Sodium current reduction unmasks a structure-dependent substrate for arrhythmogenesis in the normal ventricles.
Sodium current reduction unmasks a structure-dependent substrate for arrhythmogenesis in the normal ventricles.
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DOI：
10.1371/journal.pone.0086947
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Trayanova NA
中科院分区：
文献类型：
--
作者：
Boyle PM;Park CJ;Arevalo HJ;Vigmond EJ;Trayanova NA
由受损的兴奋性引起的源-汇不匹配的器官规模的致瘤后果仍然未知，阻碍了对Brugada综合征和缺血等疾病状态的病理生理学的理解。我们试图确定是否钠电流（INa）减少在结构正常的心脏揭示了区域异质性基板诱导持续心律失常室性早搏（PVC）。我们在兔心室计算机模型中进行了模拟，其中包括PVC位置（10个部位）和耦合间期（250-400 ms）、INa降低（正常水平的30或40%）和PVC后窦性心律（停止或持续）的930种独特组合。通过计算心室壁厚度和新制定的3D安全系数（SF），分别定量分析几何特征和源-库不匹配。将INa降低至其正常水平的30%，通过建立从薄组织向厚组织传播的异位波前的大面积临界源-汇失配（SF<1）区域，为持续心律失常诱导创造了基质。在相同的模拟中，但具有40%的正常INa，PVC没有诱导折返，因为SF的组织体积<1 was >小95%。同样，当PVC后窦激动持续而不是被阻止时，没有异位兴奋引起持续折返，因为窦激动突破吞没了可兴奋间隙。我们的新SF公式可以量化异位波前传播的鲁棒性在几何复杂的3D组织受损的兴奋性。这种新的方法被应用于表明，INa减少沉淀源-汇不匹配，创建一个有效的基板持续心律失常诱导的PVC起源附近的区域的心室壁扩张，如RV流出道。
Organ-scale arrhythmogenic consequences of source-sink mismatch caused by impaired excitability remain unknown, hindering the understanding of pathophysiology in disease states like Brugada syndrome and ischemia. We sought to determine whether sodium current (INa) reduction in the structurally normal heart unmasks a regionally heterogeneous substrate for the induction of sustained arrhythmia by premature ventricular contractions (PVCs). We conducted simulations in rabbit ventricular computer models with 930 unique combinations of PVC location (10 sites) and coupling interval (250–400 ms), INa reduction (30 or 40% of normal levels), and post-PVC sinus rhythm (arrested or persistent). Geometric characteristics and source-sink mismatch were quantitatively analyzed by calculating ventricular wall thickness and a newly formulated 3D safety factor (SF), respectively. Reducing INa to 30% of its normal level created a substrate for sustained arrhythmia induction by establishing large regions of critical source-sink mismatch (SF<1) for ectopic wavefronts propagating from thin to thick tissue. In the same simulations but with 40% of normal INa, PVCs did not induce reentry because the volume of tissue with SF<1 was >95% smaller. Likewise, when post-PVC sinus activations were persistent instead of arrested, no ectopic excitations initiated sustained reentry because sinus activation breakthroughs engulfed the excitable gap. Our new SF formulation can quantify ectopic wavefront propagation robustness in geometrically complex 3D tissue with impaired excitability. This novel methodology was applied to show that INa reduction precipitates source-sink mismatch, creating a potent substrate for sustained arrhythmia induction by PVCs originating near regions of ventricular wall expansion, such as the RV outflow tract.
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影响因子：
39.3
作者：
Catalano, Oronzo;Antonaci, Serena;Priori, Silvia G.
通讯作者：
Priori, Silvia G.
影响因子：
20.1
作者：
MENDEZ, C;MUELLER, WJ;URGUIAGA, X
通讯作者：
URGUIAGA, X
影响因子：
3.8
作者：
Boyle, Patrick M.;Deo, Makarand;Vigmond, Edward J.
通讯作者：
Vigmond, Edward J.
影响因子：
37.8
作者：
Lambiase, P. D.;Ahmed, A. K.;McKenna, W. J.
通讯作者：
McKenna, W. J.
影响因子：
5.5
作者：
Hoogendijk, Mark G.;Potse, Mark;Coronel, Ruben
通讯作者：
Coronel, Ruben