Spiral Wave Initiation in an Electromechanical Model for Human Cardiac Tissue

在工业化世界中，心律失常引起的心力衰竭是主要的死亡原因。危险类型的心律失常是由心肌电活动的螺旋波引起的。因此，了解心脏中螺旋波的激发机制是心脏病学的一项主要任务。以往关于心脏中螺旋波激发的理论研究大多没有考虑心脏的变形，尽管心脏的机械活动被证明对电过程有很大的影响。在我的博士论文中，我发展了一个新的建模框架来研究心脏组织的机电活动。它将心脏兴奋的简化模型与心脏弹性的离散力学描述结合在一起。该模型为研究心脏组织中机电过程的一般性质提供了一个有效的数值框架。我用这种方法系统地研究了由于心脏的电和机械过程的复杂耦合而产生的螺旋波启动的基本机制。这项研究带来了有希望的结果：我能够识别出心脏中可能发生的五种螺旋形成机制。以前工作的一个限制是，我的方法没有详细描述心肌细胞的离子电流及其张力发展过程，而是使用了一般性的描述。因此，我已经开始开发一种新的模型，将我的高效离散力学模型结合到人类心脏兴奋和兴奋-收缩耦合的生物物理模型中。本项目的目的是使用我的新方法，确定先前发现的螺旋波启动机制中哪些与人类心脏组织相关，并识别新的心律失常发生的生物物理机制。首先，初步结果表明，很可能会发现这样的新机制。我最近的模拟显示，心脏的变形可能会促进动态不稳定--心脏交替--这在实验、建模甚至临床工作中都被认为是心律失常发作的预测因子。

Heart failure due to cardiac arrhythmias is a major cause of death in the industrialized world. Dangerous types of arrhythmia are caused by spiral waves of electrical activity in the cardiac muscle. Therefore, it is a major task in cardiology to understand mechanisms of spiral wave initiation in the heart.Most previous theoretical studies on spiral wave initiation in the heart did not take the deformation of the heart into account; albeit, the mechanical activity of the heart has been shown to greatly affect the electrical processes.In my PhD thesis I have developed a new modeling framework to study electromechanical activity of cardiac tissue. It couples a simplified model for cardiac excitation with a discrete mechanical description of cardiac elasticity. This model provides an efficient numerical framework to study generic properties of electromechanical processes in cardiac tissue. I used the method to systematically study the basic mechanisms of spiral wave initiation that emerge as a consequence of the complex coupling of the electrical and mechanical processes in the heart. This research delivered promising results: I was able to identify five mechanisms of spiral formation that could occur in the heart.A limitation of that previous work is that my approach does not describe the ionic currents of a cardiac cell and its processes of tension development in detail, but rather employs a generic description. Therefore, I have started to develop of a new model which combines my efficient discrete mechanics model to biophysical models of human cardiac excitation and excitation-contraction coupling.The aim of this project is to use my new approach and determine which of the previously found mechanisms for spiral wave initiation are relevant for human cardiac tissue, and also, identification of new biophysical mechanisms of onset of cardiac arrhythmias. First preliminary results indicate that such new mechanisms are likely to be found. My recent simulations showed that deformation of the heart may promote dynamical instabilities - cardiac alternans - which are considered in experimental, modeling and even clinical work, as predictors for the onset of arrhythmias.