Skin Sympathetic Nerve Activity and Cardiac Arrhythmias

 描述(由申请者提供)：这项第二阶段STTR拨款申请的目标是继续第一阶段开始的研发工作。ARTERTMOTECH的长期目标是开发和销售一种使用皮肤电极同时记录交感神经活动(SNA)和心电图(CG)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中发现的，印第安纳大学已经提交了专利申请。ARRETRATMOTECH LLC的成立是为了进一步推进这一概念，我们认为中性心电通过为心律失常的预测和检测提供一种新的工具，将具有重要的商业价值。STTR第一阶段资金已取得重大进展。第二阶段将扩大临床研究，以坚定地确认中性心电作为一种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，同时为第三阶段第一个应用的商业化奠定基础。交感神经张力在心律失常的发生中起重要作用。然而，现有的SNA测量方法要么具有侵入性，要么不准确。因此，我们开发了在犬模型中直接从皮下组织或皮肤表面记录SNA的方法。我们发现，活动犬的皮下神经活动(SCNA)和皮肤浅交感神经活动(SKNA)都与星状神经节活动(SGNA)密切相关。在第一阶段STTR赠款的慷慨支持下，我们能够在人类患者中获得初步结果，有力地表明SKNA在估计交感神经音调方面的有效性。我们已经成功地开发出可用于长期SKNA记录的原型。我们将追求以下具体目标。具体目标1：通过同步微电极记录，明确验证SKNA作为皮肤SNA的高精度非侵入性测量。这些研究将由锡达斯-西奈医学中心的罗纳德·维克托博士进行。具体目的2：验证假设，即利多卡因注射到星状神经节或手术切除星状神经节将减少或消除从手臂记录的SKNA。这些研究将由梅奥诊所的查永美博士完成。除了验证SKNA作为皮肤SNA的衡量标准外，这些研究还可能通过提供一种工具来衡量神经调节程序的成功程度，从而导致商业应用。具体目的3：证明中性心电测定的SKNA可作为检测房颤易感性的一种新的生物标志物。这些研究将在印第安纳大学进行。我们的初步结果表明，特定的SKNA模式与阵发性房颤的自发发生密切相关。这些特定的模式可以被认为是在心律失常治疗中有用的新的生物标志物，例如指导射频导管消融手术并预测这些手术的长期成功。这三个具体目标的成功实现将为Arartermotech，LLC未来的商业应用提供一个极好的平台。

 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.