Department of Biomedical Engineering, Duke University, 3000 Science Drive, Hudson Hall Room 136, Durham, NC 27708, USA.
Cardiovasc Res. 2012 Feb 1;93(2):263-71. doi: 10.1093/cvr/cvr304. Epub 2011 Nov 9.
Structural and functional heterogeneities in cardiac tissue have been implicated in conduction block and arrhythmogenesis. 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.
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.
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.
心脏组织的结构和功能异质性与传导阻滞和心律失常的发生有关。然而，心脏内特定部位引发传导阻滞的倾向尚未得到系统探索。我们利用模拟心脏磁共振成像测量的心室横截面组织边界和纤维方向的心肌细胞培养物，研究它们在传导阻滞发展中的作用。
利用 Sprague-Dawley 新生大鼠心肌细胞微图案化技术，获得具有真实心室组织边界和随机或真实纤维方向的培养物。快速起搏应用于多个部位，通过光学映射来测量动作电位传播。刺激部位要么兴奋失败，要么远程发生传导阻滞，通常引发折返。各向同性单层（培养物的 0%）中的传导阻滞发生率随着包含真实组织边界（17%）和进一步包含真实纤维方向（34%）而增加。传导阻滞的发生率与刺激部位有关，右心室（RV）游离壁的快速起搏时发生率最高（77%）。此外，传导阻滞仅发生在 RV 游离壁插入间隔处，该处结构介导的电流源-负载不匹配会急剧降低波前和波后速度。组织边界和纤维方向的急剧梯度独特地决定了传导阻滞线的演变、形状和位置。
本研究表明，心室的特定微观和宏观结构特征决定了传导阻滞的发生率和时空特征，而与离子通道表达的空间异质性无关。
