Cholinergic atrial fibrillation in a computer model of a two-dimensional sheet of canine atrial cells with realistic ionic properties
Cholinergic atrial fibrillation in a computer model of a two-dimensional sheet of canine atrial cells with realistic ionic properties
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DOI：
10.1161/01.res.0000019783.88094.ba
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发表时间：
2002-05-17
影响因子：
20.1
通讯作者：
Nattel, S
中科院分区：
文献类型：
--
作者：
Kneller, J;Zou, RQ;Nattel, S
心房颤动 (AF) 的经典概念植根于 Moe 的多小波假设和简单的细胞自动机计算机模型。最近的实验工作提出了关于多小波机制的问题，表明 AF 背后存在一个离散的“驱动区域”。我们通过具有真实离子和耦合特性的 5 X 10 厘米心房细胞片的二维计算机模型重新探索了 AF 的理论基础。迷走神经作用是根据乙酰胆碱 (ACh) 效应的膜片钳研究制定的。在控制下，单一的额外刺激会导致高度蜿蜒的不稳定螺旋波。模拟电图显示纤维性颤动活动，其主频率（DIF，6.5 Hz）与平均速率相关。均匀的 ACh 将螺旋波的核心曲折减少了大约 70%（通过螺旋波尖端位置的标准偏差测量）并将 DF 加速到 17.0 Hz。模拟的迷走神经诱导的不应期异质性导致波前破裂，因为较短不应期区域中的加速折返活动撞击了由于较长不应期而无法以 1:1 方式响应的区域。在 7 次模拟中，涵盖了提供持续 AF 的条件范围，其中 5 次是由单一主导螺旋波维持的。平均而言，存在 3.0+/-1.3 个小波（范围：1 至 7）。大多数小波都是短暂的，对 AF 维持没有贡献。与多小波假设的预测相反，但与最近的实验证据一致，我们的模型表明 AF 可以由相对稳定的初级螺旋波发生器产生，并且具有显着的组织性。我们的结果表明，迷走性房颤可能是由乙酰胆碱诱导的初级螺旋波发生器的稳定和异质组织反应的混乱引起的。本文全文可在 http://www.circresaha.org 上获取。
Classical concepts of atrial fibrillation (AF) have been rooted in Moe's multiple-wavelet hypothesis and simple cellular-automaton computer model. Recent experimental work has raised questions about the multiple-wavelet mechanism, suggesting a discrete "driver region" underlying AF. We reexplored the theoretical basis for AF with a 2-dimensional computer model of a 5 X 10-cm sheet of atrial cells with realistic ionic and coupling properties. Vagal actions were formulated based on patch-clamp studies of acetylcholine (ACh) effects. In control, a single extrastimulus resulted in a highly meandering unstable spiral wave. Simulated electrograms showed fibrillatory activity, with a dominant frequency (DIF, 6.5 Hz) that correlated with the mean rate. Uniform ACh reduced core meander of the spiral wave by approximate to70% (as measured by the standard deviation of spiral-wave tip position) and accelerated the DF to 17.0 Hz. Simulated vagally induced refractoriness heterogeneity caused wavefront breakup as accelerated reentrant activity in regions of short refractoriness impinged on regions unable to respond in a 1: 1 fashion because of longer refractoriness. In 7 simulations spanning the range of conditions giving sustained AF, 5 were maintained by single dominant spiral waves. On average, 3.0+/-1.3 wavelets were present (range, 1 to 7). Most wavelets were short-lived and did not contribute to AF maintenance. In contrast to predictions of the multiple-wavelet hypothesis, but in agreement with recent experimental evidence, our model indicates that AF can result from relatively stable primary spiral-wave generators and is significantly organized. Our results suggest that vagal AF may arise from ACh-induced stabilization of the primary spiral-wave generator and disorganization of the heterogeneous tissue response. The full text of this article is available at http://www.circresaha.org.