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

复杂的时空动力学是许多心脏疾病的基础。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，诱导和维持这些心律失常的机制仍然难以捉摸。我们寻求提高我们对这些机制的基本理解，通过开发一个激进的和迫切需要的范式转变，从计算密集型直接数值模拟到描述心脏动力学的时空模式的有限剧目。使用尖端的数值算法，我们将计算一个层次的精确稳定和时间周期的解决方案的详细离子模型的心脏动力学。这些不稳定的解决方案描述心脏动力学的有限的剧目的时空模式，目前隐藏的视图。他们的决心完全解决心脏组织模型是计算密集型的，但一旦这些解决方案得到，他们产生一个全新的理解时空混沌动力学作为一个步行通过相应的经常性模式的剧目。该表示还允许使用可能需要比当前除颤方法更低的电压的电刺激来开发心脏动力学的非线性控制。数值计算将与涉及心脏组织和细胞培养的实验紧密结合。实验将被用来验证所提出的计算分析和测试的控制approximates.Cardiac心律失常是一个主要的原因死亡率在工业化的世界，和任何减少其发病率从他们的行为更深入的了解可能会有重大的社会影响。通过结合最先进的数值，分析和实验方法来研究心脏组织，该项目旨在启动一个根本的范式转变：我们建议使用直接数值模拟作为工具，开发一种新的定量模板描述的心脏组织的动力学。在这种方法中，心律失常的动力学被理解为不同心律之间的一组可能的转变，不仅导致对心律失常的开始和演变的更深入的动力学理解，而且还导致对其预防或终止的改进策略。虽然重点是心脏动力学，开发的方法将影响其他领域处理高维复杂系统，表现出不稳定的复发模式，如神经疾病，流体和等离子体的动力学和气候研究。

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.