TRANSMEMBRANE POTENTIAL MAPPING OF DEFIBRILLATION

除颤的跨膜电位图

• 批准号: 6430832
• 负责人: STEPHEN B KNISLEY
• 金额: $ 10.76万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 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 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6430832
• 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.

这项研究将获得基本知识的影响，电 心脏除颤电击，这是需要了解 除颤除颤被认为分三个步骤发生：1） 电击在电击脉冲期间改变跨膜电压。2)的 跨膜电压的变化改变了跨膜电压依赖性 激发细胞或延长动作电位的离子通道 脉冲后复极化。3)兴奋或延长 复极化产生除颤。步骤的机制不是 知道的 本项目将使用跨膜电压敏感染料荧光和 激光扫描仪系统，用于研究孤立动脉上多达127个位置， 灌注的兔子心脏跨膜电压的分布 电击脉冲，兴奋或延长复极化后， 脉冲和激活模式的变化和块所需的生产 将确定除颤。动作电位的最大dV/dt 用微电极和钠通道调节剂测量， 河豚毒素和高钾，将用于研究跨膜 电压依赖性快内向钠通道恢复 和双相电击。快速钠离子通道的重要性 恢复的长期复极所产生的冲击将是 测定药理学钠、钙或钾的影响 通道阻滞，存在于一些接受电击的患者中。对 将确定延长的复极化。钙敏染料 将用激光扫描仪系统测量荧光，以研究 缺血、纤维性颤动和跨膜电压的作用 休克产生升高的细胞内钙。 的重要性 升高的细胞内钙用于自发性纤维性颤动诱导， 将确定纤颤维持和除颤。的 项目将产生必要的见解，以促进 了解除颤的细胞基础。