Role of the Purkinje System in Long Duration Ventricular Fibrillation

浦肯野系统在长时心室颤动中的作用

• 批准号: 7662604
• 负责人: Derek J Dosdall
• 金额: $ 10.48万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-15 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7662604
• 关键词: Ablation; Actins; Action Potentials; Address; Adult; Affect; Area; Arrhythmia; Automobile Driving; Biology; Calcium; Calcium Signaling; Caliber; Canis familiaris; Cardiac; Cardiac Output; Cause of Death; Cell physiology; Cells; Cellular biology; Characteristics; Chemicals; Data; Diastole; Dose; Electric Countershock; Electrocardiogram; Electrodes; Endocardium; Ensure; Epicardium; Fiber; Foundations; Funding; Goals; Grant; Heart; Heart Arrest; Heart Atrium; Histocompatibility Testing; Individual; Institution; Instruction; Interruption; Intervention; Ischemia; Laboratory Research; Lead; Learning; Maintenance; Maps; Measures; Mechanics; Membrane Potentials; Mentors; Methods; Microelectrodes; Modeling; Morphologic artifacts; Morphology; Motion; Movement; Myocardial; Myocardial tissue; Myocardium; Myosin Type II; Needles; Organ; Patients; Pattern; Phase; Play; Positioning Attribute; Qualifying; Reporting; Research; Role; Shock; Signal Transduction; Sinoatrial Node; Site; Sodium Channel; Source; Structure of purkinje fibers; Subendocardial Layer; Survival Rate; System; Techniques; Testing; Time; Tissues; Training; Uncoupling Agents; Ventricular; Ventricular Fibrillation; Work; Writing; blebbistatin; clinically relevant; density; experience; heart cell; improved; inhibitor/antagonist; insight; ivabradine; member; optical fiber; prevent; research study; skills; small molecule; sudden cardiac death; systemin; voltage

DESCRIPTION (provided by applicant): Indirect evidence has indicated that the Purkinje system may be driving the rapid activation rate after the first few minutes of ventricular fibrillation (VF). This application proposes to measure the role of the Purkinje system in the maintenance of long duration VF (LDVF) and to determine if disruption of the Purkinje system may terminate or significantly alter LDVF activation patterns. Specific Aim 1 is to measure transmembrane voltage and action potential characteristics of the Purkinje system and working myocardium to determine if there are significant changes between these two tissue types during the global ischemia and rapid activation rate of LDVF. I will test the hypothesis that the rising membrane potential in the working myocardium raises the resting potential in the Purkinje system above threshold, which causes rapid activation within the Purkinje system. Specific Aim 2 is to directly map and measure the activity of the Purkinje system during LDVF. We will test the hypothesis that activation appears focally in the Purkinje system at sites close to Purkinje- myocardial junctions. Specific Aim 3 is to chemically ablate the Purkinje system to determine the influence of the Purkinje system on LDVF activation rates and patterns. Specific Aim 4 is to determine if there are pacing or pharmacological interventions which target the Purkinje system that may terminate VF or significantly lower the defibrillation threshold. During the mentored phase of the proposed work, I will learn valuable new cardiac activation mapping techniques, improve my presentation and writing skills, and learn cellular physiology through coursework. By the end of the mentored phase, I will be prepared and qualified to accept a tenure-track position at a leading research institution conducting cardiac arrhythmia research. During the independent phase, I will continue to investigate the Purkinje system in LDVF and establish an extramurally funded research laboratory to study the initiation and perpetuation of cardiac arrhythmias and to develop interventions to improve survival rates of patients with potentially lethal cardiac arrhythmias. RELEVANCE (See instructions): Approximately 450,000 sudden cardiac deaths (SCD) occur each year among U.S. adults. SCO often results from the onset of VF, which causes a dramatic decrease in cardiac output and irreversible damage to vital organs within a few minutes. The Purkinje system may play an important role in the maintenance of VF after the first 2 minutes and therapy targeting the Purkinje system may improve survival of these patients.

描述（由申请人提供）：间接证据表明，浦肯野系统可能会在心室纤颤（VF）的前几分钟后推动快速激活率。该应用程序提议衡量Purkinje系统在维持长持续时间VF（LDVF）中的作用，并确定Purkinje系统的破坏是否可能终止或显着改变LDVF激活模式。具体目的1是测量浦肯野系统的跨膜电压和动作电势特征，并在全球缺血期间这两种组织类型之间是否存在显着变化，而LDVF的快速激活速率之间是否存在显着变化。我将检验以下假设：工作心肌的膜电位上升会在阈值高于阈值的情况下增加静止电位，这会导致Purkinje系统内的快速激活。特定目标2是直接绘制和测量LDVF期间浦肯野系统的活性。我们将检验以下假设：激活在接近Purkinje-心肌连接处的位置的Purkinje系统中。具体目的3是在化学上消除Purkinje系统，以确定Purkinje系统对LDVF激活速率和模式的影响。特定目的4是确定针对可能终止VF或显着降低除颤阈值的Purkinje系统的起搏或药理干预措施。在拟议的工作的指导阶段，我将学习有价值的新心脏激活映射技术，提高我的演示和写作技巧，并通过课程学习细胞生理学。到指导阶段结束时，我将准备并有资格在领先的研究机构进行心律失常研究的领先研究机构中接受终身职位。在独立阶段，我将继续研究LDVF中的Purkinje系统，并建立一个由校外资助的研究实验室，以研究心律不齐的起始和永久性，并开发干预措施以提高潜在致命心律失常的患者的存活率。相关性（请参阅说明）：美国成年人每年发生大约450,000次心脏死亡（SCD）。 SCO通常是由VF发作引起的，VF的发作会在几分钟内引起心输出量的急剧下降和对重要器官的不可逆转损害。宾夕法尼亚系统可能在最初2分钟后在维持VF中起重要作用，针对珀肯吉系统的治疗可能会改善这些患者的存活率。