Model of Anisotropic Reverse Cardiac Growth in Mechanical Dyssynchrony
Model of Anisotropic Reverse Cardiac Growth in Mechanical Dyssynchrony
复制标题
DOI：
10.1038/s41598-019-48670-8
复制
发表时间：
2019-09-03
影响因子：
4.6
通讯作者：
Lee, Lik Chuan
中科院分区：
文献类型：
--
作者：
Arumugam, Jayayel;Mojumder, Joy;Lee, Lik Chuan
基于最近的单细胞实验表明，纵向肌细胞拉伸产生并行和串行添加的肌节，我们开发了一个各向异性的生长本构模型与弹性肌纤维拉伸作为生长刺激，以模拟长期的变化，在双心室的几何形状与心脏电力学的改变。本构模型是基于体积增长框架。在该模型中，局部的生长演变的肌细胞的纵向和横向方向的驱动的最大弹性肌纤维拉伸在一个心动周期从其相应的局部稳态设定点的偏差，但具有不同的灵敏度。局部稳态设定点由具有正常激活模式的模拟确定。生长本构模型耦合到一个机电模型和校准的基础上，全球和局部心室的几何变化与慢性左心室游离壁起搏在以前的动物实验中发现。我们发现，耦合的机电生长模型可以定量地再现以下内容：（1）薄和增厚的心室壁分别在早期和晚期激活区和（2）整体左心室扩张实验测量。这些发现加强了弹性肌纤维拉伸在细胞水平和组织水平上作为生长刺激剂的作用。
Based on recent single-cell experiments showing that longitudinal myocyte stretch produces both parallel and serial addition of sarcomeres, we developed an anisotropic growth constitutive model with elastic myofiber stretch as the growth stimuli to simulate long-term changes in biventricular geometry associated with alterations in cardiac electromechanics. The constitutive model is developed based on the volumetric growth framework. In the model, local growth evolutions of the myocyte's longitudinal and transverse directions are driven by the deviations of maximum elastic myofiber stretch over a cardiac cycle from its corresponding local homeostatic set point, but with different sensitivities. Local homeostatic set point is determined from a simulation with normal activation pattern. The growth constitutive model is coupled to an electromechanics model and calibrated based on both global and local ventricular geometrical changes associated with chronic left ventricular free wall pacing found in previous animal experiments. We show that the coupled electromechanics-growth model can quantitatively reproduce the following: (1) Thinning and thickening of the ventricular wall respectively at early and late activated regions and (2) Global left ventricular dilation as measured in experiments. These findings reinforce the role of elastic myofiber stretch as a growth stimulant at both cellular level and tissue-level.