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.

这项建议旨在研究睡眠障碍呼吸(SDB)的机制，并探索 慢性颈椎损伤(C-SCI)患者SDB的治疗方法我们发现， C-SCI患者表现为中枢性睡眠-呼吸紊乱(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相关(≤为1毫米汞柱和中等 上呼吸道压力升高(≤2cmH2O)，与呼吸力学或日间动脉血气无关。 我们在C-SCI患者中的初步数据显示，呼吸性LTF增强；因此，促进了呼吸 稳定性。因此，我们将检测C-SCI患者在SDB治疗前后睡眠中的v-LTF。 确定v-LTF升高是否是慢性间歇性预适应引起的可逆现象 缺氧或一种不变的现象，由于损伤本身。我们的初步数据还显示， C-SCI患者外周血化学反射活性的研究因此，我们将确定湿化的效果 外周补氧时的化学反应及氧减轻脑出血的影响 睡眠时呼吸不稳定。最后，我们的初步数据显示，C-SCI患者的觉醒阈值降低 病人。因此，我们将测试唑吡坦降低中枢觉醒频率的效果。 这些患者出现呼吸暂停。我们提议的议定书将解决以下具体目标。具体目标1是 检验SDB对C-SCI患者治疗将减弱vLTF和外周血细胞的假设 化学感受器活性。这一目标将通过测量急性间歇性低氧对 C-SCI患者应用SDB治疗前后的低氧后呼吸机及上呼吸道力学变化 和SDB。具体目标2是检验以下假设：抑制患者对化学感受器的敏感性 C-SCI和中央SDB补充氧气可减少中枢性呼吸事件，减少呼吸 睡眠时的可变性。这一目标将通过向C-SCI患者提供补充氧气和 中环康体发展局。具体目标3是验证唑吡坦在宫颈病变患者中应用的假设 脊髓损伤和中枢性睡眠障碍将降低呼吸相关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使用短效催眠药唑吡坦 中枢性SDB患者。这一目的也可能表明一种有效的治疗干预措施，将改善 C-SCI和中枢性SBD患者的护理。拟议中的实验将确定潜在的 神经肌肉病患者治疗中枢性SDB的一般病理生理途径 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。