TRANSMEMBRANE POTENTIAL MAPPING OF DEFIBRILLATION

除颤的跨膜电位图

• 批准号: 6078842
• 负责人: STEPHEN B KNISLEY
• 金额: $ 4.16万
• 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/6078842
• 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

This research will obtain fundamental knowledge of effects of electrical defibrillation shocks in the heart that is needed to understand defibrillation. Defibrillation is thought to occur in three steps: 1) The shock changes transmembrane voltages during the shock pulse. 2) The changes in transmembrane voltages alter transmembrane voltage-dependent ion channels which excite the cells or prolong action potential repolarization after the pulse. 3) The excitation or prolonged repolarization produces defibrillation. Mechanisms for the steps are not known. This project will use transmembrane voltage-sensitive dye fluorescence and a laser scanner system to study up to 127 locations on isolated arterially perfused rabbit hearts. The distributions of transmembrane voltages during the shock pulse, the excitation or prolonged repolarization after the pulse and the changes in activation patterns and block required to produce defibrillation will be determined. The maximum dV/dt of action potentials measured with microelectrodes and the sodium channel modulators, tetrodotoxin and high potassium, will be used to study transmembrane voltage-dependent fast inward sodium channel recovery during monophasic and biphasic shocks. The importance of the fast inward sodium channel recovery for the prolonged repolarization produced by the shocks will be determined. The impacts of pharmacological sodium, calcium or potassium channel blockade, present in some patients who receive shocks. on prolonged repolarization will be determined. Calcium-sensitive dye fluorescence will be measured with the laser scanner system to study the roles of ischemia, fibrillation and the transmembrane voltages during shocks in producing elevated intracellular calcium. The importance of the elevated intracellular calcium for spontaneous fibrillation induction, fibrillation maintenance and defibrillation will be determined. The project will yield insights that are necessary in order to advance understanding of cellular bases of defibrillation.

这项研究将获得有关电效应的基础知识 心脏除颤电击需要了解 除颤。除颤被认为分三个步骤进行： 1) 冲击会在冲击脉冲期间改变跨膜电压。 2) 的 跨膜电压的变化改变跨膜电压依赖性 兴奋细胞或延长动作电位的离子通道 脉冲后复极。 3) 兴奋或延长 复极产生除颤。步骤的机制不是 已知。 该项目将使用跨膜电压敏感染料荧光和 激光扫描仪系统可研究孤立动脉上多达 127 个位置 灌注兔心。跨膜电压分布 冲击脉冲、激发或长时间复极后 脉冲以及产生所需的激活模式和块的变化 将确定除颤。动作电位最大 dV/dt 用微电极和钠通道调制器测量， 河豚毒素和高钾，将用于研究跨膜 单相期间电压依赖性快速内向钠通道恢复 和双相冲击。快速内向钠通道的重要性 冲击造成的长期复极的恢复将 决定。钠、钙或钾的药理学影响 通道阻塞，存在于一些接受电击的患者中。在 将确定延长的复极。钙敏染料 将使用激光扫描仪系统测量荧光以研究 缺血、颤动和跨膜电压的作用 产生升高的细胞内钙的冲击。 的重要性 升高细胞内钙以诱导自发性颤动， 将确定颤动维持和除颤。这 项目将产生推进所必需的见解 了解除颤的细胞基础。