中层心肌细胞分布与长QT综合征中折返激动发生机制的计算机仿真研究

中层心肌 (M)细胞的分布是决定心室不应期空间分布的重要参数。特定离子通道的基因突变是产生遗传性长QT综合征的基础。但在离子通道水平上对M细胞分布状态与长QT综合征中尖端扭转型室性心动过速 (Tdp)折返机制关系的理论研究甚少。用Luo Rudy心室肌细胞动作电位模型LRd0 0进行二维心室肌组织仿真研究。采用特定M细胞岛形分布观察心室激动的跨壁传播特点。通过设置快速延迟整流钾电流 (IKr)通道的电导为零 ,模拟动物实验中灌注d sotalol阻断IKr形成LQT2模型 ,并在四种仿真条件下观察复极跨壁异质性的特征。在LQT2模型中 ,动作电位的时程延长 ,复极跨壁分布的最大值从对照条件下的 1 5ms/mm延长至 2 5ms/mm ,提示动作电位跨壁复极离散度增大。在LQT2模型中 ,M细胞岛形分布形状对不应期的空间分布起着重要的决定性作用。传导阻滞、Tdp形成、以及壁内折返环的维持均与M细胞的分布形状有关。结论 :M细胞的特征分布是产生不应期在空间上异质性的基础。不应期的局部延长是产生功能性折返的基础。在长QT综合征中 ,M细胞的特征分布对Tdp的折返形成起着重要的作用

A Computer Simulation Study on the Relation of the Dispersion of M Cells and Reentrant Action in the Long-QT Syndromes

M cells play a dominant role in the spatial dispersion of refractoriness. Specific ion channel mutations underline the congenital long QT syndrome (LQTS). But there are few theoretic studies on the relationship between the dispersion of M cells and the reentrant mechanisms of Torsade de Pointes in the long QT syndrome at the ionic channel level. The Luo Rudy models (LRd00) of mammalian ventricular cell were used in simulating of two dimensional (2 D) ventricular tissue. The specific dispersion of M cells was used in the study of the transmural spread of action potential. LQT2 model was achieved by setting the maximum conductance of the I Kr channel to zero. This simulated the surrogate model of LQT2 in perfusion with d sotalo (I Kr blockader) in animal experiments. The transmural heterogeneities of repolarization were studied on four different simulate conditions. The duration of action potential was prolonged in LQT2 model, and the transmural dispersion of repolarization (DOR) abrupt rose to 25ms/mm (LQT2) from 15ms/mm (controls). The shape of M cells dispersion was related with the spatial dispersion of refractory. In the processing of induced Tdp the shape of M cells dispersion was related with conduction block and intramural reentrant circuits. Conclusions: The specific dispersion of M cells is the substrate of spatial heterogeneitic dispersion of refractory. Partially prolonging of refractory is the base of functional reentry. The specific dispersion of M cells plays an important role in forming of reentrant of Torsade de Pointes in the long QT syndromes