ten Tusscher K H W J, Noble D, Noble P J, Panfilov A V
Department of Theoretical Biology, Utrecht University, 3584 CH Utrecht, The Netherlands.
Am J Physiol Heart Circ Physiol. 2004 Apr;286(4):H1573-89. doi: 10.1152/ajpheart.00794.2003. Epub 2003 Dec 4.
The experimental and clinical possibilities for studying cardiac arrhythmias in human ventricular myocardium are very limited. Therefore, the use of alternative methods such as computer simulations is of great importance. In this article we introduce a mathematical model of the action potential of human ventricular cells that, while including a high level of electrophysiological detail, is computationally cost-effective enough to be applied in large-scale spatial simulations for the study of reentrant arrhythmias. The model is based on recent experimental data on most of the major ionic currents: the fast sodium, L-type calcium, transient outward, rapid and slow delayed rectifier, and inward rectifier currents. The model includes a basic calcium dynamics, allowing for the realistic modeling of calcium transients, calcium current inactivation, and the contraction staircase. We are able to reproduce human epicardial, endocardial, and M cell action potentials and show that differences can be explained by differences in the transient outward and slow delayed rectifier currents. Our model reproduces the experimentally observed data on action potential duration restitution, which is an important characteristic for reentrant arrhythmias. The conduction velocity restitution of our model is broader than in other models and agrees better with available data. Finally, we model the dynamics of spiral wave rotation in a two-dimensional sheet of human ventricular tissue and show that the spiral wave follows a complex meandering pattern and has a period of 265 ms. We conclude that the proposed model reproduces a variety of electrophysiological behaviors and provides a basis for studies of reentrant arrhythmias in human ventricular tissue.
研究人类心室肌心律失常的实验和临床可能性非常有限。因此,使用计算机模拟等替代方法至关重要。在本文中,我们介绍了一种人类心室细胞动作电位的数学模型,该模型虽然包含高水平的电生理细节,但在计算上具有成本效益,足以应用于大规模空间模拟以研究折返性心律失常。该模型基于最近关于大多数主要离子电流的实验数据:快速钠电流、L型钙电流、瞬时外向电流、快速和缓慢延迟整流电流以及内向整流电流。该模型包括基本的钙动力学,能够对钙瞬变、钙电流失活和收缩阶梯进行逼真的建模。我们能够重现人类心外膜、心内膜和M细胞动作电位,并表明差异可以通过瞬时外向电流和缓慢延迟整流电流的差异来解释。我们的模型重现了关于动作电位时程恢复的实验观察数据,这是折返性心律失常的一个重要特征。我们模型的传导速度恢复比其他模型更宽,并且与现有数据更吻合。最后,我们对二维人类心室组织片中螺旋波旋转的动力学进行了建模,结果表明螺旋波遵循复杂的蜿蜒模式,周期为265毫秒。我们得出结论,所提出的模型重现了多种电生理行为,并为研究人类心室组织中的折返性心律失常提供了基础。