Skin Sympathetic Nerve Activity and Cardiac Arrhythmias

皮肤交感神经活动和心律失常

• 批准号: 9139044
• 负责人: Thomas H Everett
• 金额: $ 77.54万
• 依托单位: ARRHYTHMOTECH, LLC
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9139044
• 关键词: Applications Grants; Arousal; Arrhythmia; Atrial Fibrillation; Canis familiaris; Cardiac; Cardiology; Clinic; Clinical Research; Cocaine; Detection; Devices; Dexmedetomidine; Disease; Electrocardiogram; Electrodes; Funding; Future; Ganglionic Blockers; Grant; Heart Atrium; Heart failure; Human; Indiana; Injection of therapeutic agent; Institutes; Laboratories; Laboratory Research; Lead; Legal patent; Lidocaine; Marketing; Measurement; Measures; Medical center; Methods; Microelectrodes; Modeling; Muscle; Myocardial; Nerve; Operative Surgical Procedures; Pathogenesis; Patients; Pattern; Phase; Physiologic pulse; Procedures; Radiofrequency Catheter Ablation; Research; Risk; Sinus; Skin; Small Business Technology Transfer Research; Stimulus; Stratification; Structure of stellate ganglion; Structure of ulnar nerve; Subcutaneous Tissue; Surface; Techniques; Testing; Thoracotomy; Universities; Ventricular Arrhythmia; arm; autonomic nerve; clinical investigation; clinically significant; commercial application; commercialization; heart rate variability; human subject; instrument; median nerve; neuroregulation; novel marker; phase 2 study; prototype; public health relevance; research and development; response; subcutaneous; success; tool

 DESCRIPTION (provided by applicant): The objective of this Phase II STTR grant application is to continue the R/R&D efforts initiated in Phase I. The long-term objective for Arrhythmotech is to develop and market an instrument for the simultaneous recording of sympathetic nerve activity (SNA) and electrocardiogram (ECG) using electrodes on the skin. This method (neuECG) was discovered in Dr. Chen's research laboratory at the Krannert Institute of Cardiology, and a patent application has been filed by Indiana University. Arrhythmotech LLC was founded to further advance this concept, and we propose that neuECG will have significant commercial value by providing a new tool for arrhythmia prediction and detection. Significant progress has been made with the Phase I STTR funding. Phase II will expand the clinical research to firmly validate the neuECG as a method to estimate cardiac sympathetic tone, and to develop and test prototypes that can be used for future clinical investigations, while laying th groundwork for Phase III commercialization of the first application. Sympathetic tone is important in cardiac arrhythmogenesis. However, the existing method of SNA measurement is either invasive or not accurate. We have therefore developed methods to directly record SNA from either subcutaneous tissues or on the surface of the skin in canine models. We found that both subcutaneous nerve activity (SCNA) and superficial skin sympathetic nerve activity (SKNA) closely correlate with stellate ganglia nerve activity (SGNA) in ambulatory dogs. With the generous support of a Phase I STTR grant, we were able to obtain preliminary results in human patients that strongly suggest the validity of SKNA in estimating sympathetic tone. We have successfully developed prototypes that can be used for long-term SKNA recording. We will pursue the following Specific Aims. Specific Aim 1: Unequivocally validate SKNA as a highly accurate non-invasive measure of skin SNA with simultaneous microelectrode recordings. These studies will be performed by Dr. Ronald Victor of Cedars-Sinai Medical Center. Specific Aim 2: To test the hypothesis that lidocaine injection into the stellate ganglion or surgical stellectomy will reduce or eliminate the SKNA recorded from the arms. These studies will be done by Dr. Yong-Mei Cha of the Mayo Clinic. In addition to validating SKNA as a measure of skin SNA, these studies may also lead to commercial applications by providing a tool to measure the success of neuromodulation procedures. Specific Aim 3: Demonstrate that SKNA as measured by neuECG can serve as a novel biomarker for testing atrial fibrillation vulnerability. These studies will be done at Indiana University. Our preliminary results indicate that specific SKNA patterns are closely associated with the spontaneous occurrence of paroxysmal AF. Those specific patterns can be considered as novel biomarkers that are useful in arrhythmia management, such as guiding radiofrequency catheter ablation procedures and predict the long term success of these procedures. Successful completion of these 3 specific aims will give Arrhythmotech, LLC an excellent platform for future commercial applications.

 描述（由申请人提供）：此第二阶段STTR资助申请的目的是继续在第一阶段开始的R/R&D工作。Arrhythmotech的长期目标是开发和销售一种使用皮肤上的电极同时记录交感神经活动（SNA）和心电图（ECG）的仪器。这种方法（neuECG）是在Krannert心脏病研究所的陈博士的研究实验室发现的，并已由印第安纳州大学提交了专利申请。Arrhythmotech LLC的成立是为了进一步推进这一概念，我们认为neuECG将通过提供心律失常预测和检测的新工具而具有重大的商业价值。在第一阶段短期信托基金供资方面取得了重大进展。第二阶段将扩大临床研究，以坚定地验证neuECG作为估计心脏交感神经张力的方法，并开发和测试可用于未来临床研究的原型，同时为第一个应用的第三阶段商业化奠定基础。交感神经紧张在心肌梗死中起重要作用。然而，现有的SNA测量方法要么是侵入性的，要么是不准确的。因此，我们已经开发出直接记录SNA的方法，无论是从皮下组织或在犬模型的皮肤表面。我们发现，皮下神经活动（SCNA）和浅表皮肤交感神经活动（SKNA）密切相关的星状神经节神经活动（SGNA）在步行狗。在第一阶段STTR资助的慷慨支持下，我们能够在人类患者中获得初步结果，这些结果强烈表明SKNA在估计交感神经张力方面的有效性。我们已经成功开发出可用于长期SKNA记录的原型。我们将追求以下具体目标。具体目标1：明确验证SKNA是一种高度准确的非侵入性皮肤SNA测量方法，同时进行微电极记录。这些研究将由Cedars-Sinai Medical Center的罗纳德维克托博士进行。具体目标二：检验利多卡因注射到星状神经节或手术切除术将减少或消除手臂记录的SKNA的假设。这些研究将由马约诊所的查永梅博士完成。除了验证SKNA作为皮肤SNA的测量之外，这些研究还可以通过提供测量神经调节程序的成功的工具而导致商业应用。具体目标3：证明通过neuECG测量的SKNA可作为检测房颤易损性的新型生物标志物。这些研究将在印第安纳州大学进行。我们的初步结果表明，特定的SKNA模式与阵发性AF的自发发生密切相关。这些特定的模式可以被认为是一种新的生物标志物，可用于心律失常的管理，如指导射频导管消融术，并预测这些手术的长期成功。成功完成这3个具体目标将为Arrhythmotech，LLC提供一个未来商业应用的绝佳平台。