Automated Abdominal Binder for Orthostatic Hypotension

项目摘要 神经源性直立性低血压（nOH）是老年人的一个重要医学问题;它不仅导致 严重残疾，但也是福尔斯和死亡率增加的公认风险。主要血流动力学 nOH患者直立位血压（BP）下降的潜在机制是静脉回流的急剧减少 由于内脏静脉淤积，患者由于自主神经受损而无法代偿 反射开发减少内脏电容和恢复静脉回流的疗法将具有 选择性改善直立血压的潜力。然而，唯一批准的nOH治疗是升压剂 其不针对潜在的病理生理学并且使仰卧BP增加与直立BP一样多或更多。 此外，仰卧位高血压的增加导致压力利尿和OH恶化。 我们已经开发出一种自动化的腹带，它使用一种新的技术方法来克服 目前药物治疗的局限性。该设备由一个加速计触发， 直立姿势，并充气至40 mm Hg的持续伺服控制压缩压力。设备 当患者坐着或仰卧时自动放气，因此不会产生 升压药固有的仰卧位高血压。我们的初步结果表明，这种装置不仅可以 改善nOH患者的立位耐受性和直立血压，但也与米多君一样有效， 目前的护理标准。因此，该装置相对于当前疗法具有几个潜在的优点： OH的潜在病理生理学（不受限制的静脉汇集），与 通常需要大约一个小时才能达到峰值效果的药物;它只在站立时激活（它确实 不会诱发或加重仰卧位高血压），并且不依赖于患者的依从性或护理人员的参与。 本项目的目的是研究自动腹部手术的机制， binder改善nOH患者的直立血压和立位耐力，腹部 压迫对中枢血流动力学和心血管风险标志物的影响。我们提出3个证明- 概念临床机制研究，以1）测试自动腹带改善的假设 通过降低内脏电容、静脉汇集和立位每搏输出量下降来降低直立血压 与假器械和米多君相比; 2）确定自动化粘合剂的急性作用， 米多君对心血管风险标志物的影响，如增强指数、脉搏波速度和中心血压， 以及3）检验自动腹部束带与较低的24小时仰卧位BP相关的假设， 与白天使用米多君相比， (10 mg t.i.d）。我们相信，这些研究的结果将提供机制的见解，以促进努力 目前正在开发一种新的治疗nOH靶向内脏电容。

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.