Hemodynamic Effects of Positive Airway Pressure to Treat Supine Hypertension and Improve Neurogenic Orthostatic Hypotension

气道正压通气治疗仰卧位高血压和改善神经源性直立性低血压的血流动力学效应

• 批准号: 10532156
• 负责人: Italo Biaggioni
• 金额: $ 67.16万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-01 至 2026-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10532156
• 关键词: Abdomen; Acute; Blood Pressure; Buffers; Cardiac Output; Cardiovascular system; Chest; Clinical; Continuous Positive Airway Pressure; Diuresis; Elderly; Electric Capacitance; Exclusion; Failure; Fright; Goals; Head; Hormones; Hypertension; Impairment; Knowledge; Masks; Multiple System Atrophy; Natriuresis; Nerve Degeneration; Nocturia; Nocturnal Hypertension; Obstructive Sleep Apnea; Organ; Orthostatic Hypotension; Outcome; Output; Parkinson Disease; Patients; Positioning Attribute; Pure Autonomic Failures; Quality of life; Regulation; Risk; Risk Factors; Sleep; Sleep disturbances; Splanchnic Circulation; Stroke Volume; Supination; Testing; Trimethaphan; Venous; Weight; arterial stiffness; autonomic reflex; clinically significant; comorbidity; disability; effective therapy; fall risk; falls; hemodynamics; improved; indexing; innovation; insight; mortality; neurogenic orthostatic hypotension; novel; novel strategies; novel therapeutic intervention; patient population; positive airway pressure; pressure; public health relevance; urinary

Orthostatic hypotension (OH) is a common disabling condition in the elderly, particularly in those with impaired autonomic reflexes. Supine hypertension is the most common comorbidity; it not only increases the risk for target organ damage but also induces pressure natriuresis during nighttime causing nocturia and volume depletion that contributes to OH. Thus, nocturnal hypertension worsens daytime OH. Unfortunately, there is reluctance to treat supine hypertension for fear of worsening OH. Sleeping in a head-up tilt (HUT) position can improve nocturnal hypertension by reducing venous return, stroke volume and cardiac output, but tilt levels needed to produce these effects are difficult to achieve clinically. In this application, we propose that increasing intrathoracic pressure with continuous positive airway pressure (CPAP), at levels used clinically, will produce similar hemodynamic effects as HUT, by inducing venous pooling into the splanchnic circulation. Indeed, our preliminary studies show that CPAP, at levels used clinically, induces an acute and reversible decrease in blood pressure in autonomic failure patients without obstructive sleep apnea (OSA) by a direct hemodynamic mechanism, and this effect is sustained during the night and associated with decreased nocturia. In normal subjects this effect is masked by compensatory sympathetic activation. The overall goal of this application is to test the hypothesis that increasing intrathoracic pressure with CPAP is an effective treatment for nocturnal hypertension in patients with autonomic failure and that, by reducing pressure diuresis, it will improve daytime OH. In Specific Aim 1, we will characterize the hemodynamic mechanisms of CPAP in autonomic failure patients, determine its effects on volume shifts from the thoracic to abdominal segments, on hormones that regulate natriuresis, and on central blood pressure and indices of arterial stiffness. These indices are better predictors of negative cardiovascular outcomes than brachial blood pressure, and this unique patient population will allow us to determine the effects of CPAP unencumbered by sympathetic modulation. We also propose overnight proof-of-concept studies to test the hypotheses that CPAP is effective in controlling nocturnal supine hypertension (Specific Aim 2) and reduces nighttime diuresis, resulting in improvement of daytime orthostatic tolerance (Specific Aim 3). For these initial proof-of-concept mechanistic studies we exclude patients with OSA because our focus is on the novel hemodynamic effects of CPAP rather than suppression of apneic episodes. We believe the proposed studies will lead to a clinically significant and innovative approach for the management of nocturnal hypertension in patients with autonomic failure, changing the way we manage patients, and eliminating the controversy of whether to treat, or not to treat, supine hypertension. If successful, lowering nighttime blood pressure will reduce nocturia, which not only impairs sleep but also exposes patients to falls. More importantly, it will improve daytime orthostatic tolerance and improve the quality of life of our patients. Our studies will also improve our basic knowledge about the effects of CPAP on cardiovascular regulation, that can then be applied to other conditions.

体位性低血压（OH）是老年人的常见残疾状况，特别是在患有受损的人中 自主反射。仰卧高血压是最常见的合并症。它不仅增加了目标的风险 器官损坏，但还会在夜间诱导压力纳地尿症，从而导致夜尿和体积耗竭 有助于哦。因此，夜间高血压使白天哦。不幸的是，不愿 治疗仰卧高血压，因为担心哦。在头部倾斜（小屋）位置睡觉可以改善 夜间高血压通过减少静脉回流，中风量和心脏输出，但需要倾斜水平 产生这些影响很难在临床上实现。在此应用程序中，我们建议增加静脉曲制 在临床上使用的水平下，具有连续正气道压力（CPAP）的压力将产生相似的 血液动力学作用是小屋，通过诱导静脉聚集到斑点循环中。确实，我们的初步 研究表明，在临床上使用的水平上，CPAP诱导血压急性和可逆降低 在没有阻塞性睡眠呼吸暂停（OSA）的自主衰竭患者中 这种效果在夜间持续，并与夜尿降低有关。在正常受试者中，这种影响是 由代偿性交感神经激活掩盖。该应用的总体目标是检验假设 CPAP胸前压力增加是患者夜间高血压的有效治疗方法 随着自主性失败，通过降低压力利尿，它将改善白天OH。在特定的目标1中， 我们将表征自主衰竭患者CPAP的血液动力学机制，确定其影响 在体积从胸腔到腹部片段，调节纳地雷氏菌的激素和中央 血压和动脉刚度的指标。这些指数是负心血管的更好预测指标 结局比肱臂血压，这一独特的患者人群将使我们能够确定影响 CPAP不受交感神经调节的束缚。我们还提出了夜间概念证明研究以测试 CPAP有效控制夜间仰卧高压（特定目标2）并减少的假设是 夜间利尿，导致白天的体位容忍度改善（特定目标3）。对于这些最初 概念证明的机理研究我们排除了OSA患者，因为我们的重点是新颖 CPAP的血液动力学作用而不是抑制呼吸暂停发作。我们相信拟议的研究 将导致一种具有临床意义和创新的方法来管理夜间高血压 自主失败的患者改变了我们管理患者的方式，并消除了争议 是否治疗或不治疗仰卧高血压。如果成功，降低夜间血压将减少 夜尿，不仅会损害睡眠，还会使患者暴露于跌倒。更重要的是，它将改善白天 体位耐受性并改善患者的生活质量。我们的研究也将改善我们的基本 有关CPAP对心血管调节的影响的知识，然后可以应用于其他条件。