Mechanistic refinement of non-invasive autonomic neuromodulation for cardiac arrhythmia

自主神经系统在心律失常的发病机制中具有重要作用， 为治疗干预提供了关键机会。自主神经系统的调节 已经尝试了许多方法，包括外科交感神经切除术、基于导管的 消融手术和经皮方法。虽然自主神经支配已经被证明 具有显着的影响，对促炎性，相互作用的复杂网络和最佳的 中断该网络的策略没有得到充分的描述。为了进一步研究该领域，本研究 将整合神经科学的既定原则和技术，研究自主神经的作用。 神经调节治疗心律失常。调查将集中在以下方面的能力： 重复经皮磁刺激（TcMS）调节自主神经突触强度 心脏神经支配这种非破坏性和非侵入性技术的可行性得到了以下方面的支持： 博士Markman最近发表在JAMA上的研究成果，用抑制性的神经递质靶向颈部交感神经链， 室性心动过速（VT）风暴患者的TcMS方案。拟议的研究计划旨在 提高对自主神经调节的心脏效应的理解，并评估其疗效 VT风暴患者的TcMS。目的1旨在描述心脏电生理效应 自主神经调节的侵入性测量传导特性以及水平 在神经调节之前和之后的儿茶酚胺和炎性细胞因子。这将发展到至关重要的 用于表征神经-心脏相互作用的工具，允许明确评估其复杂性 关系 目的2旨在描述自主神经调节的心脏电生理效应， 侵入性地测量传导特性以及儿茶酚胺和炎症的水平， 神经调节前后的细胞因子。结合起来，这些目标的发现将产生关键的 关于复杂的心脏神经通路的机械特性的信息，并帮助 确立一种新型神经调节方法的作用。此外，这项研究将促进批判性 神经科学家和心血管医学之间重要的持续跨学科合作。 博士马克曼是一名早期职业调查员，也是心脏电生理学研究员，他有一个长期目标 建立自主神经调节的独立研究项目， 机械地定义了心律失常中涉及的复杂神经回路。这些研究目的 是全面培训计划的一部分，并将由一个指导和咨询团队进行监督 由心律失常和神经科学研究的国家领导人组成，并将指导他过渡到一个 独立资助的研究生涯。

The autonomic nervous system has an important role in the pathogenesis of cardiac arrhythmias thus providing a critical opportunity for therapeutic intervention. Modulation of the autonomic nervous system has been attempted through numerous means including surgical sympathectomy, catheter-based ablation procedures, and transcutaneous approaches. Although autonomic innervation has been shown to have a significant effect on arrhythmogenicity, the complex network of interactions and the optimal strategies for interrupting this network are inadequately characterized. To further the field, this research will integrate established principles and techniques from neuroscience to study the role of autonomic neuromodulation in the treatment of cardiac arrhythmias. The investigation will focus on the ability of repetitive transcutaneous magnetic stimulation (TcMS) to modulate synaptic strength of autonomic cardiac innervation. The feasibility of this non-destructive and non-invasive technology is supported by Dr. Markman’s recent work published in JAMA targeting the cervical sympathetic chain with an inhibitory TcMS protocol in patients with ventricular tachycardia (VT) storm. The proposed research plan aims to improve understanding of the cardiac effects of autonomic neuromodulation, and to assess the efficacy of TcMS in patients with VT storm. Aim 1 seeks to characterize the cardiac electrophysiological effects of autonomic neuromodulation by invasively measuring conduction properties as well as levels of catecholamines and inflammatory cytokines before and after neuromodulation. This will develop critical tools for characterizing neural-cardiac interactions, allowing definitive assessment of their complex relationship. Aim 2 seeks to characterize the cardiac electrophysiological effects of autonomic neuromodulation by invasively measuring conduction properties as well as levels of catecholamines and inflammatory cytokines before and after neuromodulation. In combination, the findings from these aims will yield critical information regarding the mechanistic characterization of complex cardiac-neural pathways and help establish the role of a novel method of neuromodulation. In addition, this research will promote critically important continued interdisciplinary collaboration between neuroscientists and cardiovascular medicine. Dr. Markman, an early career investigator and a fellow in cardiac electrophysiology, has a long-term goal of establishing an independent research program in autonomic neuromodulation focused on mechanistically defining the complex neural circuits involved in cardiac arrhythmias. These research aims are part of a comprehensive training plan and will be supervised by a mentorship and advisory team consisting of national leaders in arrhythmia and neuroscience research and will guide his transition to an independently funded research career.