Multi-scale Approaches to Mechanical Contraction and Electrical Wave Conduction in A 3D Model of Human Atria during Fibrillation

整合生物学的“重大挑战”之一是预测一个器官的行为，这个器官是由分子、离子、细胞和组织在多物理尺度上的综合作用产生的。心脏电生理学已经足够成熟，可以用来建立心脏的预测模型。然而，成功的心脏动力学模拟不仅需要良好验证的心脏电力学和解剖数学模型，还需要稳定有效的数值算法来求解这些多物理尺度、高度复杂和非线性的模型。该项目的目的是解决人类窦房结-心房（心脏的上部腔室）的这些挑战，其功能障碍导致发病率和死亡率。我们提出了一种具有耦合电动力学和力学动力学的新一代san -心房三维解剖模型，以及一种新的基于离散元方法的数值稳定和高效的算法。使用该模型，我们将量化药物干预对心房电和力学动力学的功能影响。这个项目的输出将是一系列新的人类san -心房计算机模型和心脏机电建模的有效数值算法。开发的模型和数值解算器将通过我们的当地研究网站和国际存储工具（www.cellML.org和www.fieldML.org）分发给公众。

One of the "grand challenges" of integrative biology is to predict the behaviour of an organ that emerges from integrated actions of molecules, ions, cells and tissues operating at multi-physical scales. Cardiac electro-physiology is sufficiently well established for developing a predictive model for the heart. However, successful simulations of cardiac dynamics requires not only well-validated mathematical model of cardiac electro-mechanics and anatomy, but also stable and efficient numerical algorithms for solving these models that are at multiple physical scales, highly complex and non-linear. The aim of this project is to tackle these challenges for human sinoatrial node - atria (SAN-atria) (the upper chambers of the heart), malfunction of that causes morbidity and mortality. We propose to develop a new generation 3D anatomical model of the SAN-atria with coupled electrical and mechanical dynamics, and a new family of numerically stable and efficient algorithms based on discrete element methods. Using the model, we shall quantify the functional impact of pharmacological interventions on atrial electrical and mechanic dynamics. The output of this project will be a family of novel computer models of human SAN-atria and efficient numerical algorithms for cardiac electro-mechanical modelling. The developed model and numerical solvers will be distributed for public access through our local research websites and international depository tools (www.cellML.org and www.fieldML.org).