Mechanistic refinement of non-invasive autonomic neuromodulation for cardiac arrhythmia

非侵入性自主神经调节治疗心律失常的机制完善

• 批准号: 10525948
• 负责人: Timothy Markman
• 金额: $ 17.33万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10525948
• 关键词: Ablation; Advisory Committees; American; Arrhythmia; Autonomic Pathways; Autonomic ganglion; Autonomic nervous system; Cardiac; Cardiac Electrophysiologic Techniques; Cardiac ablation; Cardiovascular Diseases; Cardiovascular system; Catecholamines; Catheters; Cervical; Clinical; Clinical Trials; Complement; Complex; Critical Illness; Data; Development; Electrophysiology (science); Evaluation; Frequencies; Funding; Future; Goals; Health Resources; Hour; Inflammatory; Interruption; Investigation; Magnetism; Master of Science; Measurable; Measurement; Measures; Medicine; Mentors; Mentorship; Methodology; Methods; Morbidity - disease rate; Neural Pathways; Neurosciences; Neurosciences Research; Operative Surgical Procedures; Pathogenesis; Pathway interactions; Patients; Peripheral; Physiological; Positioning Attribute; Procedures; Property; Protocols documentation; Publishing; Randomized; Refractory; Reproducibility; Research; Research Personnel; Risk; Role; Structure of stellate ganglion; Supervision; Sympathectomy; Synapses; Techniques; Technology; Testing; Therapeutic; Therapeutic Intervention; Training; Training Programs; Translational Research; United States National Institutes of Health; Vasodilation; Ventricular; Ventricular Arrhythmia; Ventricular Tachycardia; Work; arm; base; career; career development; cohort; cytokine; efficacy evaluation; experience; heart innervation; improved; innovation; interdisciplinary collaboration; ischemic cardiomyopathy; mortality; nerve supply; neural circuit; neuromechanism; neuroregulation; novel; patient oriented research; primary endpoint; programs; relating to nervous system; sudden cardiac death; tool; transcutaneous stimulation

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.

自主神经系统在心律失常的发病机制中具有重要作用，因此 为自主神经系统的治疗干预提供了重要的机会。 已尝试通过多种方式进行治疗，包括手术交感神经切除术、基于导管的 尽管已经显示了自主神经支配。 对心律失常性、复杂的相互作用网络和最佳效果有显着影响 为了进一步推进该领域，本研究对中断该网络的策略进行了充分的描述。 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 该研究将集中于神经调节治疗心律失常的能力。 经皮重复磁刺激（TcMS）调节自主神经突触强度 这种非破坏性和非侵入性技术的可行性得到了支持。 马克曼博士最近在《美国医学会杂志》上发表的研究成果，以抑制颈交感神经链为目标 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对心脏影响的了解，并评估其功效 TcMS 在 VT 风暴患者中的应用目标 1 旨在描述心脏电生理效应的特征。 通过侵入性测量传导特性以及水平来进行自主神经调节 儿茶酚胺和炎症细胞因子在神经调节前后的变化至关重要。 用于表征神经心脏相互作用的工具，可以对其复杂性进行明确评估 关系。 目标 2 试图通过以下方式表征自主神经调节的心脏电生理效应： 有创地测量传导特性以及儿茶酚胺和炎症的水平 结合起来，这些目标的发现将产生至关重要的结果。 有关复杂心脏神经通路的机械特征的信息和帮助 此外，这项研究将极大地促进神经调节新方法的作用。 神经科学家和心血管医学之间持续重要的跨学科合作。 马克曼博士是一名早期职业研究员和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计划，重点关注 这些研究的目的是从机制上定义与心律失常有关的复杂神经回路。 是综合培训计划的一部分，并将由指导和咨询团队监督 由心律失常和神经科学研究领域的国家领导人组成，将指导他过渡到 独立资助的研究生涯。