Sympathetic Nerve Activity Recorded From the Skin and Cardiac Arrhythmias

描述(由申请人提供)：该研究项目的广泛和长期目标是使用、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。Arterormotech LLC是为了进一步推进这一概念而发展起来的，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非侵入性工具而具有重要的商业价值。交感神经张力在心律失常的发生中起重要作用。心率变异性分析和显微神经学记录是评估交感神经张力的标准技术。然而，这些技术有多个限制。神经心电图仪是为了同时记录人体皮肤上的心电和神经活动而研制的。与陈博士的实验室合作，我们在人类患者身上取得了强有力的初步结果，证明了在正常志愿者和术后心房颤动和电风暴患者中成功记录了中性心电。在这些初步研究中，中性心电记录显示出与SNA一致的电信号，SNA与心率加速、房颤和室性心律失常相关。我们认为，中性心电可作为预测心律失常和心脏性猝死的一种新的诊断工具。此外，它可能有助于周围神经疾病的诊断。 系统，如神经肌肉疾病。在这一阶段的应用中，我们设计了两项临床研究，以证明中性心电记录在正常志愿者和心律失常患者中的可行性和实用性。一旦完成，我们将立即申请第二阶段资金，将中性心电商业化，供人类使用。具体目的1：记录正常志愿者的同步心电和体感诱发电位，并将神经活动与心率进行相关分析。我们将同意正常志愿者进行这项研究。我们将使用标准的肢体导联和胸导联将心电电极放置在皮肤上。这些信号被数字化和滤波，以同时记录心电和SNA。基线记录后，患者将接受2分钟的冷水浸泡试验，然后进行Valsalva动作。这些数据将被分析以检验这样的假设，即从皮肤同时记录SNA是可行的，并且SNA记录与正常志愿者的心率加速相关。具体目的2：记录心律失常患者的同步心电图和SNA，并将神经活动增加与心律失常的发生联系起来。对于复发性心律失常的患者，我们将在床边进行持续的中性心电记录。这些数据将被分析，以确定SNA是否存在于疾病患者的皮肤上，以及SNA是否与心律失常的发生相关。这一结果将被用来检验这样的假设，即在心脏病患者中进行连续的中性心电记录是可行的，并且SNA可以预测即将发生的心律失常。

DESCRIPTION (provided by applicant): The broad and long-term objective of this research project is to use, 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 developed to further advance this concept and we propose that neuECG has a significant commercial value by providing a new non-invasive tool for arrhythmia prediction and detection. Sympathetic tone is important in cardiac arrhythmogenesis. Heart rate variability analyses and microneurography recordings are standard techniques to assess sympathetic tone. However, these techniques have multiple limitations. The neuECG was developed to record ECG and nerve activity simultaneously on the skin of human subjects. In collaboration with Dr. Chen's lab, we have obtained strong preliminary results in human patients to document the successful recording of neuECG in normal volunteers and in patients with postoperative atrial fibrillation and electrical storm. In these preliminary studies, neuECG recording showed electrical signals consistent with SNA, and that the SNA correlated with heart rate acceleration, atrial fibrillation and ventricular arrhythmias. We propose that the neuECG may serve as a new diagnostic tool for the prediction of cardiac arrhythmias and sudden cardiac death. In addition, it may be helpful in the diagnosis of diseases involving the peripheral nervous system, such as neuromuscular diseases. In this Phase 1 application, we have designed two clinical studies to document the feasibility and utility of neuECG recording in normal volunteers and in patients with cardiac arrhythmias. Once this is complete, we will immediately apply for Phase 2 funding to commercialize the neuECG for human use. Specific Aim 1: To record simultaneous ECG and SNA in normal volunteers and correlate the nerve activity to heart rate. We will consent normal volunteers for this study. We will place ECG electrodes on the skin using standard limb lead and chest lead configurations. The signals are digitized and filtered to record ECG and SNA simultaneously. After baseline recordings, the patients will undergo 2-min cold water immersion test, followed by Valsalva maneuver. The data will be analyzed to test the hypothesis that it is feasible to simultaneously record SNA from the skin, and that SNA recordings correlate with heart rate acceleration in normal volunteers. Specific Aim 2: To record simultaneous ECG and SNA in patients with cardiac arrhythmias and correlate an increase in nerve activity to arrhythmia onset. We will perform continuous neuECG recording at the bedside in patients with recurrent cardiac arrhythmias. The data will be analyzed to determine if the SNA are present on the skin of the diseased patients, and if the SNA correlates with the onset of cardiac arrhythmias. The results will be used to test the hypothesis that a continuous neuECG recording is feasible in patients with heart diseases, and that SNA predicts the impending onset of cardiac arrhythmias.