论文标题
动作电位传播和与心肌成纤维细胞偶联的心房组织模型中的阻塞
Action potential propagation and block in a model of atrial tissue with myocyte-fibroblast coupling
论文作者
论文摘要
心肌细胞和成纤维细胞之间的电耦合以及心肌组织中成纤维细胞的空间分布是触发和维持心律不齐的重要因素,但其作用知之甚少。本文介绍了直接数值模拟和与肌细胞成纤维细胞偶联的房组织模型中传播的渐近理论和电激发的块。特别是引入了三个理想化的成纤维细胞分布:均匀分布,成纤维细胞屏障和心肌细胞海峡,所有这些分布都被认为是逼真的成纤维细胞分布的组成块。在所有情况下,从直接模拟中估算了包括传导速度,峰值电位和三角测量指数在内的主要动作潜力生物标志物。发现传播块在定义每个理想化成纤维细胞分布的参数的某些临界值下发生,并准确确定这些临界值。早先提出的渐近理论扩展并应用于均匀的成纤维细胞分布的情况。生物标志物值是从耦合的快速时间和缓慢的周期性边界价值问题的杂交分析数字解决方案中获得的,并与直接数值模拟进行了很好的比较。绝对折射率的边界仅由快速问题决定,并被发现取决于肌细胞电位的值以及在传播脉冲之前的钠电流的慢速灭活变量。反过来,这些数量是通过常规扰动扩展从缓慢的问题中估算出来的,以找到耦合的心肌细胞纤维细胞动力学的稳态。渐近理论给出了一种简单的分析表达,在成纤维细胞存在下以显着准确的繁殖范围捕获。
The electrical coupling between myocytes and fibroblasts and the spacial distribution of fibroblasts within myocardial tissues are significant factors in triggering and sustaining cardiac arrhythmias but their roles are poorly understood. This article describes both direct numerical simulations and an asymptotic theory of propagation and block of electrical excitation in a model of atrial tissue with myocyte-fibroblast coupling. In particular, three idealised fibroblast distributions are introduced: uniform distribution, fibroblast barrier and myocyte strait, all believed to be constituent blocks of realistic fibroblast distributions. Primary action potential biomarkers including conduction velocity, peak potential and triangulation index are estimated from direct simulations in all cases. Propagation block is found to occur at certain critical values of the parameters defining each idealised fibroblast distribution and these critical values are accurately determined. An asymptotic theory proposed earlier is extended and applied to the case of a uniform fibroblast distribution. Biomarker values are obtained from hybrid analytical-numerical solutions of coupled fast-time and slow-time periodic boundary value problems and compare well to direct numerical simulations. The boundary of absolute refractoriness is determined solely by the fast-time problem and is found to depend on the values of the myocyte potential and on the slow inactivation variable of the sodium current ahead of the propagating pulse. In turn, these quantities are estimated from the slow-time problem using a regular perturbation expansion to find the steady state of the coupled myocyte-fibroblast kinetics. The asymptotic theory gives a simple analytical expression that captures with remarkable accuracy the block of propagation in the presence of fibroblasts.