Subcutaneous nerve stimulation for arrhythmia control.

皮下神经刺激可控制心律失常。

• 批准号: 9405146
• 负责人: PENG-SHENG CHEN
• 金额: $ 67.65万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9405146
• 关键词: Ablation; Adverse effects; Arrhythmia; Atrial Fibrillation; Bladder Control; Canis familiaris; Cardiac; Cardiac ablation; Chest; Chronic; Clinical; Clinical Research; Clinical Trials; Coupled; Data; Developed Countries; Developing Countries; Devices; Drug usage; Electric Stimulation; Electrodes; FDA approved; Galvanic Skin Response; Goals; Heart Atrium; Heart Diseases; Human; Label; Left; Letters; Medical; Methods; Modeling; Morbidity - disease rate; Neck; Nerve; Nerve Fibers; Operative Surgical Procedures; Output; Pacemakers; Pain management; Patients; Pharmaceutical Preparations; Procedures; Public Health; Refractory; Research Project Grants; Site; Skin; Structure; Structure of stellate ganglion; Surface; System; Tachyarrhythmias; Testing; Therapeutic; Translating; Ventricular; atrioventricular node; histological studies; implantable device; implantation; mortality; neuroregulation; new technology; preclinical study; response; subcutaneous; transcutaneous stimulation; vagus nerve stimulation; voltage

The specific goal of this research project is to test the hypothesis that the Medtronic InterStim II Neurostimulator coupled with 3889 SNS Leads can be used for subcutaneous nerve stimulation (SCNS) to achieve rhythm and rate control of atrial fibrillation (AF) in a canine model. If the canine studies are successful, we will perform pilot clinical trials to facilitate rate control in patients with AF and rapid ventricular responses. The ultimate goal is to motivate Medtronic Inc. to perform additional clinical studies for FDA approval of SCNS as a labeled indication for managing AF. The study is responsive to the RFA-RM-16-027 because it will utilize existing market-approved technology for new market indications. AF is the most common cardiac arrhythmias in developed countries, and is associated with significantly increased mortality and morbidity. Drugs used for rate and rhythm control of AF are not uniformly successful and may be associated with significant side effects. Catheter ablation of the atrioventricular (AV) node is an option for rate control in patients with drug-refractory AF and rapid ventricular responses. However, AV node ablation makes the patient pacemaker dependent. It is highly desirable to develop an alternative method for AF control without the use drugs or ablation procedures. Histological studies showed that skin is well innervated by sympathetic nerves. In dogs, the postganglionic sympathetic nerve fibers of neck and thorax come primarily from the stellate ganglion (SG). Our preliminary studies showed that subcutaneous nerve stimulation (SCNS) from different sites in the thorax can damage SG and reduce SG nerve activity (SGNA). These findings suggest an exciting possibility that electrical stimulation of the skin may reduce SGNA to provide both rate and rhythm control of AF. Medtronic Inc. has a number of neurostimulators approved by FDA for pain and urinary control. The purpose of the present study was to test the hypothesis that the InterStim II Neurostimulator and the 3889 SNS Leads can be used effectively for SCNS and control AF. If the results are promising, it is possible to motivate Medtronic to sponsor pilot clinical studies and translate these findings to human patients. We propose the following specific aims: Specific Aim 1: To perform SCNS at various outputs to test the hypotheses that the magnitudes of output is important in determining the effects of neuromodulation. Specifically, high output stimulation causes SG damage and reduce sympathetic tone while very low output SCNS can cause SG and cardiac nerve sprouting, thus increasing the sympathetic tone. Specific Aim 2: To test the hypothesis that SCNS at high output is effective in rate and rhythm control of AF while at very low output is proarrhythmic. If SG damage underlies the mechanisms of the antiarrhythmic effects of SCNS, then it follows that high output SCNS is both necessary and sufficient to generate antiarrhythmic effects. On the other hand, if very low output SCNS causes nerve sprouting and increases sympathetic tone, then low output stimulation should be proarrhythmic. We will use a canine model of paroxysmal and persistent AF to test these hypotheses.

该研究项目的具体目标是检验Medtronic Interstim II的假设 神经刺激剂与3889个SNS铅可用于皮下神经刺激（SCN） 在犬模型中实现心房颤动（AF）的节奏和速率控制。如果犬研究成功， 我们将进行试验临床试验，以促进患有AF和快速心室反应患者的速率控制。 最终目标是激励Medtronic Inc.进行其他临床研究以批准SCN 作为管理AF的标记指示。该研究对RFA-RM-16-027的响应敏感，因为它将使用 现有的市场批准技术用于新的市场指示。 AF是最常见的心律不齐 在发达国家，与死亡率和发病率显着提高有关。用于使用的药物 AF的速率和节奏控制并不统一，并且可能与重大副作用有关。 室内（AV）节点的导管消融是药物难治性患者速率控制的一种选择 AF和快速心室反应。但是，AV节点消融使患者起搏器依赖。这是 非常需要开发一种不使用药物或消融程序的AF控制的替代方法。 组织学研究表明，皮肤是通过交感神经来很好地支配的。在狗中，后gionicic 颈部和胸腔的交感神经纤维主要来自星状神经节（SG）。我们的初步 研究表明，来自胸腔不同部位的皮下神经刺激（SCN）会损害SG 并减少SG神经活性（SGNA）。这些发现表明了电刺激的一种令人兴奋的可能性 皮肤的含量可能会减少SGNA，以提供AF的速率和节奏控制。 Medtronic Inc.有很多 FDA批准的神经刺激剂用于疼痛和尿控制。本研究的目的是测试 可以有效地用于SCN的假说，即企业II神经刺激剂和3889 SNS铅可用于 和控制AF。如果结果有希望 并将这些发现转化为人类患者。我们提出以下特定目标：特定目的1： 在各种输出中执行SCN，以测试输出幅度重要的假设 确定神经调节的作用。具体而言，高输出刺激会导致SG损伤和 降低同情性语气，而非常低的输出SCN会导致SG和心脏神经发芽，因此 提高同情心。特定目的2：测试高输出scns的假设有效 在非常低的输出时，对AF的速率和节奏控制是心律不齐的。如果SG损坏是 SCN的抗心律失常作用的机制，然后遵循高输出SCN的必要 足以产生抗心律失常作用。另一方面，如果非常低的输出SCN会导致神经 发芽并增加交感神经，然后低输出刺激应具有心律失常。我们将使用一个 阵发性和持久性AF的犬类模型来检验这些假设。