Remodeling in cells from different regions of the reentrant circuit during ventricular tachycardia
Remodeling in cells from different regions of the reentrant circuit during ventricular tachycardia
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DOI：
10.1161/circulationaha.105.534784
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发表时间：
2005-10-18
期刊：
影响因子：
37.8
通讯作者：
Boyden, PA
中科院分区：
文献类型：
--
作者：
Baba, S;Dun, W;Boyden, PA
背景-各向异性折返性兴奋发生在5天梗塞犬心脏的心外膜边缘区（EBZ）的重塑基质中。折返是稳定的，因为块的功能线的形成。我们假设EBZ细胞中离子电流的区域差异形成这些阻断线。因此，我们首先绘制了持续性心动过速的折返回路，然后分散细胞，从回路的中央共同通路（IZc）以及从阻断线的另一侧（IZc）的细胞（梗塞区细胞，IZs）中，方法和结果--我们在持续性室性心动过速期间绘制了梗死心脏EBZ中的折返回路（> 30秒，n = 17次发作，周期长度= 218 +/- 7.9 ms）。I-Na密度降低在两个IZc和IZO，和动力学性能的IZc INa显着改变与IZO。钠通道蛋白Na（v）1.5的结构重塑发生在IZS中，细胞表面定位不同于正常细胞。IZc和IZo具有相似但降低的I-CaL，而IZc显示Ca 2+电流动力学的变化，电流衰减加速。2D EBZ的计算机模拟表明，仅将IZC和IZO中的INa之间的差异纳入会阻止再入电路的稳定性。仅考虑IZC和IZO电池中I-CaL之间的差异也会妨碍电路的稳定性。然而，将I-Na和I-CaL电流的差异稳定的模拟折返电路，和线的块之间形成的2个不同regions.Conclusions -尽管在I-Na和I-CaL属性的差异在细胞的中心和外部通路的折返电路，由此产生的变化，在有效的不应期往往稳定折返在这个重塑基板。
Background - Anisotropic reentrant excitation occurs in the remodeled substrate of the epicardial border zone (EBZ) of the 5-day infarcted canine heart. Reentry is stabilized because of the formation of functional lines of block. We hypothesized that regional differences of ionic currents in cells of the EBZ form these lines of block. Therefore, we first mapped reentrant circuits of sustained tachycardias, then dispersed cells ( infarct zone cells, IZs) from the central common pathway of the circuit (IZc) as well as from the other side of the line of block ( outer pathway, IZo) for study.Methods and Results - We mapped reentrant circuits in the EBZ of infarcted hearts during sustained ventricular tachycardias (> 30 seconds, n = 17 episodes, cycle lengths = 218 +/- 7.9 ms). I-Na density was reduced in both IZc and IZo, and the kinetic properties of IZc INa were markedly altered versus IZo. Structural remodeling of the sodium channel protein Na(v)1.5 occurred in IZs, with cell surface localization differing from normal cells. Both IZc and IZo have similar but reduced I-CaL, whereas IZc showed changes in Ca2+ current kinetics with an acceleration of current decay. Computer simulations of the 2D EBZ showed that incorporating only differences between INa in IZc and IZo prevented stability of the reentrant circuit. Incorporating only differences between I-CaL in the IZc and IZo cells also prevented stability of the circuit. However, incorporating both I-Na and I-CaL current differences stabilized the simulated reentrant circuit, and lines of block formed between the 2 distinct regions.Conclusions - Despite differences in I-Na and I-CaL properties in cells of the center and outer pathways of a reentrant circuit, the resulting changes in effective refractory periods tend to stabilize reentry in this remodeled substrate.