ELECTROPHYSIOLOGICAL EFFECTS OF NEURAL REMODELING OF THE VENTRICLES

心室神经重塑的电生理效应

• 批准号: 8458497
• 负责人: KALYANAM SHIVKUMAR
• 金额: $ 39.48万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-15 至 2016-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8458497
• 关键词: Ablation; Adrenergic Agents; Adrenergic Fibers; Animal Model; Animals; Area; Arrhythmia; Attenuated; Autonomic nervous system; Bilateral; Biochemical; Biopsy; Cardiac; Cardiomyopathies; Cardiovascular system; Catheters; Cessation of life; Chest; Cicatrix; Clinical; Coronary; Disease; Efferent Neurons; Electrophysiology (science); Endocardium; Epicardium; Epidural Anesthesia; Excision; Fiber; Functional disorder; Ganglia; Goals; Health; Heart; Heart Transplantation; Histology; Human; Implantable Defibrillators; Infusion procedures; Knowledge; Left; Maps; Measurement; Morbidity - disease rate; Myocardial; Nerve; Nitroprusside; Norepinephrine; Operative Surgical Procedures; Output; Pathway interactions; Patients; Play; Prevention; Procedures; Property; Protocols documentation; Pulmonary artery structure; Recovery; Regulation; Research; Risk; Role; Structure of stellate ganglion; Sympathectomy; Sympathetic Ganglia; Testing; Therapeutic; Therapeutic Intervention; Thoracic spinal cord structure; United States; Ventricular; Ventricular Arrhythmia; Ventricular Fibrillation; Ventricular Remodeling; Ventricular Tachycardia; Ventricular septum; Work; adrenergic; base; clinical practice; cost; cost effective; density; improved; in vivo; mortality; nerve supply; novel; pericardial sac; prevent; public health relevance; regional difference; relating to nervous system; response; sudden cardiac death; therapy development

DESCRIPTION (provided by applicant): Sudden cardiac death (SCD) due to ventricular arrhythmias is the leading cause of mortality in the United States, resulting in 250,000 deaths/year. The autonomic nervous system plays a major role in the pathophysiology of arrhythmias leading to SCD and neuraxial modulation provides an important venue for therapeutic intervention. The major goal of our research is to investigate the role of cardiac sympathetic innervations in the genesis of arrhythmias, and that of neuraxial modulation in prevention of these arrhythmias in humans. The mechanisms underlying sympathetic control of myocardial excitability in normal and diseased human hearts, and specifically, regional differences (apex versus base, epicardium versus endocardium, right versus left stellate ganglion innervation) remain unknown and need to be studied. Further, myocardial scars seen in ischemic and non-ischemic cardiomyopathy show nerve sprouting at the border zone of scars due to neural remodeling, which has been implicated in the pathophysiology of ventricular arrhythmias. The functional effects of nerve stimulation in this setting and how neuraxial blockade works in humans in these diseases are still unknown and this knowledge can help guide therapy. In this proposal, electrophysiological effects of direct regional cardiac nerve stimulation and neuraxial modulation of the thoracic sympathetic ganglia will be investigated. Areas of the heart regulated by the right and left stellate ganglia will be delineated in patients undergoing interventional electrophysiology procedures and cardiac transplantation. Understanding neuraxial modulation has the potential to further develop therapies that target these pathways in the very near term. Therapies such as right, left, or bilateral cerviocothoracic sympathectomy which has been 're-introduced' into clinical practice (by our group and others) already show a lot of promise and could emerge as novel/elegant therapies that are also cost-effective for the prevention of SCD. Therefore, neuraxial modulation is an approach that has the potential to have a global impact given the prohibitive high cost and morbidity associated with implantable defibrillators which prevent their expanded use.

描述（由申请人提供）：室性心律失常导致的心源性猝死（SCD）是美国的主要死亡原因，每年导致250，000例死亡。自主神经系统在导致SCD的心律失常的病理生理学中起着重要作用，并且神经轴调节为治疗干预提供了重要场所。本研究的主要目的是探讨心脏交感神经支配在心律失常发生中的作用，以及神经轴调节在预防人类心律失常中的作用。在正常和患病的人类心脏中，交感神经控制心肌兴奋性的潜在机制，特别是区域差异（心尖与基底，心外膜与心内膜，右与左星状神经节神经支配）仍然未知，需要研究。此外，在缺血性和非缺血性心肌病中观察到的心肌瘢痕显示由于神经重塑而在瘢痕的边界区域处的神经发芽，这与室性心律失常的病理生理学有关。在这种情况下神经刺激的功能效应以及在这些疾病中神经轴阻滞如何在人类中起作用仍然是未知的，这些知识可以帮助指导治疗。在这个提议中，将研究直接区域心脏神经刺激和胸交感神经节的神经轴调制的电生理效应。将在接受介入电生理手术和心脏移植的患者中描绘由左右星状神经节调节的心脏区域。了解神经轴调节有可能在短期内进一步开发针对这些通路的治疗方法。治疗，如右，左，或双边颈胸交感神经切除术已被“重新引入”临床实践（由我们的小组和其他人）已经显示出很大的希望，并可能成为新的/优雅的治疗，也是成本效益的预防SCD。因此，考虑到与植入式假体相关的过高成本和发病率，防止其扩大使用，轴突调制是一种具有全球影响潜力的方法。