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

C-SCI 患者的睡眠呼吸障碍：机制和治疗

• 批准号: 9331700
• 负责人: M. Safwan Badr
• 金额: $ 29.95万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-15 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9331700
• 关键词: Acute; Address; Aftercare; Apnea; Arousal; Attention; Attenuated; Blood gas; Breathing; Carbon Dioxide; Caring; Central Sleep Apnea; Cervical; Cervical spinal cord injury; Cervical spine; Chemoreceptors; Chest; Chest wall structure; Chronic; Clinical Trials; Coin; Coughing; Data; Deafferentation procedure; Diagnosis; Diagnostic; Environmental air flow; Event; Exposure to; Failure; Frequencies; Future; Health; Health system; Hypercapnic respiratory failure; Hypoxia; Impairment; Individual; Injury; Investigation; Knowledge; Measures; Mechanics; Motor output; Neuromuscular Diseases; Obstructive Sleep Apnea; Operative Surgical Procedures; Oxygen; Pathway interactions; Patient Care; Patients; Pattern; Periodicity; Peripheral; Physical Function; Placebos; Plants; Population; Protocols documentation; Quality of life; Recurrence; Reporting; Respiratory Mechanics; Respiratory Muscles; Risk; Sensory; Sleep; Sleep Apnea Syndromes; Sleep Disorders; Spinal; Spinal Injuries; Spinal cord injury; Spinal cord injury patients; System; Testing; Therapeutic; Therapeutic Intervention; Treatment Efficacy; Wakefulness; airway obstruction; base; conditioning; effective therapy; experience; experimental study; hypnotic; improved; indexing; lung volume; neurological recovery; pharyngeal critical pressure; preconditioning; pressure; respiratory; sleep onset; tool; zolpidem

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.

该提案旨在研究睡眠呼吸障碍（SDB）的机制并探索 慢性颈椎 (C-SCI) 损伤患者的 SDB 治疗方法。我们发现 C-SCI 患者表现出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，与二氧化碳储备狭窄（≤1mmHg 和适度 上呼吸道 Pcrit 升高（≤ 2cmH2O，与呼吸力学或日间动脉血气无关。 我们对 C-SCI 患者的初步数据表明，通气 LTF 增强；从而促进呼吸 稳定。因此，我们将在 SDB 治疗前后检查 C-SCI 患者睡眠期间的 v-LTF，以 确定 v-LTF 增加是否是一种可逆现象，由于慢性间歇性预调节 由于损伤本身，缺氧或一种不可改变的现象。我们的初步数据还显示增加 C-SCI 患者的外周化学反射活动。因此，我们将确定阻尼效果 补充氧气的外周化疗反应以及 O2 缓解 CIH 的效果 睡眠时呼吸不稳定。最后，我们的初步数据显示 C-SCI 中的唤醒阈值降低 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。 这些患者出现呼吸暂停。我们提出的协议将解决以下具体目标。具体目标 1 是 检验以下假设：C-SCI 患者接受 SDB 治疗会减弱 vLTF 和外周血 化学感受器活性。这一目标将通过测量急性间歇性缺氧对身体的影响来实现。 C-SCI 患者 SDB 治疗前后缺氧后通气和上气道力学 和深圳发展银行。具体目标 2 是检验以下假设：抑制化疗患者的化学感受器敏感性 C-SCI 和中央 SDB 补充 O2 将减少中枢呼吸事件并减少呼吸 睡眠期间的变化。这一目标将通过向 C-SCI 患者提供补充氧气来实现 中央发展银行。具体目标 3 是检验以下假设：在颈椎病患者中使用唑吡坦 脊髓损伤和中枢 SDB 将降低呼吸相关的觉醒和中枢呼吸暂停指数 与安慰剂相比。为了实现这一目标，将对 C-SCI 患者使用唑吡坦（一种短效催眠药） 中枢性 SDB 患者。这一目标也可能表明一种有效的治疗干预措施，将改善 护理患有 C-SCI 和中枢性 SBD 的患者。拟议的实验将潜在地确定 治疗神经肌肉疾病患者中枢性 SDB 的通用病理生理学途径 疾病和整个 SDB 的连续体。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。