Bueno-Orovio Alfonso, Cherry Elizabeth M, Fenton Flavio H
Departamento de Matemáticas, Universidad de Castilla-La Mancha, Ciudad Real, Spain.
J Theor Biol. 2008 Aug 7;253(3):544-60. doi: 10.1016/j.jtbi.2008.03.029. Epub 2008 Apr 8.
Modeling the dynamics of wave propagation in human ventricular tissue and studying wave stability require models that reproduce realistic characteristics in tissue. We present a minimal ventricular (MV) human model that is designed to reproduce important tissue-level characteristics of epicardial, endocardial and midmyocardial cells, including action potential (AP) amplitudes and morphologies, upstroke velocities, steady-state action potential duration (APD) and conduction velocity (CV) restitution curves, minimum APD, and minimum diastolic interval. The model is then compared with three previously published human ventricular cell models, the Priebe and Beuckelmann (PB), the Ten Tusscher-Noble-Noble-Panfilov (TNNP), and the Iyer-Mazhari-Winslow (IMW). For the first time, the stability of reentrant waves for all four models is analyzed, and quantitative comparisons are made among the models in single cells and in tissue. The PB, TNNP, and IMW models exhibit quantitative differences in APD and CV rate adaptation, as well as completely different reentrant wave dynamics of quasi-breakup, stability, and breakup, respectively. All the models have dominant frequencies comparable to clinical values except for the IMW model, which has a large range of frequencies extending beyond the clinical range for both ventricular tachycardia (VT) and ventricular fibrillation (VF). The TNNP and IMW models possess a large degree of short-term memory and we show for the first time the existence of memory in CV restitution. The MV model also can be fitted to reproduce the dynamics of other models and is computationally more efficient: the times required to simulate the MV, TNNP, PB and IMW models follow the ratio 1:31:50:8084.
模拟人体心室组织中的波传播动力学并研究波的稳定性,需要能够再现组织中真实特征的模型。我们提出了一种最小心室(MV)人体模型,该模型旨在再现心外膜、心内膜和心肌中层细胞的重要组织水平特征,包括动作电位(AP)幅度和形态、上升速度、稳态动作电位持续时间(APD)和传导速度(CV)恢复曲线、最小APD和最小舒张间期。然后将该模型与之前发表的三种人体心室细胞模型进行比较,即普里布和博伊克尔曼(PB)模型、滕·图斯彻 - 诺布尔 - 诺布尔 - 潘菲洛夫(TNNP)模型和伊耶 - 马扎里 - 温斯洛(IMW)模型。首次分析了所有四个模型的折返波稳定性,并在单细胞和组织层面上对模型进行了定量比较。PB模型、TNNP模型和IMW模型在APD和CV速率适应性方面表现出定量差异,并且分别具有完全不同的准破裂、稳定和破裂的折返波动力学。除IMW模型外,所有模型的主导频率都与临床值相当,IMW模型具有大范围的频率,超出了室性心动过速(VT)和室性颤动(VF)临床范围。TNNP模型和IMW模型具有很大程度的短期记忆,我们首次证明了CV恢复中存在记忆。MV模型还可以进行拟合以再现其他模型的动力学,并且计算效率更高:模拟MV模型、TNNP模型、PB模型和IMW模型所需的时间之比为1:31:50:8084。