Bionic Baroreflex System for Blood Pressure Control

描述（由申请人提供）：多系统萎缩患者 (MSA)，一种散发性和进行性神经退行性疾病， 直立性低血压、餐后低血压和仰卧位高血压。 低血压通常在站立后数秒内引起晕厥前症状， 需要患者坐着或躺下以防止晕厥。仰卧位高血压 通过过度夜间利尿降低睡眠质量，并导致 夜间血容量损失，这加重了直立性低血压 白天的需要新的治疗策略， 考虑到这种高血压和低血压之间的循环。 我们实验室最近的研究得出了意想不到的观察结果， 交感神经活动存在于MSA中，但不受正常控制 机制等这种交感神经活动产生不适当的仰卧 高血压，但不能预防深度体位性低血压。 MSA中残留交感神经活性的鉴定具有重要意义 对新治疗方法的影响。我们假设一个仿生人 基于硬膜外电刺激的压力反射系统将有助于 由血管中枢取代交感神经活动的缺失控制。 动物实验的初步数据显示， 在直立性压力下。这项拨款建议的目的是寻找 为MSA患者提供一种有效实用的仿生压力感受器反射系统， 压力反射衰竭首先，我们将开发一个原型仿生压力感受器反射 控制系统使用压力反射去神经大鼠。然后，系统将 应用于人工控制，肌肉交感神经活动， 已经有硬膜外电刺激器的患者， 控制慢性疼痛。II期研究将涉及动物研究， 在患有MSA的患者中，以确定仿生 压力反射系统改善血压控制。

DESCRIPTION (provided by applicant): Patients with multiple system atrophy (MSA), a sporadic and progressive neurodegenerative disorder, suffer from orthostatic hypotension, postprandial hypotension and supine hypertension. Hypotension causes presyncopal symptoms usually within seconds of standing and requires the patient to sit or lie down to prevent syncope. Supine hypertension reduces sleep quality through excessive nocturnal diuresis, and results in blood volume loss during the night, which aggravates orthostatic hypotension during the day. New strategies of treatments are required which take into account this cycling between hypertension and hypotension. Recent studies in our laboratory have yielded the unexpected observation that sympathetic activity is present in MSA, but is not subject to normal control mechanisms. This sympathetic activity produces inappropriate supine hypertension, but is not able to prevent the profound orthostatic hypotension. The identification of residual sympathetic activity in MSA has important implications for new therapeutic approaches. We hypothesize that a bionic baroreflex system based on electrical epidural spinal stimulation will help to replace the missing control of sympathetic activity by the vasomotor center. Preliminary data in animals showed that such a system maintained blood pressure during orthostatic stress. The purpose of this grant proposal is to search for an effective and practical bionic baroreflex system for patients with MSA and baroreflex failure. First, we will develop a prototype bionic baroreflex control system using baroreflex-denervated rats. Then, the system will be applied to control artificially, the muscle sympathetic nerve activity in patients who already have an epidural electrical stimulator in place for the control of chronic pain. A Phase II study would involve studies in animals and in patients with MSA to determine the long-term efficacy of the bionic baroreflex system in improving blood pressure control.