Cardiac Fibrillation: Mechanisms and Therapy

心脏颤动：机制和治疗

• 批准号: 7256521
• 负责人: James N Weiss
• 金额: $ 197万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-10 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7256521
• 关键词: Cardiac; Fibrillation; Mechanisms; Therapy

DESCRIPTION (provided by applicant): Ventricular fibrillation (VF) is the most common cause of sudden death, accounting for over 300,000 deaths annually in the US alone. The objective of this proposed Program Project is to develop a rational approach to the therapy of sudden cardiac death (SCO) through understanding the pathogenesis of VF at the mechanistic level. The proposal represents a continuation of our efforts, which began with our SCOR in Sudden Cardiac Death in 1995, to address this objective by combining mathematical biology with experimental biology to integrate information at the molecular, cellular, tissue and systems levels. The theme of this proposed Program Project is that dynamic wave instability (regulated by electrical restitution, intracellular Cai cycling, cardiac memory and diffusive currents) interacts synergistically with increased electrical and structural tissue heterogeneity in the diseased heart to increase the risk of VF and SCO, and that by developing molecular interventions designed to decrease dynamic wave instability, VF and SCO can be prevented. The four projects and three cores will address this theme using experimental approaches including patch clamping, optical mapping with fluorescent dyes, molecular biology, adenoviral gene transfer, and theoretical approaches including mathematical modeling, computer simulations and nonlinear dynamics. Studies ranging from isolated myocytes to intact normal and diseased ventricles, both in vivo and in silico, will be conducted interactively through this Program Project to evaluate comprehensively dynamic factors controlling wave stability as therapeutic targets for prevention of VF and SCO.

描述（由申请人提供）：心室纤颤（VF）是猝死的最常见原因，仅在美国，每年就会占300,000多次死亡。该提议的计划项目的目的是通过了解机械水平上VF的发病机理来开发一种理性的心脏死亡（SCO）治疗方法。该提议代表了我们的努力的延续，这始于我们的SCOR 1995年的心脏死亡猝死，通过将数学生物学与实验生物学相结合，以整合分子，细胞，组织和系统水平的信息来解决这一目标。这个提出的计划项目的主题是，动态波不稳定性（受电恢复，细胞​​内CAI循环，心脏记忆和扩散电流的调节）与患病心脏中的电和结构组织异质性的增加相互作用，以增加VF和SCO的风险，从而促进分子式介绍的动力学能力，并降低了动力学的能力。这四个项目和三个核心将使用实验方法来解决此主题，包括贴片夹具，荧光染料的光学映射，分子生物学，腺病毒基因转移以及理论方法以及包括数学建模，计算机模拟和非线性动态的理论方法。从孤立的心肌细胞到完整的正常和患病的心室的研究，无论是在体内还是在计算机中，都将通过该程序项目进行交互性进行，以评估控制波稳定性的全面动态因子，以控制波浪稳定性作为预防VF和SCO的治疗目标。