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，四半症患者的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，因此，男性的患病率估计值大大超过了9.1％的患病率估计值，而在普通人群中遇到的女性中的患病率估计为4％。最近的证据表明，未经治疗的OSA带来了增加高血压，心肌梗塞和中风的风险。尽管心脏输出的落下，但伴随着大型负负压力波动的心脏输出落下，而反复的呼吸暂停性伴随着重复性的呼吸暂停事件，但人们认为，OSA与心血管不良后遗症之间的关联是基础的流行机制。与神经学完整的人相反，四边形的个体代表了一种交感神经的模型，其特征是相对心动过缓和低静止血压。尽管心血管疾病的流行和可归因的死亡率似乎比普通人群中遇到的患病率更大，但OSA是否同意这些人的心血管疾病风险是否增加。我们怀疑四脑肾上腺新症并发阻塞性睡眠呼吸暂停会在呼吸暂停事件中降低心脏输出引起的明显的血液动力学应激，而没有被儿茶酚胺诱导的表现，肌瘤，肌核和加压剂效应。肌肉瘫痪和肌肉瘫痪的四脑血以及正常的快速眼动（REM）睡眠现象的人的肌肉瘫痪和肌肉瘫痪，可能会倾向于更大的呼吸暂停严重程度，并且在有能力的人的REM睡眠期间观察到的心脏输出中会增强心脏输出，但可能会发生睡眠阶段。我们还预计，心脏输出和肾脏灌注不足会导致肾素 - 血管紧张素系统的激活，肾素 - 血管紧张素系统的慢性调节与心血管死亡率的增加有关。因此，该试验研究的目的是在人类的呼吸肌瘫痪模型中确定和交感神经性心血管控制障碍，诊断为诊断出患有OSA的四边形的人在呼吸暂停事件中是否表现出比神经系统完整的OSA见证的呼吸暂停事件中的心脏输出降低。在这两组中与OSA相关的急性血液动力学变化的背景下，以及与无OSA无四脑性的第三组受试者相比，我们还将检查Catecholamine释放的尿标志物（Vanillylylyly candelic酸，元甲基甲基甲甲基和Normetanephrine和NormetAnephrine），以及在静脉内的含量natrial natriartrialtriratirater artertrirater，该试点研究的次要目标是研究四磷酸根和OSA的个体与没有OSA的夜间血浆肾素和血清醛固酮浓度是否有所不同。探索性的目的是确定与没有OSA相比，OSA患者的血管炎症标志物，特别是高灵敏度C反应蛋白和白介素-6是否导致血管炎症标记的升高是否导致升高。 公共卫生相关性： 拟议的工作与VA患者护理任务的相关性促进了对与SCI的退伍军人的共同医疗状况以及如何最好地对待他们的常见医疗状况，其最终目标是改善这些人的生活质量，与VA患者护理任务高度相关。对四肢瘫痪者睡眠期间与重复阻塞性呼吸暂停相关的急性心血管事件的研究是了解该人群中OSA的血液动力学和潜在有害后果的必要第一步。随后的研究基于该试点研究的初步数据，构成了全面优点审查的基础，将旨在扩大最初的观察和评估治疗效果，对此鲜为人知[10，35，79，79]。