Cardiovascular Responses to Sleep Apnea in Tetraplegia: A Pilot Study

四肢瘫痪患者睡眠呼吸暂停的心血管反应：一项初步研究

• 批准号: 8053777
• 负责人: Gregory J. Schilero
• 金额: --
• 依托单位: JAMES J PETERS VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8053777
• 关键词: Acids; Acute; Aldosterone; Apnea; Atrial Natriuretic Factor; Blood Pressure; Body Surface Area; Bradycardia; C-reactive protein; Cardiac; Cardiac Output; Cardiovascular Diseases; Cardiovascular system; Catecholamines; Chronic; Data; Development; Diagnosis; Event; Fostering; General Population; Goals; Heart Atrium; Human; Hypertension; Hypoxemia; Hypoxia; Individual; Interleukin-6; Investigation; Kidney; Lead; Medical; Metanephrine; Mission; Modeling; Muscle; Myocardial Infarction; Obstructive Sleep Apnea; Oxidative Stress; Paralysed; Patient Care; Persons; Pilot Projects; Plasma; Population; Prevalence; Quadriplegia; Quality of life; REM Sleep; Relative (related person); Renin; Renin-Angiotensin System; Respiratory Paralysis; Rest; Risk; Serum; Severities; Sleep; Sleep Apnea Syndromes; Sleep Stages; Stress; Stretching; Stroke; Surrogate Markers; Sympathectomy; Sympathetic Nervous System; Up-Regulation; Vasoconstrictor Agents; Veterans; Woman; Work; attributable mortality; base; cardiovascular disorder risk; chronotropic; endothelial dysfunction; falls; hemodynamics; hypoperfusion; improved; indexing; men; mortality; pressure; response; screening; stem; treatment effect; urinary; vascular inflammation

DESCRIPTION (provided by applicant): Screening studies suggest that the prevalence of moderate to severe obstructive sleep apnea (OSA) in persons with tetraplegia ranges from 22% to 36%, thus greatly exceeding prevalence estimates of 9.1% in men and 4% in women encountered in the general population. Recent evidence indicates that untreated OSA carries increased risk for the development of hypertension, myocardial infarction, and stroke. The prevailing mechanism felt to underlie the association between OSA and adverse cardiovascular sequellae is heightened sympathetic nervous system activity stemming from repetitive apneic events, although falls in cardiac output that accompany large negative intrathoracic pressure swings, and repetitive hypoxia/reoxygenation associated with oxidative stress and endothelial dysfunction have also been implicated. In contrast to neurologically intact persons, individuals with tetraplegia represent a model of sympathetic denervation characterized by relative bradycardia and low resting blood pressure. It is unknown whether OSA confers increased cardiovascular disease risk in these individuals, although the prevalence of cardiovascular disease and attributable mortality appear to be greater than that encountered in the general population. We suspect that obstructive sleep apnea complicating tetraplegia imposes significant hemodynamic stress due to falls in cardiac output during apneic events not arrested by catecholamine-induced chronotropic, inotropic, and vasopressor effects. Muscle paralysis and blunted hypercapnic ventilatory responsiveness in persons with tetraplegia, which are also normal rapid eye movement (REM) sleep phenomena, could predispose to greater apnea severity and potentiate falls in cardiac output similar to that observed during REM sleep in able-bodied persons, but will likely occur regardless of sleep stage. We also anticipate that falls in cardiac output and renal hypoperfusion will lead to activation of the renin-angiotensin system, the chronic up- regulation of which has been associated with increased cardiovascular mortality. The purpose of this pilot investigation is therefore to determine in a human model of respiratory muscle paralysis and impaired sympathetic cardiovascular control whether persons with tetraplegia diagnosed with OSA manifest greater decreases in cardiac output during apneic events than that witnessed in neurologically intact individuals with OSA. In the context of the acute hemodynamic changes associated with OSA in these two groups, and in comparison to a third group of subjects with tetraplegia without OSA, we will also examine differences in urinary markers of catecholamine release (vanillyl mandelic acid, metanephrines and normetanephrine), and in plasma levels of atrial natriuretic factor, a marker of atrial stretch. A secondary objective of this pilot investigation will be to investigate whether nocturnal plasma renin and serum aldosterone concentrations differ among individuals with tetraplegia and OSA compared to their counterparts without OSA. An exploratory aim will be to determine if hypoxemia stemming from repetitive apneas leads to elevation in markers of vascular inflammation, specifically high sensitivity C-reactive protein and interleukin-6, in individuals with OSA compared to those without OSA.

描述（由申请人提供）： 筛查研究表明，四肢瘫痪患者中重度阻塞性睡眠呼吸暂停（OSA）的患病率为22%至36%，大大超过了一般人群中男性9.1%和女性4%的患病率估计值。最近的证据表明，未经治疗的OSA会增加患高血压、心肌梗死和中风的风险。普遍认为OSA和不良心血管后遗症之间相关性的机制是由重复性呼吸暂停事件引起的交感神经系统活动增强，尽管伴随大的负胸内压波动的心输出量福尔斯下降，以及与氧化应激和内皮功能障碍相关的重复性缺氧/复氧也有牵连。与神经系统完整的人相比，四肢瘫痪的人代表了交感神经失神经支配的模型，其特征在于相对心动过缓和低静息血压。目前尚不清楚OSA是否会增加这些个体的心血管疾病风险，尽管心血管疾病的患病率和归因死亡率似乎高于一般人群。我们怀疑阻塞性睡眠呼吸暂停合并四肢瘫痪会产生显著的血流动力学压力，这是由于在呼吸暂停事件中心输出量的福尔斯下降，而不是由儿茶酚胺诱导的变时性、变力性和血管加压作用引起的。四肢瘫痪患者的肌肉麻痹和高碳酸血症反应迟钝，也是正常的快速眼动（REM）睡眠现象，可能导致呼吸暂停严重程度加重，并增强心输出量的福尔斯下降，类似于在健全人的REM睡眠期间观察到的情况，但无论睡眠阶段如何，都可能发生。我们还预期心输出量的福尔斯下降和肾灌注不足将导致肾素-血管紧张素系统的激活，其慢性上调与心血管死亡率增加相关。因此，本初步研究的目的是确定在呼吸肌麻痹和交感心血管控制受损的人类模型中，诊断为OSA的四肢瘫痪患者在呼吸暂停事件期间的心输出量是否比神经系统完整的OSA患者表现出更大的减少。在这两组与OSA相关的急性血流动力学变化的背景下，并与第三组无OSA的四肢瘫痪受试者进行比较，我们还将检查尿中儿茶酚胺释放标志物（香草扁桃酸，metanephrines和normetanephrine）的差异，以及心房牵张标志物心房利钠因子的血浆水平。本初步研究的次要目的是研究四肢瘫痪合并OSA患者与非OSA患者夜间血浆肾素和血清醛固酮浓度是否存在差异。一个探索性的目的将是确定是否低氧血症引起的反复呼吸暂停血管炎症的标志物，特别是高敏C反应蛋白和白细胞介素-6的升高，在个人与OSA相比，没有OSA。