Automated Abdominal Binder for Orthostatic Hypotension

项目总结 神经源性直立性低血压(NOH)是老年人的一个重大医学问题；它不仅导致 严重的残疾，但也是跌倒和死亡率增加的合理风险。主要血流动力学 NOH患者直立血压(BP)下降的机制是静脉回流过度减少 由于自主神经受损而患者无法补偿的内脏静脉淤积 条件反射。开发减少内脏电容和恢复静脉回流的治疗方法将具有 有选择地改善直立式BP的潜力。然而，唯一被批准的治疗NOH的药物是升压剂。 这不针对潜在的病理生理学，并增加仰卧位血压与直立血压一样多或更多。 此外，它们在仰卧位高血压中的增加导致压力利尿和OH的恶化。 我们已经开发了一种自动腹部粘合剂，它使用了一种新的技术方法来克服 当前药物治疗的局限性。该设备是由一个加速计触发的，它可以感知患者的 直立姿势，充气至持续的伺服控制压缩压力为40毫米汞柱。该设备 当病人坐着或仰卧时会自动放气，因此不会有 升压剂所固有的仰卧位高血压。我们的初步结果表明，这个装置不仅敏锐地 改善NOH患者的立位耐力和直立血压，但它也与米多君一样有效， 目前的护理标准。因此，这种设备比目前的治疗方法有几个潜在的优势：它针对的是 ··· 通常需要大约一个小时才能达到最佳效果的药物；只有在站立时才会激活(确实如此 不会导致或加重仰卧位高血压)，而且它不依赖于患者依从性或护理人员的参与。 这个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，以及腹水的影响 压迫对中枢血流动力学和心血管风险标志物的影响。我们提出了3个证明 概念临床机制研究，以1)检验自动腹部粘合剂改善的假设 通过减少内脏电容、静脉充血和直立性每搏输出量下降来实现直立血压 与Sham装置和米多君比较；2)确定自动粘结剂的急性影响和 米多君对心血管危险指标如增大指数、脉搏波速度和中枢血压的影响 以及3)为了检验自动腹部绑定器将与较低的24小时仰卧位血压相关的假设， 与白天使用米多君相比，治疗后早晨利尿减少，直立血压改善 (10 mg，ti.d)。我们相信，这些研究的结果将为促进这些努力提供机械性的见解。 目前正在开发一种针对内脏电容的新型NOH治疗方法。

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.