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美敦力 InterStim II 的假设 神经刺激器与 3889 SNS 导线结合可用于皮下神经刺激 (SCNS) 在犬模型中实现心房颤动（AF）的节律和速率控制。如果犬类研究成功的话 我们将进行试点临床试验，以促进房颤和快速心室反应患者的心率控制。 最终目标是激励美敦力公司进行额外的临床研究，以获得 FDA 批准 SCNS 作为管理 AF 的标签指示。该研究响应 RFA-RM-16-027，因为它将利用 针对新市场适应症的现有市场认可技术。 AF 是最常见的心律失常 在发达国家，这与死亡率和发病率的显着增加有关。药物用于 AF 的速率和节律控制并不总是成功，并且可能与显着的副作用相关。 房室结导管消融是药物难治性患者控制心率的一种选择 房颤和快速心室反应。然而，房室结消融使患者对起搏器产生依赖性。这是 非常需要开发一种无需使用药物或消融程序来控制 AF 的替代方法。 组织学研究表明，皮肤受到交感神经的良好支配。在狗中，节后 颈部和胸部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，胸部不同部位的皮下神经刺激（SCNS）会损害 SG 并降低 SG 神经活动 (SGNA)。这些发现提出了一个令人兴奋的可能性，即电刺激 皮肤的损伤可能会降低 SGNA，以提供 AF 的速率和节律控制。美敦力公司 (Medtronic Inc.) 拥有多项 FDA 批准用于疼痛和泌尿控制的神经刺激器。本研究的目的是测试 InterStim II 神经刺激器和 3889 SNS 导联可有效用于 SCNS 的假设 并控制自动对焦。如果结果有希望，就有可能激励美敦力赞助试点临床研究 并将这些发现转化为人类患者。我们提出以下具体目标： 具体目标 1： 在各种输出上执行 SCNS，以测试输出大小在以下方面很重要的假设： 确定神经调节的效果。具体来说，高输出刺激会导致 SG 损伤， 降低交感神经张力，同时非常低的输出 SCNS 会导致 SG 和心神经萌芽，因此 增加交感神经的张力。具体目标 2：检验高输出 SCNS 有效的假设 在 AF 的速率和节律控制中，当输出非常低时，会导致心律失常。如果 SG 损坏是 SCNS 的抗心律失常作用机制，那么高输出 SCNS 是必要的 并足以产生抗心律失常作用。另一方面，如果 SCNS 输出非常低会导致神经 发芽并增加交感神经张力，那么低输出刺激应该是致心律失常的。我们将使用一个 阵发性和持续性房颤的犬模型来检验这些假设。