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: 7872572
• 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: 2010-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7872572
• 关键词: Acids; Acute; Age; Aldosterone; American; Angiotensin II; Apnea; Arousal; Atherosclerosis; Atrial Natriuretic Factor; Blood Pressure; Body Surface Area; Bradycardia; C-reactive protein; Cardiac; Cardiac Output; Cardiovascular Diseases; Cardiovascular system; Catecholamines; Chemoreceptors; Chronic; Consensus; Control Groups; Data; Development; Diagnosis; Disease Progression; Down-Regulation; Epidemiologic Studies; Event; Fostering; Functional disorder; General Population; Generations; Goals; Heart Atrium; Heart Rate; High Prevalence; Hormonal Change; Hour; Human; Hypertension; Hypoxemia; Hypoxia; Individual; Injury; Interleukin-6; Interruption; Investigation; Kidney; Knowledge; Lead; Link; Maintenance; Measures; Mediating; Medical; Metanephrine; Mission; Modeling; Muscle; Myocardial Infarction; Myocardial Ischemia; Nerve; Obstructive Sleep Apnea; Oxidative Stress; Paralysed; Patient Care; Persons; Pilot Projects; Plasma; Polysomnography; Population; Population Statistics; Prevalence; Pulse Oximetry; Quadriplegia; Quality of life; REM Sleep; Relative (related person); Renin; Renin-Angiotensin System; Renin-Angiotensin-Aldosterone System; Reporting; Research Design; Respiratory Paralysis; Rest; Risk; Risk Factors; Screening procedure; Serum; Severities; Sleep; Sleep Apnea Syndromes; Sleep Stages; Spinal cord injury; Stress; Stretching; Stroke; Stroke Volume; Surrogate Markers; Sympathectomy; Sympathetic Nervous System; Symptoms; System; Time; Treatment Efficacy; Up-Regulation; Vasoconstrictor Agents; Veterans; Woman; Work; atherogenesis; attributable mortality; base; cardiovascular disorder risk; chronotropic; cytokine; falls; hemodynamics; improved; indexing; men; middle age; mortality; non rapid eye movement; pressure; public health relevance; response; rib bone structure; 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. PUBLIC HEALTH RELEVANCE: Relevance of the Proposed Work to the VA Patient Care Mission Fostering a better understanding of the common medical conditions that beset veterans with SCI and how best to treat them, with the ultimate goal of improving quality of life for these individuals is highly relevant to the VA Patient Care Mission. Investigation of the acute cardiovascular events associated with repetitive obstructive apneas during sleep in persons with tetraplegia is a necessary first step toward gaining an understanding of the hemodynamic and potentially deleterious consequences of OSA in this population. Subsequent investigations based upon preliminary data from this pilot investigation, forming the basis for a full Merit Review, would be geared toward expanding upon initial observations and evaluating treatment effects, of which little is known [10, 35, 79, 79].

描述（由申请人提供）： 筛查研究表明，四肢瘫痪患者中度至重度阻塞性睡眠呼吸暂停 (OSA) 的患病率在 22% 至 36% 之间，大大超过一般人群中男性 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、心肌梗塞和中风的风险。 OSA 与不良心血管后遗症之间关联的普遍机制是重复性呼吸暂停事件引起的交感神经系统活动增强，尽管伴随胸腔内压力大幅负波动导致的心输出量下降，以及与氧化应激和内皮功能障碍相关的重复性缺氧/复氧也与此有关。与神经系统完好的人相比，四肢瘫痪的人代表了交感神经去神经支配的模型，其特征是相对心动过缓和低静息血压。尽管心血管疾病的患病率和死亡率似乎高于一般人群，但 OSA 是否会增加这些人的心血管疾病风险尚不清楚。我们怀疑，并发四肢瘫痪的阻塞性睡眠呼吸暂停会造成显着的血流动力学压力，因为呼吸暂停事件期间心输出量下降，而儿茶酚胺诱导的变时性、正性肌力和血管加压作用无法阻止这一情况。四肢瘫痪患者的肌肉麻痹和高碳酸血症通气反应迟钝，这也是正常的快速眼动 (REM) 睡眠现象，可能会导致更严重的呼吸暂停，并导致心输出量下降，类似于身体健全的人在快速眼动睡眠期间观察到的情况，但无论睡眠阶段如何，都可能发生。我们还预计心输出量下降和肾脏灌注不足将导致肾素-血管紧张素系统激活，该系统的长期上调与心血管死亡率增加有关。因此，这项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体模型中，诊断为 OSA 的四肢瘫痪患者在呼吸暂停事件期间是否表现出比神经系统完好的 OSA 患者更大的心输出量下降。在这两组中与 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，我们还将检查儿茶酚胺释放的尿标志物（香草扁桃酸、变肾上腺素和去甲变肾上腺素）的差异，以及心房钠尿因子（心房舒张标志物）血浆水平的差异。这项试点研究的第二个目标是调查患有四肢瘫痪和 OSA 的个体与没有 OSA 的个体相比，夜间血浆肾素和血清醛固酮浓度是否存在差异。一项探索性目标是确定患有 OSA 的个体与没有 OSA 的个体相比，重复性呼吸暂停引起的低氧血症是否会导致血管炎症标志物升高，特别是高敏 C 反应蛋白和白细胞介素 6。 公共卫生相关性： 拟议工作与 VA 患者护理使命的相关性 更好地了解困扰 SCI 退伍军人的常见医疗状况以及如何最好地治疗这些疾病，最终目标是改善这些人的生活质量，与 VA 患者护理使命高度相关。对四肢瘫痪患者睡眠期间重复性阻塞性呼吸暂停相关的急性心血管事件进行调查，是了解该人群中 OSA 的血流动力学和潜在有害后果的必要的第一步。基于该试点调查的初步数据的后续调查构成了全面的优点审查的基础，将旨在扩大初步观察并评估治疗效果，而对此知之甚少[10,35,79,79]。