TRANSMEMBRANE POTENTIAL MAPPING OF DEFIBRILLATION

除颤的跨膜电位图

• 批准号: 2854238
• 负责人: STEPHEN B KNISLEY
• 金额: $ 14.43万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-07-01 至 2003-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2854238
• 关键词: electric countershock heart resuscitation; electric field; fluorescent dye /probe; heart electrical activity; laboratory rabbit; lasers; membrane potentials; microelectrodes; myocardial ischemia /hypoxia; myocardium; sodium channel

An electric defibrillation shock is the only effective therapy to halt ventricular fibrillation. Improvements in the therapy will require knowledge of how electric shocks interact with the myocardium to change cardiac transmembrane voltages. An "activating function" is hypothesized to govern this interaction. This grant will test the hypothesis by 1) developing a method to optically mark hearts that will indicate the locations from which transmembrane voltages were recorded, 2) determining the relationships of the first and second spatial derivatives of the cardiac extracellular voltages induced by electric shocks to the changes in transmembrane voltages, 3) determining the relationships of myocardial structural inhomogeneities to the changes in transmembrane voltages produced by electric shocks, and 4) determining whether cell-to-cell uncoupling by ischemia, often present during defibrillation, alters the changes in transmembrane voltages produced by electric shocks. Transmembrane voltage changes in rabbit hearts will be measured with laser-scanner mapping of transmembrane voltage-sensitive dye fluorescence. To determine relationships between myocardial structure and transmembrane voltage changes, we will optically mark recording locations with the laser beam. Spatial derivatives of shock extracellular voltages will be produced in one and two dimensions with transparent indium tin oxide (ITO) and metallic shocking electrodes. The derivatives will be measured with metallic and ITO recording electrodes. Mapping of intracellular 6-carboxyfluorescein fluorescence recovery after photobleaching (FRAP) will indicate roles of intracellular diffusion that corresponds to the myocardial multicellular structure in the relationships that govern transmembrane voltage changes. FRAP will also indicate changes in diffusion constants introduced by cell-to-cell uncoupling during ischemia. Whether the uncoupling impacts on transmembrane voltage changes produced by shocks will be determined for global ischemia and for borders of ischemic regions. Thus, major factors responsible for transmembrane voltage changes during defibrillation in normal and ischemic hearts will be determined. This knowledge will help to optimize electrical therapy for life-threatening arrhythmias.

电除颤电击是阻止心室颤动的唯一有效疗法。 治疗的改进需要了解电击如何与心肌相互作用以改变心脏跨膜电压。 假设有一个“激活功能”来控制这种相互作用。这笔赠款将通过以下方式测试这一假设：1）开发一种光学标记心脏的方法，该方法将指示记录跨膜电压的位置，2）确定电击引起的心脏细胞外电压的一阶和二阶空间导数与跨膜电压的变化，3）确定心肌结构不均匀性与电击产生的跨膜电压变化的关系，以及4）确定细胞间是否除颤过程中经常出现的缺血解偶联会改变电击产生的跨膜电压的变化。将通过跨膜电压敏感染料荧光的激光扫描仪绘图来测量兔心脏的跨膜电压变化。 为了确定心肌结构和跨膜电压变化之间的关系，我们将用激光束光学标记记录位置。 将使用透明氧化铟锡 (ITO) 和金属电击电极在一维和二维中产生电击细胞外电压的空间导数。 导数将使用金属和 ITO 记录电极进行测量。 光漂白后细胞内 6-羧基荧光素荧光恢复 (FRAP) 的图谱将表明与心肌多细胞结构相对应的细胞内扩散在控制跨膜电压变化的关系中的作用。 FRAP 还将指示缺血期间由细胞间解偶联引起的扩散常数的变化。 将确定整体缺血和缺血区域的边界是否对由冲击产生的跨膜电压变化产生解偶联影响。因此，将确定正常心脏和缺血心脏除颤期间跨膜电压变化的主要因素。 这些知识将有助于优化危及生命的心律失常的电疗法。