Fibrillation and Defibrillation

颤动和除颤

• 批准号: 7012199
• 负责人: PENG-SHENG CHEN
• 金额: $ 38.08万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-01 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7012199
• 关键词: action potentials; calcium flux; cardiovascular disorder therapy; disease /disorder model; electric countershock heart resuscitation; heart electrical activity; intracellular transport; laboratory rabbit; membrane potentials; method development; microelectrodes; myocardial infarction; myocardial ischemia /hypoxia; myocardium disorder; pathologic process; shock; single cell analysis; sudden cardiac death; tachycardia; therapy design /development; ventricular fibrillation

DESCRIPTION (provided by applicant): The objective of this grant application is to develop a rational approach to therapy of sudden cardiac death through understanding of the pathogenesis of ventricular fibrillation (VF) and electrical defibrillation at the mechanistic level. We have demonstrated that dynamic factors, such as electrical restitution and excitability, contribute to initiation and maintenance of wavebreak during VF. Alteration of these dynamic factors results in two types of VF in rabbit ventricles. The type 1 VF is associated with steep action potential duration (APD) restitution, normal excitability and multiple wavelets. Type 2 VF is associated with flat APD restitution, reduced excitability and spatiotemporal periodicity. We also developed methods to simultaneous map membrane potential (Vm) and intracellular calcium (Cai) in normal and diseased rabbit ventricles. Preliminary results suggest that Cai cycling is a critical factor that controls multiple aspects of dynamic wave stability. Furthermore, we found that Cai cycling might also play a role in the mechanisms of electrical defibrillation. Because electrical shock is the only effective therapy for VF, we propose to perform further investigations on the importance of Cai cycling in the mechanisms of ventricular defibrillation. We will use normal rabbits and rabbit models of ischemic cardiomyopathy and pacing-induced cardiomyopathy to pursue these studies. Simultaneous Vm and Cai mapping and single cell transmembrane potential recordings will be used to determine the relationship between Cai cycling, afterdepolarizations and triggered activity after defibrillation shocks. The Specific Aim 1 will test the hypothesis that Cai cycling is important in the post-shock re-initiation of Type 1 VF. The Specific Aim 2 will test the hypothesis that Cai cycling is important in the post-shock reinitiation of Type 2 VF. The Specific Aim 3 will test the hypothesis that Cai cycling is important in determining the upper limit of vulnerability. We expect that these studies will improve the understanding of the mechanisms of ventricular defibrillation and lead to better management of patients at risk of sudden cardiac death.

描述（由申请人提供）：本授予申请的目的是通过了解心室纤颤（VF）（VF）和机械水平的电脱纤纤维的理性方法来制定猝死的治疗方法。我们已经证明了动态因素（例如电恢复和兴奋性）有助于VF期间波浪破坏的启动和维护。这些动态因子的改变导致兔心室中两种类型的VF。 1型VF与陡峭的动作电位持续时间（APD）恢复，正常兴奋性和多个小波有关。 2型VF与平坦的APD恢复，降低兴奋性和时空周期性有关。我们还开发了正常和患病的兔心室中同时地图膜电位（VM）和细胞内钙（CAI）的方法。初步结果表明，CAI循环是控制动态波稳定性多个方面的关键因素。此外，我们发现CAI骑自行车也可能在电去颤纤颤的机理中发挥作用。由于电击是VF的唯一有效疗法，因此我们建议对CAI循环在心室除颤机理中的重要性进行进一步研究。我们将使用缺血性心肌病和起搏引起的心肌病的正常兔子和兔模型进行这些研究。同时的VM和CAI映射以及单细胞跨膜电势记录将用于确定Defbrillation Shocks之后的CAI循环，倒流后和触发活性之间的关系。具体目标1将检验以下假设：CAI循环在1型VF的震后重新定局很重要。具体的目标2将检验以下假设：CAI循环在2型VF的震后重新介绍很重要。具体目标3将检验以下假设：CAI循环对于确定脆弱性上限很重要。我们预计这些研究将提高对心室除颤机制的理解，并可以更好地治疗患有心脏突然死亡风险的患者。