VIDEO IMAGING OF CARDIAC REENTRY INITIATION/TERMINATION

心脏折返启动/终止的视频成像

• 批准号: 6390475
• 负责人: RICHARD A. GRAY
• 金额: $ 21.53万
• 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/6390475
• 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.

心源性猝死是工业化国家死亡的主要原因。 室颤（VF）是大多数死亡的根本原因。 挽救这些人生命的唯一有效手段是从宽间距电极施加高能电场以终止VF。 如果在正常窦性或起搏节律的“脆弱期”施加这些高能量“电击”，也可诱发VF。 电击后的结果主要由电击期间跨膜电位（Vm）中的电荷决定。 然而，很少有人知道休克引起的整个心脏中Vm的变化，以及它们如何与休克后的事件有关。 据认为，在施加电场期间Vm的变化是以下各项的非线性函数：1）紧接在袜子之前的Vm模式; 2）电场的强度和时间过程（波形）;以及3）心脏细胞对刺激的动态响应。 我们假设：大于某个临界强度的电场阻止波前在整个心脏中传播，并且如果这些电击持续时间足够长，则将建立Vm的稳态模式。 在短持续时间的冲击结束时的Vm，对于一个恒定的电场在这个临界强度以上，可以预测从Vm的冲击开始时和稳定状态的Vm模式在长持续时间的冲击期间实现。II）心脏细胞的非线性反应，最重要的是全或无去极化和复极化，在可能导致折返的休克结束时新波前的产生中起重要作用。III）在激波结束时Vm的空间模式可以与再入形成相关，从而与激波导致的结果相关。 特别地，心脏相位的空间模式可以通过相位奇点与折返形式上相关，并且如果在电击结束时存在相位奇点，则折返将仅在电击之后发生。 我们的总体目标是提供第一个精确的理解的因素，确定在冲击过程中的Vm的变化，以及如何在所施加的电场结束时的Vm的模式影响的结果的冲击。 这一目标将通过以下方式实现：1）在起搏、单形性心动过速和纤颤期间给予电击期间和之后，记录心脏表面的Vm; 2）记录它们对分离心室肌细胞中刺激的反应; 3）将电击结束时的膜电位模式与结果相关联。 此外，Vm在单细胞和模式的Vm从心脏表面的变化将分析的心脏相位变量，它提供了一个数学框架的检查细胞动力学和折返波。