Automated Abdominal Binder for Orthostatic Hypotension

用于直立性低血压的自动腹部绑带

• 批准号: 10371026
• 负责人: Luis Enrique Okamoto
• 金额: $ 53.97万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10371026
• 关键词: Abdomen; Accelerometer; Acute; Age; Blood Circulation; Blood Pressure; Caregivers; Clinical; Continuous Positive Airway Pressure; Devices; Diuresis; Drops; Elderly; Electric Capacitance; Fostering; Functional disorder; Goals; Hour; Human; Hypertension; Impairment; Incidence; Knee; Manuals; Measures; Medical; Midodrine; Musculoskeletal Equilibrium; Orthostatic Hypotension; Patients; Pharmaceutical Preparations; Pharmacotherapy; Physiologic pulse; Play; Population; Posture; Quality of life; Risk Factors; Role; Splanchnic Circulation; Stroke Volume; Supination; Techniques; Testing; Thigh structure; Venous; arterial stiffness; autonomic reflex; blood pressure control; blood pressure reduction; cardiovascular risk factor; comorbidity; compliance behavior; disability; electric impedance; fall risk; falls; hemodynamics; improved; indexing; insight; mortality; neurogenic orthostatic hypotension; novel; novel strategies; novel therapeutics; positive airway pressure; pressure; public health relevance; standard of care; therapeutically effective; therapy development

PROJECT SUMMARY Neurogenic orthostatic hypotension (nOH) is a significant medical problem in the elderly; It not only causes substantial disability, but is also a regonized risk for falls and increased mortality. The main hemodynamic mechanism underlying the fall in upright blood pressure (BP) in nOH is an exagerated decrease in venous return due to splanchnic venous pooling that patients are unable to compensate for because of impaired autonomic reflexes. Developing therapies that reduce splanchnic capacitance and restore venous return would have the potential to selectively improve upright BP. However, the only approved treatments for nOH are pressor agents which do not target the underlying pathophysiology and increase supine BP as much or more than upright BP. Furthermore, their increase in supine hypertension leads to pressure diuresis and worsening of OH. We have developed an automated abdominal binder that uses a novel technological approach to overcome the limitations of current drug therapy. The device is triggered by an accelerometer that senses the patient's upright posture and inflates to a sustained a servo-controlled compression pressure of 40 mm Hg. The device automatically deflates when the patient is seated or supine and, therefore, will not have the negative effect of supine hypertension inherent to pressor agents. Our preliminary results showed not only that this device acutely improves orthostatic tolerance and upright BP in nOH patients, but also that it is as effective as midodrine, the current standard of care. Thus, this device has several potential advantages over current therapy: it targets the underlying pathophysiology of OH (unrestrained venous pooling), its effects are immediate compared to medications that usually require about an hour to reach peak effect; it is activated only when standing (it does not induce or worsen supine hypertension), and it does not rely on patient compliance or caregiver involvement. The purpose of this project is to investigate the mechanisms by which the automated abdominal binder improves upright BP and orthostatic tolerance in nOH patients, and the effects of abdominal compression on central hemodynamics and markers of cardiovascular risk. We propose 3 proof-of- concept clinical mechanistic studies to 1) test the hypothesis that the automated abdominal binder improves upright BP by decreasing splanchnic capacitance, venous pooling and the orthostatic drop in stroke volume compared to sham device and midodrine; 2) to determine the acute effects of the automated binder and midodrine on markers of cardiovascular risk such as augmentation index, pulse wave velocity and central BP, and 3) to test the hypothesis that the automated abdominal binder will be associated with lower 24-hr supine BP, reduced diuresis and improved upright BP in the morning after treatement compared to daytime use of midodrine (10 mg t.i.d). We believe the results of these studies will provide the mechanistic insight to foster the efforts currently under way to develop a novel therapy for nOH targeting splanchnic capacitance.

项目摘要 神经源性体性低血压（NOH）是老年人的重大医学问题。它不仅导致 实质性残疾，但也是跌倒和死亡率增加的重建风险。主要的血液动力学 NOH中直立血压下降（BP）的基础机制是静脉回流的降低 由于自主神经受损而无法补偿患者无法补偿 反射。开发降低诊断电容和恢复静脉回流的疗法将具有 有选择地改善直立的BP的潜力。但是，NOH的唯一批准治疗方法是施加代理人 不针对潜在的病理生理学，并增加仰卧BP的量超过直立的BP。 此外，它们的仰卧高压升高会导致diuresis压力和OH的恶化。 我们已经开发了一种自动化的腹部粘合剂，该腹部粘合剂使用一种新型的技术方法来克服 当前药物治疗的局限性。该设备是由感知患者的加速度计触发的 直立的姿势并膨胀至持续的伺服控制压缩压力为40 mm Hg。设备 自动在患者坐下或仰卧时自动放气，因此不会产生 仰卧为施加剂固有的高血压。我们的初步结果不仅表明该设备敏锐 改善NOH患者的体位耐受性和直立的BP，但它与中脊一样有效， 当前的护理标准。因此，该设备比当前疗法具有多个潜在的优势：它针对 OH的潜在病理生理学（不受约束的静脉合并），其作用是直接的 通常需要大约一个小时才能达到峰值效应的药物；仅在站立时才激活 不诱导或恶化仰卧高血压），并且不依赖于患者的合规性或护理人员的参与。 该项目的目的是研究自动化腹部的机制 粘合剂改善了NOH患者的直立BP和体位耐受性，腹部的影响 对中央血流动力学和心血管风险标记的压缩。我们提出了3个证明 概念临床机理研究1）检验以下假设：自动腹部粘合剂改善 通过降低鼻子电容，静脉池和中风量的体位降低，直立bp。 与假装置和中脊相比； 2）确定自动粘合剂的急性影响和 心血管风险标志物上的中脊，例如增强指数，脉搏波速度和中央BP， 3）检验以下假设：自动化腹部粘合剂将与较低的24小时仰卧BP有关 与白天使用中端相比 （10毫克T.I.D）。我们认为这些研究的结果将提供机械洞察力，以促进努力 目前正在开发一种针对新型诊断电容的新型疗法。