Structural heterogeneity modulates effective refractory period: a mechanism of focal arrhythmia initiation.
Structural heterogeneity modulates effective refractory period: a mechanism of focal arrhythmia initiation.
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结构异质性调节有效的难治期：局灶性心律不齐的机制。
DOI：
10.1371/journal.pone.0109754
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Plank G
中科院分区：
文献类型：
--
作者：
Bishop MJ;Connolly A;Plank G
结构和电生理异质性区域周围的电紧张负荷减少可能有助于捕获局灶性触发活动，引发折返性心律失常。然而，电紧张负荷、不应性和局灶性异位的捕获如何取决于生理结构解剖的复杂性质以及病理组织重塑，尚不清楚。在这项研究中，我们进行了计算bidomain模拟与解剖详细的模型，代表兔左心室。我们使用这些模型来量化局部结构解剖和空间异质性的动作电位（AP）特性，电紧张电流和有效不应期（ERP）起搏和恢复协议之间的关系。除了组织表面之外，血管腔周围区域的下游电紧张电流峰值明显低于耦合良好的心肌（vs A/cm 2），最大AP上行速度更快（vs mV/ms），尽管APD（vs ms）和AP恢复特性明显非常相似。尽管APD相似，但与邻近耦合良好的组织相比，表面附近低电紧张负荷区域、壁内血管腔和内膜结构的ERP短至ms，导致ERP梯度急剧区域。因此，在相邻区域之间的ERP异质性窗口内定时的局灶性额外刺激容易诱导单向阻滞，诱导折返。最有效的诱导部位是大血管和心外膜之间的低ERP通道内。由于精细尺度生理结构异质性导致的电紧张负荷减少所驱动的ERP的显著差异提供了捕获局灶性活动和折返诱导的重要机制。应用于病理性心室，特别是心肌梗死，将在抗心律失常治疗中具有重要意义。
Reductions in electrotonic loading around regions of structural and electrophysiological heterogeneity may facilitate capture of focal triggered activity, initiating reentrant arrhythmias. How electrotonic loading, refractoriness and capture of focal ectopics depend upon the intricate nature of physiological structural anatomy, as well as pathological tissue remodelling, however, is not well understood. In this study, we performed computational bidomain simulations with anatomically-detailed models representing the rabbit left ventricle. We used these models to quantify the relationship between local structural anatomy and spatial heterogeneity in action potential (AP) characteristics, electrotonic currents and effective refractory periods (ERPs) under pacing and restitution protocols. Regions surrounding vessel cavities, in addition to tissue surfaces, had significantly lower peak downstream electrotonic currents than well coupled myocardium ( vs A/cm2), with faster maximum AP upstroke velocities ( vs mV/ms), although noticeably very similar APDs ( vs ms) and AP restitution properties. Despite similarities in APDs, ERPs in regions of low electrotonic load in the vicinity of surfaces, intramural vessel cavities and endocardial structures were up to ms shorter compared to neighbouring well-coupled tissue, leading to regions of sharp ERP gradients. Consequently, focal extra-stimuli timed within this window of ERP heterogeneity between neighbouring regions readily induced uni-directional block, inducing reentry. Most effective induction sites were within channels of low ERPs between large vessels and epicardium. Significant differences in ERP driven by reductions in electrotonic loading due to fine-scale physiological structural heterogeneity provides an important mechanism of capture of focal activity and reentry induction. Application to pathological ventricles, particularly myocardial infarction, will have important implications in anti-arrhythmia therapy.
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影响因子：
1.3
作者：
Vigmond, EJ;Hughes, M;Leon, LJ
通讯作者：
Leon, LJ
DOI：
10.1016/j.pbiomolbio.2007.07.012
发表时间：
2008-01
影响因子：
3.8
作者：
Vigmond EJ;Weber dos Santos R;Prassl AJ;Deo M;Plank G
通讯作者：
Plank G
DOI：
10.1109/tbme.2010.2051227
发表时间：
2010-10
期刊：
IEEE transactions on bio-medical engineering
影响因子：
--
作者：
Bishop MJ;Boyle PM;Plank G;Welsh DG;Vigmond EJ
通讯作者：
Vigmond EJ
影响因子：
4.3
作者：
Colli-Franzone, P.;Pavarino, L. F.;Taccardi, B.
通讯作者：
Taccardi, B.
影响因子：
4.6
作者：
SPACH, MS;KOOTSEY, JM
通讯作者：
KOOTSEY, JM