Structural Heterogeneity Alone Is a Sufficient Substrate for Dynamic Instability and Altered Restitution
Structural Heterogeneity Alone Is a Sufficient Substrate for Dynamic Instability and Altered Restitution
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DOI：
10.1161/circep.109.890459
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发表时间：
2010-04-01
影响因子：
8.4
通讯作者：
Smaill, Bruce H.
中科院分区：
文献类型：
--
作者：
Engelman, Zoar J.;Trew, Mark L.;Smaill, Bruce H.
背景-在结构性心脏病（SHD）中，心室APD恢复和相关电交替节律的显著变化已被证实。然而，这是否是由于结构异质性或区域变化的细胞特性仍然不确定。在这项研究中，我们解决的假设，即与SHD的结构异质性是足以改变动态恢复和增加的可能性的electricinstability.Methods和Results-Activation被模拟在一个14 × 14 mm（2）域的存在和不存在（控制）的中心区域包含不均匀的不连续性类似斑片状纤维化。在具有各向同性电导率的bidomain制剂中使用修改的LR 1心脏激活模型。双极刺激施加以上的中央区域与耦合间隔逐渐减少，从500毫秒，然后保持在105毫秒。结构的不连续性在低刺激率的电激活的影响不大，但激活时间和APD分布变得高度不均匀内和相邻的不连续区域在高利率。不一致的APD交替发生在“纤维化”和控制，但在较低的刺激率和显着更大的程度在前者。通过不连续区域的迂曲传导导致舒张间期的大幅波动，从而引起区域电不稳定性，其调节动态传导速度和APD恢复。这导致异质性传导阻滞和折返没有观察到在control. Conclusions，我们表明，结构的不连续性可以放大不协调的交替，并提供一个率依赖性基板折返。这项工作提供了新的见解纤维化可能有助于肿瘤发生的机制。(Circ心律失常电生理学2010;3：195-203.）
Background-Marked changes in ventricular APD restitution and associated alternans rhythm have been demonstrated in structural heart disease (SHD). However, whether this is due to structural heterogeneity or regional variation in cellular properties remains uncertain. In this study, we address the hypothesis that the structural heterogeneity associated with SHD is sufficient to alter dynamic restitution and increase the probability of electric instability.Methods and Results-Activation was simulated in a 14 X 14 mm(2) domain in the presence and absence (control) of a central region containing nonuniform discontinuities resembling patchy fibrosis. A modified LR1 cardiac activation model was used in a bidomain formulation with isotropic conductivities. Bipolar stimulation was imposed above the central region with coupling intervals decreasing progressively from 500 ms and then maintained at 105 ms. Structural discontinuities had little effect on electric activation at low stimulus rates, but activation time and APD distributions became highly nonuniform within and adjacent to the discontinuous region at high rates. Discordant APD alternans occurred in both "fibrosis" and control, but at lower stimulus rates and with markedly greater extent in the former. Tortuous conduction through the discontinuous region resulted in large fluctuations of diastolic intervals giving rise to regional electric instability, which modulates dynamic conduction velocity and APD restitution. This led to heterogeneous conduction block and reentry not observed in control.Conclusions-We show that structural discontinuities can amplify discordant alternans and provide a rate-dependent substrate for reentry. This work provides new insights into the mechanisms by which fibrosis may contribute to arrhythmogenesis. (Circ Arrhythm Electrophysiol. 2010;3:195-203.)