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.

该建议旨在调查睡眠呼吸呼吸（SDB）的机制并探索 慢性颈椎（C-SCI）损伤患者SDB的治疗方法。我们发现 C-SCI患者表现出中央睡眠呼吸（SDB），表现为中央睡眠 呼吸暂停（CSA）或周期性呼吸模式，与狭窄的二氧化碳储备相关（≤1mmHg且适度 上呼吸道升高（≤2cmH2O，与呼吸力学或白天动脉血气体无关。 我们在C-SCI患者中的初步数据表明通气LTF增强了；因此，促进呼吸 稳定。因此，我们将在SDB治疗前后的C-SCI患者睡眠期间检查V-LTF 确定增加的V-LTF是否是可逆现象，这是由于慢性间歇性的预处理 由于损伤本身，缺氧或不变的现象。我们的初步数据也显示 C-SCI患者的周围化学反射活性。因此，我们将确定变性的效果 与补充氧气的外周化学疗程以及用O2对CIH减轻CIH的作用 睡眠期间呼吸不稳定。最后，我们的初步数据显示了C-SCI中的唤醒阈值降低 患者。因此，我们将测试降低Zolpidem唤醒频率对中央的效果 这些患者的呼吸暂停。我们提出的协议将解决以下特定目标。具体目标1是 检验以下假设，即在C-SCI患者中进行SDB的治疗将减弱VLTF和外周 化学感受器活性。该目标将通过测量急性发作缺氧对 C-SCI患者的SDB治疗前后SDB治疗前后的催眠后通风和上呼吸道力学 和SDB。具体目的2是检验以下假设：在 具有补充O2的C-SCI和中央SDB将减少中央呼吸事件并减少呼吸系统 睡眠期间的可变性。该目标将通过为C-SCI和患者提供补充O2来实现 中央SDB。特定目的3是检验颈椎的给药的假设 脊髓损伤和中央SDB将减少与呼吸有关的唤醒和中央呼吸暂停指数 与安慰剂相比。为了实现这一目标，Zolpidem将对C-SCI进行短效催眠 中央SDB的患者。该目标还可能表明有效的治疗干预措施将改善 护理患有C-SCI和中央SBD的患者。提出的实验将可能识别 神经肌肉患者中央SDB治疗中央SDB的可概括的病理生理途径 疾病以及整个SDB的连续体。我们预计它将产生重大的新知识 改善这些患者的健康和生活质量。