Conduction block in micropatterned cardiomyocyte cultures replicating the structure of ventricular cross-sections
Conduction block in micropatterned cardiomyocyte cultures replicating the structure of ventricular cross-sections
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DOI：
10.1093/cvr/cvr304
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发表时间：
2012-02-01
影响因子：
10.8
通讯作者：
Bursac, Nenad
中科院分区：
文献类型：
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作者：
Badie, Nima;Scull, James A.;Bursac, Nenad
心脏组织结构和功能的异质性与传导阻滞和心肌梗死的发生有关。然而，心脏内特定部位引发传导阻滞的倾向尚未得到系统研究。我们利用心肌细胞培养复制现实的，磁共振成像测量的组织边界和纤维方向的心室横截面的传导block.Methods和结果的发展中的作用进行调查的Sprague-Dawley新生大鼠心肌细胞micropatterned获得文化与现实的心室组织边界和随机或现实的纤维方向。在多个部位应用快速起搏，光学标测动作电位传播。刺激部位的兴奋失败或传导阻滞在远处发展，通常引发折返。在各向同性单层（0%的文化）的传导阻滞的发病率增加，包括现实的组织边界（17%），并进一步与现实的纤维方向（34%）。传导阻滞的发生率是刺激部位依赖性的，从右心室（RV）游离壁快速起搏时最高（77%）。此外，传导阻滞仅发生在右心室游离壁插入隔膜时，其中结构介导的电流源负载不匹配急剧降低波前和波后速度。纤维方向的组织边界和尖锐的梯度唯一确定的演变，形状和位置的传导阻滞lines.Conclusion我们的研究表明，特定的微观和宏观结构特征的心室确定的发病率和时空特征的传导阻滞，独立的空间异质性离子通道的表达。
Aims Structural and functional heterogeneities in cardiac tissue have been implicated in conduction block and arrhythmo-genesis. However, the propensity of specific sites within the heart to initiate conduction block has not been systematically explored. We utilized cardiomyocyte cultures replicating the realistic, magnetic resonance imaging-measured tissue boundaries and fibre directions of ventricular cross-sections to investigate their roles in the development of conduction block.Methods and results The Sprague-Dawley neonatal rat cardiomyocytes were micropatterned to obtain cultures with realistic ventricular tissue boundaries and either random or realistic fibre directions. Rapid pacing was applied at multiple sites, with action potential propagation optically mapped. Excitation either failed at the stimulus site or conduction block developed remotely, often initiating reentry. The incidence of conduction block in isotropic monolayers (0% of cultures) increased with the inclusion of realistic tissue boundaries (17%) and further with realistic fibre directions (34%). Conduction block incidence was stimulus site-dependent and highest (77%) with rapid pacing from the right ventricular (RV) free wall. Furthermore, conduction block occurred exclusively at the insertion of the RV free wall into the septum, where structure-mediated current source-load mismatches acutely reduced wavefront and waveback velocity. Tissue boundaries and sharp gradients in fibre direction uniquely determined the evolution, shape, and position of conduction block lines.Conclusion Our study suggests that specific micro-and macrostructural features of the ventricle determine the incidence and spatiotemporal characteristics of conduction block, independent of spatial heterogeneities in ion channel expression.