VIDEO IMAGING OF CARDIAC REENTRY INITIATION/TERMINATION

心脏折返启动/终止的视频成像

• 批准号: 6130867
• 负责人: RICHARD A. GRAY
• 金额: $ 25.99万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6130867
• 关键词: bioimaging /biomedical imaging; cardiac myocytes; charge coupled device camera; electric countershock heart resuscitation; heart ventricle; implantable defibrillators; laboratory rabbit; mathematical model; membrane potentials; model design /development; tachycardia; ventricular fibrillation; videotape /videodisc

Sudden cardiac death is the leading cause of fatalities in the industrialized world. Ventricular fibrillation (VF) is the underlying cause of the majority of these deaths. The only effective means to save the lives of these individuals is to apply high energy electric fields from widely spaced electrodes to terminate VF. These high energy "shocks" can also induce VF, if they are applied during the "vulnerable period" of normal sinus or pace rhythms. The outcome following a shock is determined largely by the charges in transmembrane potential (Vm) during the shock. However, very little is known about the shock- induced changes in Vm in the whole heart and how they relate to the events following a shock. It is thought that the changes in Vm during applied electric fields is a nonlinear function of: 1) the Vm pattern immediately before the sock; 2) the strength and time course (waveform) of the electric field; and 3) the dynamic response of cardiac cells to stimuli. We hypothesize that: I Electric fields greater than some critical strength prevent wave front propagation throughout the heart, and if these shocks are sufficiently long in duration, a steady state pattern of Vm will be established. Vm at the end of short duration shocks, for a constant electric field above this critical strength, can be predicted from Vm at the beginning of the shock and the steady state Vm pattern achieved during long duration shocks. II) The nonlinear response of cardiac cells, most importantly all-or-none depolarization and repolarization, plays an important role in the generation of new wave fronts at the end of the shock which may lead to reentry. III) The spatial pattern of Vm at the end of the shock can be related to reentry formation and hence the outcome resulting from the shock. In particular, spatial patterns of cardiac phase can be formally related to reentry via phase singularities and reentry will only occur following a shock if a phase singularity exists at the end of the shock. Our overall goal is to provide the first precise understanding of the factors that determine the changes in Vm during a shock and how the pattern of Vm at the end of the applied electric field affects the outcome of the shock. This goal will be achieved by: 1) recording Vm from the surface of the heart during and following electric shocks given during pacing, monomorphic tachycardia, and fibrillation; 2) recording them response to stimuli in isolated ventricular myocytes; and 3) relating the patterns of membrane potential at the end of shocks to outcome. Furthermore, changes in Vm in single cells and patterns of Vm from the heart surface will be analyzed in terms of a cardiac phase variable which provides a mathematical framework for the examination of cellular dynamics and reentrant waves.

在工业化世界，心脏性猝死是导致死亡的主要原因。室颤(VF)是这些死亡中的大多数的潜在原因。挽救这些人生命的唯一有效方法是从分布广泛的电极施加高能电场来终止VF。如果在正常窦性心律或起搏节律的“易损期”应用，这些高能“电击”也能诱发室颤。休克后的结局在很大程度上取决于休克期间跨膜电位(Vm)的电荷。然而，关于电击引起的整个心脏Vm的变化以及它们与电击后事件的关系，人们知之甚少。认为外加电场时Vm的变化是一个非线性函数：1)紧接袜子前的Vm模式；2)电场的强度和时程(波形)；3)心肌细胞对刺激的动态反应。我们假设：I大于某一临界强度的电场可阻止波前在心脏中传播，如果这些电击持续时间足够长，则将建立Vm的稳态模式。对于高于该临界强度的恒定电场，短持续冲击结束时的Vm可以根据冲击开始时的Vm和在长持续冲击期间获得的稳定状态Vm模式来预测。Ii)心肌细胞的非线性反应，最重要的是全有或全无去极化和复极化，在休克结束时可能导致再入的新波前的产生中起着重要作用。3)激波结束时Vm的空间分布可能与再入形成有关，从而与激波的结果有关。特别是，心脏相位的空间模式可以通过相位奇异性形式上与再入相关联，并且只有在休克结束时存在相位奇异性时，再入才会发生。我们的总体目标是首次准确地了解决定电击期间Vm变化的因素，以及在外加电场结束时Vm的模式如何影响电击的结果。这一目标将通过：1)在起搏、单形性心动过速和纤颤过程中和之后记录心脏表面的Vm；2)记录它们对刺激的反应；3)将电击结束时的膜电位模式与预后联系起来。此外，单个细胞的Vm的变化和来自心脏表面的Vm的模式将根据心脏相位变量进行分析，该变量为检查细胞动力学和折返波提供了一个数学框架。