THE ROLE OF ANATOMIC STRUCTURES IN VENTRICULAR FIBRILLATION

解剖结构在心室颤动中的作用

• 批准号: 8362803
• 负责人: Andrew D. McCulloch
• 金额: $ 3万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362803
• 关键词: Abnormal Cell; Anatomic Models; Anatomic structures; Anatomy; Anisotropy; Arrhythmia; Automobile Driving; Biological Models; Biomedical Computing; Calcium; Cardiac; Cell model; Cells; Cicatrix; Communities; Computer software; Computing Methodologies; Coupled; Coupling; Databases; Development; Electrophysiology (science); Environment; Fibrosis; Funding; Generations; Grant; Heart; Heart failure; Heterogeneity; Infarction; Maintenance; Modeling; Myocardial; National Center for Research Resources; Normal Cell; Oryctolagus cuniculus; Pathology; Play; Principal Investigator; Property; Relative (related person); Research; Research Infrastructure; Research Personnel; Resources; Role; Source; Structure; Testing; Thick; Tissues; United States National Institutes of Health; Ventricular; Ventricular Fibrillation; cost; sudden cardiac death; tool; virtual

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. (A) OBJECTIVES In ventricular fibrillation (VF), the leading cause of sudden cardiac death, the wave of electrical activation breaks up into a multi-wave chaotic state. Our research has focused on the question: what are the causes of this wavebreak? The traditional view was that the wave was broken up by anatomic heterogeneity, such as the curved ventricular and septal walls with their varying thicknesses, and the systematically varying anisotropy that is seen as one proceeds transmurally across the myocardial walls. The objective of our earlier research was to answer the questions: how important are anatomical heterogeneities as opposed to purely dynamical instabilities in generating and sustaining fibrillation? How do they interact? We have now shown that while the anatomic factors above can play contributory roles, the decisive role is played by the dynamical stability of conduction, which is determined by the electrophysiologic properties of the cells and tissue. We now propose to extend this research to consider the anatomic and electrophysiologic changes that are seen in heart failure. Our Specific Aims are to study arrhythmias in heart failure, and especially to tease apart the contributions to arrhythmia generation made by abnormal anatomy, on the one hand, and abnormal cell electrophysiology, on the other. To study this, we will study the normal cell in the abnormal structural heart, the abnormal cell in the normal heart and then the two pathologies, cell and tissue, together. We will use the three-dimensional ventricular anatomic models and tools developed by the NBCR investigators, and by us in conjunction with NBCR researchers, to study these questions. Specific Aim 1: To use the rabbit Virtual Heart to test the effects on cardiac wave conduction produced by adding such pathological factors as fibrosis, infarct scars, and loss of cell-to-cell electrical coupling. Specific Aim 2: To use the NBCR modeling environment to study the effects of alterations in intracellular calcium handling on the genesis and maintenance of VF. The UCSD cell systems modeling environment, coupled to the geometry models, are the ideal platforms on which to test our hypotheses that altered intracellular calcium handling is a key to the genesis of fibrillation in heart failure. Specific Aim 3: To develop anatomically realistic models of several forms of heart failure in the rabbit, and use those models together with our cell models for normal and heart failure rabbit, to test the relative contributions of altered tissue structure vs. altered cell electrophysiology, in the genesis of arrhythmias in heart failure. The proposed collaborative research will provide a driving application for the new developments in software and computational methods in Specific Aims 1 of Core [4A.2B], and the resulting new anatomic and electrophysiological meshes and models will be shared with the community via the database to be developed in Specific Aim 2. It will serve as a platform for testing and developing new bidomain models and coupled ODE solvers in Specific Aim 2.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 (一) 目标 在心室颤动（VF）（心源性猝死的主要原因）中， 电激活分解成多波混沌状态。我们的研究重点是 问题：这次浪潮的原因是什么？ 传统观点认为，波被解剖异质性所打破，例如 弯曲的心室壁和间隔壁具有不同的厚度，以及系统地 当一个人跨壁穿过心肌壁时，可以看到不同的各向异性。 我们早期研究的目的是回答以下问题： 解剖学的异质性，而不是纯粹的动态不稳定性产生和 持续性颤动？ 他们如何互动？ 我们现在已经证明，虽然上述解剖因素可以发挥贡献作用， 传导的动态稳定性起着决定性的作用，这是由 细胞和组织的电生理特性。 我们现在建议扩展这项研究以考虑解剖学和电生理学 心力衰竭中可见的变化。 我们的具体目标是研究心律失常 失败，尤其是未能梳理出对心律失常产生的贡献 一方面是解剖结构异常，另一方面是细胞电生理学异常。到 研究这个，我们将研究结构异常的心脏中的正常细胞，异常的细胞 在正常心脏中，然后将细胞和组织这两种病理状态结合在一起。 我们将使用三维心室解剖模型和工具开发 NBCR 研究人员以及我们与 NBCR 研究人员一起研究这些 问题。 具体目标1：利用兔子虚拟心脏测试对心波传导的影响 添加纤维化、梗塞疤痕、细胞间缺失等病理因素而产生 电耦合。 具体目标 2：使用 NBCR 建模环境来研究变化的影响 细胞内钙处理对 VF 发生和维持的影响。加州大学圣地亚哥分校细胞系统 与几何模型相结合的建模环境是理想的平台 检验我们的假设，即改变细胞内钙处理是发生的关键 心力衰竭中的颤动。 具体目标 3：开发几种心力衰竭的解剖学真实模型 兔子，并将这些模型与我们的细胞模型一起用于正常和心力衰竭 兔子，测试改变的组织结构与改变的细胞的相对贡献 电生理学，心力衰竭心律失常的起源。 拟议的合作研究将为新的技术提供驱动应用 核心 [4A.2B] 的特定目标 1 中软件和计算方法的发展， 由此产生的新的解剖学和电生理学网格和模型将被共享 通过将在具体目标 2 中开发的数据库与社区进行交流。它将作为 用于测试和开发新双域模型和耦合 ODE 求解器的平台 具体目标2。