VIDEO IMAGING OF CARDIAC REENTRY INITIATION/TERMINATION

在工业化国家，心脏性猝死是导致死亡的主要原因。心室颤动（VF）是大多数此类死亡的根本原因。挽救这些人生命的唯一有效手段是利用大间距电极产生的高能电场来终止VF。如果在正常窦性或心律的“脆弱期”施加这些高能“冲击”，也会诱发室性心动过速。休克后的结果在很大程度上是由休克期间跨膜电位（Vm）中的电荷决定的。然而，对于休克引起的整个心脏Vm的变化以及它们与休克后事件的关系知之甚少。认为在外加电场作用下，Vm的变化是以下因素的非线性函数：1)紧接在袜子之前的Vm模式；2)电场强度和时程（波形）；3)心肌细胞对刺激的动态反应。我们假设：大于某个临界强度的电场阻止波前在整个心脏的传播，如果这些冲击持续时间足够长，将建立一个稳定的Vm模式。短时间电击结束时的Vm，对于高于此临界强度的恒定电场，可以从电击开始时的Vm和长时间电击期间实现的稳态Vm模式来预测。II)心肌细胞的非线性响应，最重要的是全或无去极化和复极化，在激波结束时可能导致再入的新波阵面产生中起重要作用。III)激波结束时Vm的空间格局可能与再入形成以及由此产生的激波结果有关。特别是，心脏相的空间模式可以通过相奇点与再入有正式的联系，并且只有在激波结束时存在相奇点时才会发生再入。我们的总体目标是提供第一个精确的理解，决定在电击期间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。这一目标将通过以下方式实现：1)在起搏、单型心动过速和纤颤期间和之后，从心脏表面记录Vm；2)在分离的心室肌细胞中记录它们对刺激的反应；3)将休克结束时的膜电位模式与结果联系起来。此外，将根据心脏相变量分析单个细胞中Vm的变化和心脏表面Vm的模式，这为检查细胞动力学和重入波提供了数学框架。

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.