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）：本拨款申请的目的是通过在机械层面上了解心室颤动 (VF) 和电除颤的发病机制，开发一种合理的心源性猝死治疗方法。我们已经证明，动态因素（例如电恢复和兴奋性）有助于室颤期间波破裂的启动和维持。这些动态因素的改变导致兔心室出现两种类型的室颤。 1 型室颤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相关。 2 型 VF 与 APD 恢复平坦、兴奋性降低和时空周期性相关。我们还开发了同时绘制正常和患病兔心室膜电位 (Vm) 和细胞内钙 (Cai) 的方法。初步结果表明，蔡循环是控制动态波浪稳定性多个方面的关键因素。此外，我们发现蔡循环也可能在电除颤机制中发挥作用。由于电击是治疗 VF 的唯一有效方法，因此我们建议进一步研究蔡循环在心室除颤机制中的重要性。我们将使用正常兔子以及缺血性心肌病和起搏性心肌病的兔子模型来进行这些研究。同时 Vm 和 Cai 绘图以及单细胞跨膜电位记录将用于确定 Cai 循环、后除极和除颤电击后触发活动之间的关系。具体目标 1 将检验 Cai 循环在 1 型 VF 电击后重新启动中发挥重要作用的假设。具体目标 2 将检验 Cai 循环在 2 型 VF 电击后重新启动中发挥重要作用的假设。具体目标 3 将检验蔡循环对于确定脆弱性上限很重要的假设。我们期望这些研究将增进对心室除颤机制的理解，并更好地管理有心源性猝死风险的患者。