and heart rate frequency composition analysis. We will also evaluate Spinal Cord Injury Independence (SCIM-III) and quality of life (CHART) measures. These outcomes will be obtained before a total of 20 RMT sessions lasting 45 minutes each / 5 days per week, immediately after RMT, and during 6-month follow-up period in 35 research participants forming the experimental group. Another 10 individuals, serving as a control group, will undergo the same procedures, except the RMT intervention, during the same time course. This technique as a therapeutic intervention in order to improve the blood pressure regulation and investigate its mechanisms in individuals with SCI has never been tested before. The results of this study will have direct effect on the SCI population by improving our understanding of the mechanisms of pulmonary function and blood pressure regulation and offering a pathophysiologically based rehabilitation strategy.