Xia Ling, Zhang Yu, Zhang Henggui, Wei Qing, Liu Feng, Crozier Stuart
Department of Biomedical Engineering, Zhejiang University, Hangzhou 310027, People's Republic of China.
Physiol Meas. 2006 Nov;27(11):1125-42. doi: 10.1088/0967-3334/27/11/006. Epub 2006 Sep 18.
Brugada syndrome (BS) is a genetic disease identified by an abnormal electrocardiogram (ECG) (mainly abnormal ECGs associated with right bundle branch block and ST-elevation in right precordial leads). BS can lead to increased risk of sudden cardiac death. Experimental studies on human ventricular myocardium with BS have been limited due to difficulties in obtaining data. Thus, the use of computer simulation is an important alternative. Most previous BS simulations were based on animal heart cell models. However, due to species differences, the use of human heart cell models, especially a model with three-dimensional whole-heart anatomical structure, is needed. In this study, we developed a model of the human ventricular action potential (AP) based on refining the ten Tusscher et al (2004 Am. J. Physiol. Heart Circ. Physiol. 286 H1573-89) model to incorporate newly available experimental data of some major ionic currents of human ventricular myocytes. These modified channels include the L-type calcium current (I(CaL)), fast sodium current (I(Na)), transient outward potassium current (I(to)), rapidly and slowly delayed rectifier potassium currents (I(Kr) and I(Ks)) and inward rectifier potassium current (I(Ki)). Transmural heterogeneity of APs for epicardial, endocardial and mid-myocardial (M) cells was simulated by varying the maximum conductance of I(Ks) and I(to). The modified AP models were then used to simulate the effects of BS on cellular AP and body surface potentials using a three-dimensional dynamic heart-torso model. Our main findings are as follows. (1) BS has little effect on the AP of endocardial or mid-myocardial cells, but has a large impact on the AP of epicardial cells. (2) A likely region of BS with abnormal cell AP is near the right ventricular outflow track, and the resulting ST-segment elevation is located in the median precordium area. These simulation results are consistent with experimental findings reported in the literature. The model can reproduce a variety of electrophysiological behaviors and provides a good basis for understanding the genesis of abnormal ECG under the condition of BS disease.
Brugada综合征（BS）是一种通过异常心电图（ECG）（主要是与右束支传导阻滞及右胸前导联ST段抬高相关的异常心电图）识别出的遗传性疾病。BS会导致心脏性猝死风险增加。由于获取数据存在困难，针对患有BS的人体心室肌的实验研究一直有限。因此，使用计算机模拟是一种重要的替代方法。此前大多数BS模拟是基于动物心脏细胞模型。然而，由于物种差异，需要使用人体心脏细胞模型，尤其是具有三维全心脏解剖结构的模型。在本研究中，我们基于对Ten Tusscher等人（2004年，《美国生理学杂志：心脏循环生理学》286卷，H1573 - 89页）的模型进行改进，纳入了人体心室肌细胞一些主要离子电流的最新实验数据，从而开发出了人体心室动作电位（AP）模型。这些经过修改的通道包括L型钙电流（I(CaL)）、快速钠电流（I(Na)）、瞬时外向钾电流（I(to)）、快速和缓慢延迟整流钾电流（I(Kr)和I(Ks)）以及内向整流钾电流（I(Ki)）。通过改变I(Ks)和I(to)的最大电导率，模拟了心外膜、心内膜和心肌中层（M）细胞动作电位的跨壁异质性。然后使用三维动态心脏 - 躯干模型，将经过修改的动作电位模型用于模拟BS对细胞动作电位和体表电位的影响。我们的主要研究结果如下：（1）BS对心内膜或心肌中层细胞的动作电位影响较小，但对心外膜细胞的动作电位影响较大。（2）动作电位异常的BS可能区域靠近右心室流出道，由此产生的ST段抬高位于胸前区中部。这些模拟结果与文献中报道的实验结果一致。该模型能够重现多种电生理行为，为理解BS疾病状态下异常心电图的发生机制提供了良好的基础。
