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.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 (A)目标 在室颤(VF)中，心源性猝死的主要原因是 电激活分解成多波混沌状态。我们的研究主要集中在 问题是：这次破浪的原因是什么？ 传统观点认为，波是由解剖异质性造成的，例如 具有不同厚度的弯曲的室壁和隔壁，以及系统的 不同的各向异性被认为是通过心肌壁进行的。 我们早期研究的目标是回答这样的问题： 解剖学上的异质性，而不是纯粹的动力不稳定性 持续的纤颤？他们是如何互动的？ 我们现在已经证明，虽然上述解剖因素可以起到贡献作用，但 传导的动力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。 在心力衰竭中可以看到的变化。我们的具体目标是研究心脏的心律失常。 失败，尤其是未能梳理出 一方面是解剖结构异常，另一方面是细胞电生理学异常。至 研究这一点，我们将研究结构异常心脏中的正常细胞，异常细胞 在正常心脏中，然后是两种病理，细胞和组织在一起。 我们将使用由 NBCR调查人员，以及我们与NBCR研究人员合作，研究这些 问题。 具体目的1：利用兔虚拟心脏测试心脏传导功能 由于添加了诸如纤维化、梗死疤痕和细胞对细胞的损失等病理因素而产生 电气耦合。 具体目标2：使用NBCR建模环境来研究 细胞内钙处理对室颤发生和维持的影响。加州大学圣迭戈分校的电池系统 建模环境与几何模型相结合，是理想的平台 验证我们的假设，即改变细胞内钙离子的处理是导致高血压发生的关键 心力衰竭时的纤颤。 具体目标3：建立几种形式的心力衰竭的解剖模型 兔，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，测试改变的组织结构与改变的细胞的相对贡献 电生理学，在心力衰竭中心律失常的发生。 拟议的协作研究将为新的 核心的具体目标1的软件和计算方法的发展[4A.2B]， 由此产生的新的解剖和电生理网格和模型将被共享 与社区通过数据库开发的具体目标2。它将作为一个 用于测试和开发新的Bidomain模型和耦合的ODE求解器的平台 具体目标2.