Sleep-Disordered Breathing in patients with C-SCI: Mechanisms and Therapy

本研究旨在探讨睡眠呼吸障碍（SDB）的发生机制， 慢性颈椎损伤患者SDB的治疗方法。我们发现 C-SCI患者表现为中枢性睡眠呼吸障碍（SDB），表现为中枢性睡眠 呼吸暂停（CSA）或周期性呼吸模式，与狭窄的CO2储备（≤ 1 mmHg和中度 上气道压积升高（≤ 2cmH 2 O），与呼吸力学或日间动脉血气无关。 我们在C-SCI患者中的初步数据表明，增强的缓解性LTF;因此， 稳定因此，我们将在SDB治疗前后检测C-SCI患者睡眠期间的v-LTF， 确定v-LTF增加是否是一种可逆现象，由于慢性间歇性预处理 缺氧或不可改变的现象，由于损伤本身。我们的初步数据还显示， C-SCI患者外周化学反射活性。因此，我们将确定阻尼的效果 补充氧气的外周化学反应性和O2缓解CIH的作用， 睡眠时呼吸不稳定。最后，我们的初步数据显示C-SCI患者的唤醒阈值降低， 患者因此，我们将测试唑吡坦降低觉醒频率对中枢神经系统的影响。 这些患者的呼吸暂停。我们提出的协议将解决以下具体目标。具体目标1是 检验在C-SCI患者中治疗SDB将减弱vLTF和外周血淋巴细胞的假设。 化学感受器活性这一目标将通过测量急性发作性缺氧对 脊髓损伤患者SDB治疗前后的低氧通气和上气道力学 和SDB。具体目的2是检验抑制患有癌症的患者中的化学感受器敏感性的假设。 补充O2的C-SCI和中央SDB将减少中央呼吸事件， 睡眠中的变化。这一目标将通过向C-SCI患者提供补充O2来实现， 中央SDB。具体目标3是检验宫颈癌患者服用唑吡坦的假设 脊髓损伤和中枢性SDB将减少与麻醉相关的觉醒和中枢性呼吸暂停指数 与安慰剂相比。为了达到这一目的，将对C-SCI给予短效催眠药唑吡坦 中心性SDB患者。这一目标也可能表明一种有效的治疗干预， 护理患有C-SCI和中央SBD的患者。拟议的实验将确定潜在的 神经肌肉萎缩患者中枢性SDB治疗的可推广病理生理途径 疾病和SDB的连续性。我们预计，它将产生重要的新知识， 改善这些患者的健康和生活质量。

This proposal aims to investigate the mechanisms of sleep-disordered breathing (SDB) and to explore therapeutic approaches for SDB in patients with chronic cervical spine (C-SCI) injury. We have discovered that patients with C-SCI demonstrate a central sleep-disordered breathing (SDB), manifesting as central sleep apnea (CSA) or periodic breathing pattern, associated with narrow CO2 reserve (≤1mmHg and modestly elevated upper airway Pcrit (≤ 2cmH2O, independent of respiratory mechanics or daytime arterial blood gases. Our preliminary data in patients with C-SCI demonstrated enhanced ventilatory LTF; thus, promoting breathing stability. Therefore, we will examine v-LTF during sleep in C-SCI patients before and after treatment of SDB to determine if increased v-LTF is a reversible phenomenon, due to pre-conditioning with chronic intermittent hypoxia OR an immutable phenomenon, due to the injury per se. Our preliminary data also reveal increased peripheral chemoreflex activity in patients with C-SCI. Therefore, we will determine the effect of dampening peripheral chemoresponsiveness with supplemental oxygen and the effect of alleviating CIH with O2 on breathing instability during sleep. Finally, our preliminary data showed decreased arousal threshold in C-SCI patients. Therefore , we will test the effect of decreasing the frequency of arousals with Zolpidem on central apnea in these patients. Our proposed protocols will address the following Specific Aims. Specific Aim 1 is to test the hypothesis that treatment of SDB in patients with C-SCI will attenuate vLTF and peripheral chemoreceptor activity. This aim will be accomplished by measuring the effect of acute episodic hypoxia on post-hypoxic ventilation and upper airway mechanics before and after treatment of SDB in patients with C-SCI and SDB. Specific Aim 2 is to test the hypothesis that dampening chemoreceptor sensitivity in patients with C-SCI and central SDB with supplemental O2 will reduce central respiratory events and decrease respiratory variability during sleep. This aim will be accomplished by providing supplemental O2 to patients with C-SCI and central SDB. Specific Aim 3 is to test the hypothesis that administration of zolpidem, in patients with cervical spinal cord injury and central SDB will decrease respiratory-related arousals and the central apneas index compared to placebo. To accomplish this aim, Zolpidem, a short-acting hypnotic will be administered to C-SCI patients with central SDB. This aim may also indicate an effective therapeutic intervention that will improve the care of patients suffering with C-SCI and central SBD. The proposed experiments will identify potentially generalizable pathophysiologic pathways for the treatment of central SDB in patients with neuromuscular disease and across the continuum of SDB. We anticipate that it will yield significant new knowledge that improves the health and quality of life of these patients.