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起着重要作用。 为治疗干预提供了一个关键的机会。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 消融手术和经皮途径。尽管自主神经支配已被证明 对心律失常的诱发性有显著影响，复杂的相互作用网络和最佳 中断这一网络的策略没有得到充分的描述。为了推动这一领域的发展，这项研究 将整合神经科学的既定原理和技术来研究自主神经的作用 神经调节在心律失常治疗中的作用调查的重点将是 重复经皮磁刺激对自主神经突触强度的调节作用 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 马克曼博士最近在《美国医学会杂志》上发表的一项研究，针对颈部交感神经链的抑制作用 TCMS方案在室性心动过速(VT)患者中的应用拟议的研究计划旨在 提高对自主神经调节对心脏影响的理解，并评估其疗效 室性心动过速患者的中医辨证分型。目的1研究心脏电生理效应 通过侵入性测量传导特性以及水平的自主神经调节 神经调节前后的儿茶酚胺和炎性细胞因子。这将发展成关键的 用于表征神经-心脏相互作用的工具，允许对其复杂性进行最终评估 两性关系。 目的2研究自主神经调节的心脏电生理效应。 侵入性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。综合起来，来自这些目标的发现将产生关键的 关于复杂心脏-神经通路的机制特征的信息和帮助 确定一种新的神经调节方法的作用。此外，这项研究还将对 神经学家和心血管医学之间重要的持续跨学科合作。 马克曼博士是一名职业生涯早期的研究员，也是心脏电生理学的研究员，他有一个长期的目标 在自主神经调节方面建立一个独立的研究计划，重点是 从机械上定义与心律失常有关的复杂神经回路。这些研究的目的是 是全面培训计划的一部分，并将由指导和咨询团队监督 由心律失常和神经科学研究的国家领导者组成，并将指导他向 独立资助的研究事业。

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.