Bionic Baroreflex System for Blood Pressure Control

描述(申请人提供)：多系统萎缩患者 (MSA)是一种散发性和进行性神经退行性疾病，患有 体位性低血压、餐后低血压和仰卧位高血压。 低血压通常在站立后几秒钟内引起突触前症状 要求病人坐着或躺下以防止晕厥。仰卧位高血压 夜间利尿过多会降低睡眠质量，并导致 夜间失血，加重直立性低血压 在白天。需要新的治疗策略，以考虑到 考虑到高血压和低血压之间的循环。 我们实验室最近的研究发现了意想不到的现象 交感神经活动存在于MSA中，但不受正常控制 机械装置。这种交感神经活动会产生不适当的仰卧。 高血压，但不能预防深度直立性低血压。 MSA中残留交感神经活性的鉴定具有重要意义 对新的治疗方法的影响。我们假设一个仿生体 基于硬膜外脊髓电刺激的压力反射系统将有助于 血管运动中枢取代了交感神经活动的缺失控制。 在动物身上的初步数据显示，这样的系统维持血压 在立位应激期间。这项拨款提案的目的是为了寻找 一种有效实用的MSA和MSA患者的仿生压力反射系统 压力感受器反射衰竭。首先，我们将开发一个仿生压力反射的原型。 压力感受性反射去神经大鼠的控制系统。然后，系统将被 应用于人工控制，肌交感神经活动 已经安装了硬膜外电刺激器的患者 控制慢性疼痛。第二阶段的研究将包括对动物和 在MSA患者中确定仿生剂的远期疗效 压力反射系统在改善血压控制中的作用。

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.