Department of Physiology and Maastricht Centre of Systems Biology, Maastricht University, PO Box 616, Maastricht 6200 MD, The Netherlands.
Department of Internal Medicine, University Hospital Basel, Basel, Switzerland
Europace. 2017 Feb 1;19(2):308-318. doi: 10.1093/europace/euv445.
Loss of side-to-side electrical connections between atrial muscle bundles is thought to underlie conduction disturbances predisposing to atrial fibrillation (AF). Putatively, disruption of electrical connections occurs not only within the epicardial layer but also between the epicardial layer and the endocardial bundle network, thus impeding transmural conductions (‘breakthroughs’). However, both clinical and experimental studies have shown an enhancement of breakthroughs during later stages of AF. We tested the hypothesis that endo-epicardial uncoupling enhances endo-epicardial electrical dyssynchrony, breakthrough rate (BTR), and AF stability.
In a novel dual-layer computer model of the human atria, 100% connectivity between the two layers served as healthy control. Atrial structural remodelling was simulated by reducing the number of connections between the layers from 96 to 6 randomly chosen locations. With progressive elimination of connections, AF stability increased. Reduction in the number of connections from 96 to 24 resulted in an increase in endo-epicardial dyssynchrony from 6.6 ± 1.9 to 24.6 ± 1.3%, with a concomitant increase in BTR. A further reduction to 12 and 6 resulted in more pronounced endo-epicardial dyssynchrony of 34.4 ± 1.15 and 40.2 ± 0.52% but with BTR reduction. This biphasic relationship between endo-epicardial coupling and BTR was found independently from whether AF was maintained by re-entry or by ectopic focal discharges.
Loss of endo-epicardial coupling increases AF stability. There is a biphasic relation between endo-epicardial coupling and BTR. While at high degrees of endo-epicardial connectivity, the BTR is limited by the endo-epicardial synchronicity, at low degrees of connectivity, it is limited by the number of endo-epicardial connections.
人们认为，心房肌束之间的侧向电连接的丧失是导致心房颤动（AF）传导障碍的基础。据称，电连接的中断不仅发生在心外膜层内，而且发生在心外膜层与心内膜束网络之间，从而阻碍了跨壁传导（“突破”）。然而，临床和实验研究都表明，在 AF 的后期阶段，突破的发生率会增加。我们检验了这样一个假设，即心内膜-心外膜解耦会增强心内膜-心外膜电不同步、突破率（BTR）和 AF 的稳定性。
在一个新的人类心房双层计算机模型中，两层之间的 100%连接作为健康对照组。通过从随机选择的 96 个位置中的 6 个位置减少两层之间的连接数来模拟心房结构重塑。随着连接的逐渐消除，AF 的稳定性增加。连接数从 96 减少到 24 会导致心内膜-心外膜不同步从 6.6 ± 1.9%增加到 24.6 ± 1.3%，同时 BTR 也增加。进一步减少到 12 和 6 会导致更明显的心内膜-心外膜不同步，分别为 34.4 ± 1.15%和 40.2 ± 0.52%，但 BTR 减少。这种心内膜-心外膜耦合与 BTR 之间的双相关系独立于 AF 是通过折返还是异位灶放电维持的。
心内膜-心外膜连接的丧失会增加 AF 的稳定性。心内膜-心外膜连接与 BTR 之间存在双相关系。在高的心内膜-心外膜连接程度下，BTR 受心内膜-心外膜同步性的限制，在心内膜-心外膜连接程度较低时，BTR 受心内膜-心外膜连接数量的限制。
