Fig. 6 Membrane voltage heterogeneity(δV) and the spatial gradient of APD90across the 1D strand (a-d) Membrane voltage heterogeneity (δV) between single ENDO, MIDDLE, and EPI cells in the WT, N588K, low and high doses of propafenone conditions, respectively. (e) MaximalδVduring repolarization process between ENDO-EPI cells. (f) Spatial distribution of APD90across the 1D transmural ventricular strand model. (g-i) The spatial gradient of APD90across the 1D strand in the N588K, low and high doses of propafenone conditions. (j) The maximal spatial gradient of APD90.
3 结论
本文通过计算机仿真构建了人体心室细胞和组织药物作用模型,利用该模型,建立了普罗帕酮作用于SQTS过程中微观AP变化与宏观ECG之间的联系,从亚细胞、细胞、组织三个尺度,模拟了SQTS下的普罗帕酮药物作用过程,并预测了药物疗效.
普罗帕酮延长了在SQT1下的APD和仿真心电图QT间期,但是缩短了在SQT2和SQT3下的APD和仿真心电图QT间期.从系统生物学角度,通过计算使用普罗帕酮药物前后细胞间膜电压和APD空间离散度的变化,定量分析普罗帕酮降低SQT1下的T波振幅的原因.总之,对SQT1,普罗帕酮有效,对SQT2和SQT3,普罗帕酮没有改变其致心律失常的危险.仿真结果可以为普罗帕酮用于临床治疗SQTS提供理论参考.
附件SQT1~3模型及参数见网络版附录(http:// www.pibb.ac.cn).
附录
SQT1-3模型及参数[1-3]
SQT1:
N588K:
SQT2: