Auckland Bioengineering Institute and the Department of Physiology, University of Auckland, Auckland, New Zealand.
Circ Arrhythm Electrophysiol. 2010 Apr;3(2):195-203. doi: 10.1161/CIRCEP.109.890459. Epub 2010 Feb 4.
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.
Activation was simulated in a 14x14 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.
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.
在结构性心脏病（SHD）中，已经证明心室 APD 复极 restitution 发生了明显变化，并伴有交替节律。然而，这是由于结构性异质性还是细胞特性的区域变化尚不确定。在这项研究中，我们假设与 SHD 相关的结构性异质性足以改变动态复极并增加电不稳定性的可能性。
在存在和不存在（对照）包含类似于斑片状纤维化的不均匀不连续性的中央区域的情况下，在 14x14mm^2 的区域中模拟了激活。使用具有各向同性电导率的双域公式，采用改进的 LR1 心脏激活模型。在中央区域上方施加双极刺激，耦合间隔从 500ms 逐渐降低，然后保持在 105ms。在低刺激率下，结构性不连续性对电激活几乎没有影响，但在高刺激率下，在不连续区域内和周围，激活时间和 APD 分布变得高度不均匀。在“纤维化”和对照中都发生了不协调的 APD 交替，但在前者中，刺激率更低，幅度更大。不连续区域内的曲折传导导致舒张间隔的大幅波动，从而导致局部电不稳定性，从而调节动态传导速度和 APD 复极。这导致了在对照中未观察到的不均匀传导阻滞和折返。
我们表明，结构性不连续性可以放大不协调的交替，并为折返提供一个依赖于速率的底物。这项工作为纤维化如何导致心律失常发生的机制提供了新的见解。
