Investigation of Partial Electrical Nerve Block for Autonomic Regulation

自主调节部分电神经阻滞的研究

• 批准号: 10323259
• 负责人: Tina Louise Vrabec
• 金额: $ 46.06万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-06 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10323259
• 关键词: Abdomen; Acute; Area; Arrhythmia; Autonomic Nerve Block; Axon; Bilateral; Biosensor; Blood Vessels; Cardiac; Cardiac Myocytes; Cardiac ablation; Cardiovascular Diseases; Catecholamines; Characteristics; Chest; Chronic; Coronary heart disease; Data; Decentralization; Development; Disease; Down-Regulation; Effectiveness; Elements; Evaluation; Excision; Feedback; Ganglia; Goals; Heart; Heart Diseases; Heart Rate; Heart failure; Hyperalgesia; Hyperhidrosis disorder; Implantable Defibrillators; Individual; Intervention; Investigation; Ischemia; Laboratories; Lead; Manuals; Modality; Monitor; Myocardial dysfunction; Nerve; Nerve Block; Neurotransmitters; Norepinephrine; Operative Surgical Procedures; Outcome; Pathology; Pathway interactions; Patients; Periodicity; Peripheral; Persons; Pharmaceutical Preparations; Property; Reaction Time; Reading; Recovery; Reflex action; Regulation; Rodent Model; Scanning; Source; Specific qualifier value; Stress; Sympathetic Nerve Block; System; Tachyarrhythmias; Techniques; Therapeutic; Time; Tissues; United States; Ventricular; Work; autonomic nerve; autonomic reflex; base; cardiogenesis; clinically relevant; conventional therapy; density; effective therapy; electric field; heart function; indexing; innovation; interstitial; neuroregulation; novel; porcine model; response; side effect; sudden cardiac death; technique development; temporal measurement

Investigation of Partial Electrical Nerve Block for Autonomic Regulation More than 600,000 people die of heart disease in the United States every year. Sudden cardiac death often occurs as a result of ventricular tachyarrhythmias (VT) in patients with coronary heart disease (CHD) and/or heart failure (HF). Autonomic dysregulation following cardiac pathology is essential to the development of HF and VT. Existing interventions are lacking in response time, reversibility, and adaptability over time. Thus, a major unmet need is to impact/regulate sympathetic neural control of cardiac function using a targeted, rapid, reversible, and gradable modality that is safe for autonomic nerves and, ultimately, can be deployed chronically. Over the last decade, advances in the field of electrical nerve block, has shown promise to be this desired therapeutic modality. Peripheral electrical nerve block has a rapid onset, is reversible and gradable. Previously nerve block has been used to completely block a nerve. This is the first study to explore the value of partially blocking a nerve. Partial electrical nerve block can mitigate autonomic reflexes without extinguishing them. However, the stability and controllability of the block at any desired level are currently unknown. Understanding the characteristics of partial block would result in far reaching contributions to the control of autonomic systems. The feasibility of closed loop control of cardiac function is highly dependent on the availability of real time feedback of autonomic parameters. Existing monitoring techniques are lacking in both responsiveness and sensitivity. To provide a real-time control source, direct recording of autonomic nerve function will be performed using real-time measurements of cardiac interstitial and vascular catecholamines. The central hypothesis of this proposal is that the autonomic system can be down regulated and the sympathetic drive to the heart maintained at a clinically relevant lower set point using DC block. The ability to maintain the autonomic system at varying specified set points based on changing cardiac function and indices of cardiac stress (e.g VT burden, heart rate) would allow for highly patient specific disease interventions. Specifically, for this proposal, the goal is to regulate functional sympathetic control of the heart and maintain a given set point for 30 minutes. Aim 1: Identify and characterize the parameters of partial nerve block needed to maintain nerve block at a given set point using an acute rodent model on the vagus (autonomic) nerve. Aim 2: Identify nerve block targets in the cardiac sympathetic pathway and characterize the effect of partial block on evoked sympathetic reflex responses, in particular the effect on block efficacy and recovery. Aim 3: Evaluate the effect of partial block on regional cardiac norepinephrine using release fast scanning cyclic voltammetry in coordination with high density assessments of regional cardiac electrical function. Aim 4: Using the neurotransmitter biosensor, develop a control paradigm to determine both when to initiate block as well as determining the block level.

研究部分电神经块的自主法规 每年美国有超过60万人死于心脏病。突然心脏死亡 通常是由于心脏病患者（CHD）和/或 心力衰竭（HF）。心脏病理后的自主性失调对于HF的发展至关重要 和VT。随着时间的推移，缺乏响应时间，可逆性和适应性的现有干预措施。因此， 主要的未满足需要是使用目标，快速， 对自主神经安全，最终可以长期部署的自主神经安全的可逆和渐变方式。 在过去的十年中，电神经阻滞领域的进步已显示出希望 治疗方式。外围电神经阻滞具有快速发作，可逆且可分析。之前 神经阻滞已被用来完全阻断神经。这是探索部分价值的第一项研究 阻止神经。部分电神经阻滞可以减轻自主反射而不会熄灭它们。 但是，目前尚不清楚块在任何所需级别上的稳定性和可控性。理解 部分阻滞的特征将导致对自主系统控制的贡献。 心脏功能的闭环控制的可行性高度取决于实时的可用性 自主参数的反馈。现有的监测技术都缺乏响应能力和 灵敏度。为了提供实时控制源，将执行自主神经功能的直接记录 使用心脏间隙和血管儿茶酚胺的实时测量。中心假设 提议是自主系统可以被调节，并保持对心脏的同情驱动 在临床相关的下部设定点，使用直流块。维护自主系统时的能力 指定的设定点基于不断变化的心脏功能和心脏应力指数（例如VT负担，心率） 将允许高度患者特定的疾病干预措施。具体而言，对于此提案，目标是规范 对心脏的功能交感控制并保持给定的设定点30分钟。目标1：识别和 表征使用一个通过一个 迷走神经（自主）神经上的急性啮齿动物模型。目标2：确定心脏中的神经阻滞靶标 交感神经途径并表征部分阻滞对唤起的交感反射反应的影响， 尤其对块功效和恢复的影响。目标3：评估部分阻滞对区域心脏的影响 使用快速扫描循环伏安法的去甲肾上腺素，并在高密度评估的协调中 区域心电功能。目标4：使用神经递质生物传感器，将控制范式发展为 确定何时启动块以及确定块级别。