Electrophysiological Effects of Neural Remodeling of the Ventricles

心室神经重塑的电生理效应

• 批准号: 7078849
• 负责人: KALYANAM SHIVKUMAR
• 金额: $ 38.63万
• 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 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7078849
• 关键词: cardiovascular disorder therapy; clinical research; computed axial tomography; electrophysiology; ganglionic blocking agents; heart disorder chemotherapy; heart innervation; heart ventricle; human subject; human therapy evaluation; magnetic resonance imaging; myocardial ischemia /hypoxia; myocardium disorder; neuropharmacology; patient oriented research; reflex; sudden cardiac death; sympathetic nervous system; tachycardia

DESCRIPTION (provided by applicant): Sudden cardiac death (SCD) is the leading cause of death in the United States and accounts for almost 250,000 deaths/year. The vast majority of these deaths are thought to be due to ventricular tachyarrhythmias. Several cellular and molecular events that underlie sudden arrhythmic death have been well characterized. However, a major challenge in the field of cardiac electrophysiology is to understand how events at a cellular and molecular level translate into behavior of arrhythmias in the whole organ. The autonomic nervous system is a powerful regulator of arrhythmogenesis. Heightened sympathetic activity has well-known proarrhythmic consequences, including increased ventricular ectopy, decreased VF threshold, and increased inherent dynamic instability of cardiac wave propagation. However, the electrophysiological mechanisms that underlie such regulation are not well understood. The Neural Remodeling Hypothesis for SCD, states that in addition to electrical and structural remodeling of the ventricles, there is functional and structural remodeling of the cardiac neurons which directly leads to an increased susceptibility to SCD. This hypothesis will be tested in patients with ventricular dysfunction in this proposal. Specifically, we will determine whether electrophysiological heterogeneity (between normal and diseased myocardium) is enhanced to a greater extent by reflex-mediated sympathetic stimulation compared to direct simulation of sympathetic receptors in humans. We propose to study patients undergoing interventional electrophysiology procedures. In the long term, understanding the fundamental aspects of SCD is likely to result in the development of novel therapies for its prevention.

描述（由申请人提供）：心源性猝死 (SCD) 是美国的首要死因，每年导致近 250,000 人死亡。这些死亡中的绝大多数被认为是由于室性快速心律失常所致。心律失常性猝死背后的几种细胞和分子事件已经得到了很好的表征。然而，心脏电生理学领域的一个主要挑战是了解细胞和分子水平的事件如何转化为整个器官的心律失常行为。自主神经系统是心律失常发生的强大调节器。交感神经活动增强具有众所周知的致心律失常后果，包括心室异位增加、室颤阈值降低以及心电波传播的固有动态不稳定性增加。然而，这种调节背后的电生理机制尚不清楚。 SCD 的神经重塑假说指出，除了心室的电和结构重塑之外，心脏神经元也存在功能和结构重塑，这直接导致 SCD 的易感性增加。在本提案中，该假设将在心室功能障碍患者中进行测试。具体来说，我们将确定与直接模拟人类交感神经受体相比，反射介导的交感神经刺激是否会更大程度地增强电生理异质性（正常心肌和患病心肌之间）。我们建议研究接受介入电生理学手术的患者。从长远来看，了解 SCD 的基本方面可能会导致开发新的预防疗法。