Sleep and Breathing in Patients With Spinal Cord Injury

脊髓损伤患者的睡眠和呼吸

• 批准号: 8850249
• 负责人: M. Safwan Badr
• 金额: --
• 依托单位: JOHN D DINGELL VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8850249
• 关键词: Acetazolamide; Acute; Address; Apnea; Atelectasis; Attention; Breathing; Carbon Dioxide; Cardiovascular system; Central Sleep Apnea; Cervical; Cervical spinal cord injury; Cervical spine; Chemoreceptors; Chest; Chronic; Coin; Coughing; Data; Development; Diagnosis; Diagnostic; Failure; Frequencies; Future; General Population; Health; Health Services Accessibility; Health system; Hypercapnic respiratory failure; Hyperoxia; Hypoxia; Individual; Inequality; Investigation; Knowledge; Laboratories; Measurement; Measures; Morbidity - disease rate; Motor output; Mucous body substance; Obstructive Sleep Apnea; Operative Surgical Procedures; Oxygen; Patients; Pattern; Peripheral; Phenotype; Placebos; Plants; Population; Predisposition; Quadriplegia; Quality of life; Recurrence; Relative (related person); Reporting; Risk; Risk Factors; Sensory; Sleep; Sleep Apnea Syndromes; Sleep Disorders; Spinal Injuries; Spinal cord injury; Spinal cord injury patients; Testing; Therapeutic Intervention; Veterans; Vulnerable Populations; Wakefulness; Work; abstracting; adverse outcome; airway obstruction; effective therapy; improved; indexing; innovation; lung volume; mortality; research study; respiratory; response; tool

DESCRIPTION (provided by applicant): Abstract This proposal aims to determine the mechanisms of sleep-disordered breathing (SDB) in patients with chronic cervical spine injury, a devastating condition with very high frequency of sleep-disordered breathing. Our preliminary data demonstrated that two thirds of patients with cervical SCI demonstrated a central sleep- disordered breathing, manifesting as central sleep apnea (CSA) or periodic breathing pattern during sleep with high propensity to develop central sleep apnea (CSA), despite normal breathing during wakefulness. Understanding the fundamental mechanisms of central sleep apnea (CSA) is critically important to understanding upper airway obstruction in susceptible individuals. Our central hypothesis is that cervical SCI promotes central SDB via sleep-related hypoventilation, and hence increased plant gain, resulting in recurrent apnea/hypopnea, chronic intermittent hypoxia, and subsequent sensory long-term facilitation (LTF), manifesting by increased peripheral chemoresponsiveness and enhanced LTF following acute intermittent hypoxia. We will demonstrate that dampening peripheral chemoresponsiveness with hyperoxia, and plant gain with acetazolamide, will alleviate central apnea in these patients and may pave the way for effective treatment. Therefore, we will test the following Specific Aims: First, to determine the effect of cervical SCI on peripheral chemoreflex sensitivity. We propose to measure central and peripheral chemoreflex sensitivity tests during NREM sleep in cervical and thoracic SCI patients. We will also test the effect of dampening peripheral chemoreceptor activity in patients with cervical SCI and central apnea with hyperoxia on CSA propensity. Second, to determine the effect of acute episodic hypoxia (EH) on chemoreflex sensitivity and ventilatory long- term facilitation in patients with cervical SCI. We will test the development of ventilatory LTF following cute episodic hypoxia. Specific Aim 3 is to determine the effect of decreasing plant gain with acetazolamide on central SDB in SCI patients with central apnea or narrow CO2 reserve. We propose to compare the effect of acetazolamide vs. placebo on central apnea propensity. This work is very significant, addressing critical need for patients who suffer from disparity in access to care. This work is also innovative, identifying a new mechanism of breathing instability in this vulnerable population. innovative; we anticipate that it will yield significant new knowledge that improves the health and quality of life of these patients.

描述（由申请人提供）： 摘要：本提案旨在确定慢性颈椎损伤患者睡眠呼吸障碍 (SDB) 的机制，这是一种破坏性的疾病，发生频率非常高。 睡眠呼吸障碍。我们的初步数据表明，三分之二的颈椎 SCI 患者表现出中枢性睡眠呼吸障碍，表现为中枢性睡眠呼吸暂停 (CSA) 或睡眠期间的周期性呼吸模式，尽管睡眠期间呼吸正常，但很容易发生中枢性睡眠呼吸暂停 (CSA)。觉醒。了解中枢性睡眠呼吸暂停 (CSA) 的基本机制对于了解易感人群的上呼吸道阻塞至关重要。我们的中心假设是，颈椎 SCI 通过睡眠相关的通气不足促进中枢 SDB，从而增加植物增益，导致反复呼吸暂停/呼吸不足、慢性间歇性缺氧以及随后的感觉长期易化 (LTF)，表现为外周化疗反应性增加和急性间歇性缺氧后 LTF 增强。我们将证明，用高氧抑制外周化学反应，并用乙酰唑胺抑制植物增益，将减轻这些患者的中枢性呼吸暂停，并可能为有效治疗铺平道路。因此，我们将测试以下具体目的： 第一，确定颈椎 SCI 的效果 外周化学反射敏感性。我们建议在颈椎和胸部 SCI 患者的 NREM 睡眠期间测量中枢和外周化学反射敏感性测试。我们还将测试抑制颈椎 SCI 和高氧中枢性呼吸暂停患者的外周化学感受器活性对 CSA 倾向的影响。其次，确定急性发作性缺氧 (EH) 对颈椎 SCI 患者化学反射敏感性和通气长期促进的影响。我们将测试可爱的阵发性缺氧后通气 LTF 的发展情况。具体目标 3 是确定乙酰唑胺降低植物生长对中枢性呼吸暂停或 CO2 储备狭窄的 SCI 患者中枢 SDB 的影响。我们建议比较乙酰唑胺与安慰剂对中枢性呼吸暂停倾向的影响。这项工作非常重要，解决了遭受访问不平等的患者的迫切需求 去关心。这项工作也是创新的，确定了这种呼吸不稳定的新机制 弱势群体。创新的;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。