论文标题

多尺度心脏活动力学的生物物理详细数学模型

Biophysically detailed mathematical models of multiscale cardiac active mechanics

论文作者

Regazzoni, Francesco, Dedè, Luca, Quarteroni, Alfio

论文摘要

我们提出了四个新型的数学模型,描述了心肌组织中力产生的微观机制,这些机制适用于心脏机电的多尺度数值模拟。这样的模型基于肉瘤中调节和收缩蛋白的生物物理准确表示。我们的模型与文献中可用的大多数肌节动力学模型不同,并且具有可比的细节丰富性,不需要耗时的蒙特卡洛方法来进行数值近似。相反,我们提出的模型仅需要解决PDE和/或ODES系统(仅涉及20个ODE的四个中的最少的模型),从而带有显着的计算效率。通过关注两个模型,这些模型以描述的详细信息和参数可识别性之间的最佳权衡,我们提出了一条管道,以从文献中可用的实验测量开始校准此类参数。多亏了这条管道,我们将这些模型校准用于室温大鼠和身体温度的人类细胞。我们通过数值模拟显示,提出的模型正确预测了力产生的主要特征,包括稳态力量 - 钙和力量长度关系,抽搐的长度依赖性延长和峰值力的增加,力 - 效率关系。此外,当在心脏机电的多尺度3D数值模拟中使用时,它们可以正确地重现坦率的延伸效果。

We propose four novel mathematical models, describing the microscopic mechanisms of force generation in the cardiac muscle tissue, which are suitable for multiscale numerical simulations of cardiac electromechanics. Such models are based on a biophysically accurate representation of the regulatory and contractile proteins in the sarcomeres. Our models, unlike most of the sarcomere dynamics models that are available in the literature and that feature a comparable richness of detail, do not require the time-consuming Monte Carlo method for their numerical approximation. Conversely, the models that we propose only require the solution of a system of PDEs and/or ODEs (the most reduced of the four only involving 20 ODEs), thus entailing a significant computational efficiency. By focusing on the two models that feature the best trade-off between detail of description and identifiability of parameters, we propose a pipeline to calibrate such parameters starting from experimental measurements available in literature. Thanks to this pipeline, we calibrate these models for room-temperature rat and for body-temperature human cells. We show, by means of numerical simulations, that the proposed models correctly predict the main features of force generation, including the steady-state force-calcium and force-length relationships, the length-dependent prolongation of twitches and increase of peak force, the force-velocity relationship. Moreover, they correctly reproduce the Frank-Starling effect, when employed in multiscale 3D numerical simulation of cardiac electromechanics.

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