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.

电除颤休克是停止心室纤颤的唯一有效疗法。 治疗的改进将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“激活功能”以控制这种相互作用。该赠款将通过1）通过1）进行光学标记心脏的方法来测试假设，该方法将指示记录跨膜电压的位置，2）确定由电击引起的心脏外电压的第一和第二空间衍生物的关系，由电击引起的细胞外电压与跨膜固定之间的变化，3）在跨膜固定之间变化，3）通过电击产生的，以及4）确定缺血（通常在除颤期间存在）是否存在细胞对细胞解偶联，从而改变电击产生的跨膜电压的变化。跨膜心脏的跨膜电压变化将通过跨膜电压敏感染料荧光的激光扫描仪映射测量。 为了确定心肌结构和跨膜电压变化之间的关系，我们将通过激光束进行光学标记记录位置。 冲击细胞外电压的空间衍生物将在一个和二维中产生透明的二键型氧化锡（ITO）和金属震动电极。 衍生物将用金属和ITO记录电极测量。 光漂白后的细胞内6-羧基氟菌素荧光恢复（FRAP）的映射将表明细胞内扩散的作用，这与心肌多细胞结构在控制跨膜电压变化的关系中相对应。 FRAP还将指示缺血期间细胞间解偶联引入的扩散常数的变化。 是否要确定全球性缺血和缺血区域的冲击产生的跨膜电压变化的脱偶联影响。因此，将确定正常和缺血性心脏在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不齐的电疗法。