Collaborative Research: CDI Type II: Dynamics and Control of Cardiac Tissue

合作研究：CDI II 型：心脏组织的动力学和控制

• 批准号: 1341128
• 负责人: Flavio Fenton
• 金额: $ 54.68万
• 依托单位: Georgia Tech Research Corporation
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-13 至 2016-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1341128&HistoricalAwards=false
• 关键词: Collaborative; Research; CDI; Type; II

Complex spatiotemporal dynamics underlie many arrhythmic disorders of the heart. Despite decades of biomedical research and the development of increasingly detailed computational models, the mechanisms that induce and sustain these arrhythmias remain elusive. We seek to improve our fundamental understanding of these mechanisms by developing a radical and urgently needed paradigm shift from computationally intensive direct numerical simulations to a description of cardiac dynamics in terms of a finite repertoire of spatiotemporal patterns. Using cutting-edge numerical algorithms, we will compute a hierarchy of exact steady and time-periodic solutions of detailed ionic models of cardiac dynamics. These unstable solutions describe cardiac dynamics in terms of a finite repertoire of spatiotemporal patterns that are currently hidden from view. Their determination for fully resolved cardiac tissue models is computationally intensive, but once these solutions are obtained, they yield a radically new understanding of the spatiotemporally chaotic dynamics as a walk through a repertoire of corresponding recurrent patterns. This representation also allows development of nonlinear control of cardiac dynamics using electrical stimulation that may require lower voltages than current defibrillation approaches. Numerical computations will be tightly integrated with experiments involving both cardiac tissue and cell cultures. The experiments will be used both to validate the proposed computational analysis and to test the control approach.Cardiac arrhythmias are a major cause of mortality in the industrialized world, and any reduction in their incidence derived from a deeper understanding of their behavior could have a significant societal impact. By combining state-of-the-art numerical, analytical, and experimental approaches to the study of cardiac tissue, this project aims to initiate a radical paradigm shift: we propose to use direct numerical simulation as a tool to develop a new kind of quantitative template description of the dynamics of cardiac tissue. In this approach, the dynamics of arrhythmias is understood as a set of possible transitions between different cardiac rhythms, leading not only to a deeper dynamical understanding of the initiation and evolution of cardiac arrhythmias, but also to improved strategies for their prevention or termination. Although the focus is on cardiac dynamics, the methods developed will impact other fields dealing with high-dimensional complex systems that exhibit unstable recurrent patterns, such as neural disorders, dynamics of fluids and plasmas, and climate studies.

复杂的时空动力学是许多心脏心律失常的基础。尽管数十年的生物医学研究和越来越详细的计算模型的发展，但诱导和维持这些心律不齐的机制仍然难以捉摸。我们试图通过开发从计算密集的直接数值模拟到对心脏动力学的描述，从时空模式的有限曲目来描述心脏动力学的描述，从而提高对这些机制的基本理解。使用尖端的数值算法，我们将计算心脏动力学详细离子模型的精确稳定和时间周期溶液的层次结构。这些不稳定的解决方案用有限的时空模式曲目来描述心脏动力学，这些曲线目前隐藏了时空模式。它们对完全分辨的心脏组织模型的确定是计算密集的，但是一旦获得了这些解决方案，它们就会对时空混乱的动力学产生一定的新理解，因为它穿越了相应的经常性模式的曲目。该表示还允许使用电刺激来开发非线性对心脏动力学的控制，这可能比电流除颤方法较低。数值计算将与涉及心脏组织和细胞培养物的实验紧密整合。这些实验将既可以验证提出的计算分析又测试控制方法。心律不齐是工业化世界中死亡率的主要原因，并且从对其行为的更深入了解可能会产生重大的社会影响。通过结合对心脏组织研究的最新数值，分析和实验方法，该项目旨在启动自由基范式转移：我们建议使用直接数值模拟作为一种工具来开发一种新型的定量模板对心脏组织动力学的描述。在这种方法中，心律不齐的动力学被理解为不同心律之间的一组可能的过渡，不仅导致对心律不齐的起始和进化的更深入的动态理解，而且还可以改善其预防或终止的策略。尽管重点是心脏动力学，但开发的方法将影响与高维复合系统相关的其他领域，这些系统表现出不稳定的复发模式，例如神经疾病，流体和等离子体的动态以及气候研究。