Background

Cardiovascular diseases are the top killer of human beings. The ventricular arrhythmia, as a type of malignant cardiac arrhythmias, typically leads to death if not treated within minutes. The multi-scale virtual heart provides an idealized tool for exploring the underlying mechanisms, by means of incorporating abundant experimental data at the level of ion channels and analyzing the subsequent pathological changes at organ levels. However, there are few studies on building a virtual heart model for rats—a species most widely used in experiments.

Objective

To build a multi-scale computational model for rats, with detailed methodology for the model construction, computational optimization, and its applications.

Methods

First, approaches for building multi-scale models ranging from cellular to 3-D organ levels are introduced, with detailed descriptions of handling the ventricular myocardium heterogeneity, geometry processing, and boundary conditions, etc. Next, for dealing with the expensive computational costs of 3-D models, optimization approaches including an optimized representation and a GPU-based parallelization method are introduced. Finally, methods for reproducing of some key phenomenon (e.g., electrocardiograph, spiral/scroll waves) are demonstrated.

Results

Three types of heterogeneity, including the transmural heterogeneity, the interventricular heterogeneity, and the base-apex heterogeneity are incorporated into the model. The normal and reentrant excitation waves, as well as the corresponding pseudo-ECGs are reproduced by the constructed ventricle model. In addition, the temporal and spatial vulnerability to reentry arrhythmias are quantified based on the evaluation experiments of vulnerable window and the critical length.

Conclusions

The constructed multi-scale rat ventricle model is able to reproduce both the physiological and the pathological phenomenon in different scales. Evaluation experiments suggest that the apex is the most susceptible area to arrhythmias. The model can be a promising tool for the investigation of arrhythmogenesis and the screening of anti-arrhythmic drugs.

中文翻译：

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大鼠心室的多尺度计算模型：构建、并行化和应用

背景

心血管疾病是人类的头号杀手。室性心律失常作为恶性心律失常的一种，如果在几分钟内不进行治疗，通常会导致死亡。多尺度虚拟心脏通过在离子通道水平结合丰富的实验数据并在器官水平分析随后的病理变化，为探索潜在机制提供了理想化的工具。然而，很少有关于为老鼠建立虚拟心脏模型的研究——老鼠是实验中使用最广泛的物种。

客观的

建立大鼠多尺度计算模型，详细介绍模型构建、计算优化及其应用的方法论。

方法

首先，介绍了构建从细胞到 3-D 器官水平的多尺度模型的方法，详细描述了处理心室心肌异质性、几何处理和边界条件等。接下来，处理昂贵的计算成本介绍了 3-D 模型、优化方法，包括优化表示和基于 GPU 的并行化方法。最后，演示了一些关键现象（例如，心电图、螺旋/滚动波）的再现方法。

结果

模型中包含三种类型的异质性，包括透壁异质性、室间异质性和基尖异质性。正常和折返激发波，以及相应的伪心电图由构建的心室模型再现。此外，基于易损窗口和临界长度的评估实验，量化了折返性心律失常的时空易损性。

结论

构建的多尺度大鼠心室模型能够同时再现不同尺度的生理和病理现象。评估实验表明心尖部是最易发生心律失常的区域。该模型可以成为研究心律失常和筛选抗心律失常药物的有前途的工具。