Sleep and Breathing in Patients With Spinal Cord Injury

描述(由申请人提供)： 摘要这项建议旨在确定慢性颈椎损伤患者睡眠障碍呼吸(SDB)的机制。 睡眠失调的呼吸。我们的初步数据显示，三分之二的颈椎脊髓损伤患者表现为中枢性睡眠呼吸紊乱，表现为中枢性睡眠呼吸暂停(CSA)或睡眠中周期性呼吸模式，尽管清醒时呼吸正常，但发生中枢性睡眠呼吸暂停(CSA)的可能性很高。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，颈椎脊髓损伤通过睡眠相关的低通气量促进中枢SDB，从而增加植物获得，导致反复呼吸暂停/低通气，慢性间歇性低氧，以及随后的感觉长期促进(LTF)，表现为急性间歇性低氧后外周化学反应性增强和LTF增强。我们将证明，用高氧抑制外周化学反应，用乙酰唑胺增强植物生长，将缓解这些患者的中枢性呼吸暂停，并可能为有效的治疗铺平道路。因此，我们将测试以下具体目标：第一，确定颈椎损伤的效果 对外周化学反射的敏感性。我们建议测量颈椎和胸部脊髓损伤患者在NREM睡眠期间的中枢和外周化学反射敏感性测试。我们还将测试抑制颈性脊髓损伤和中枢性呼吸暂停伴高氧患者的外周化学感受器活性对环孢素A倾向的影响。第二，探讨急性间歇性低氧(EH)对颈髓损伤患者化学反射敏感性和长期通气性的影响。我们将测试急性间歇性低氧后呼吸性LTF的发展情况。具体目标3是确定乙酰唑胺降低植物增益对伴有中枢性呼吸暂停或二氧化碳储备狭窄的脊髓损伤患者中枢SDB的影响。我们建议比较乙酰唑胺和安慰剂对中枢性呼吸暂停倾向的影响。这项工作是非常重要的，解决了患者在访问方面存在差异的迫切需求 去关心。这项工作也是创新的，发现了一种新的呼吸不稳定机制 弱势群体。创新；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。

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.