Disruptions to cardiac tissue microstructure are common in diseased or injured myocardium and are known substrates for arrhythmias. However, we have a relatively coarse understanding of the relationships between myocardial tissue microstructure, propagation velocity and calcium cycling, due largely to the limitations of conventional experimental tools. To address this, we used microcontact printing to engineer strands of cardiac tissue with eight different widths, quantified several structural and functional parameters and established correlation coefficients. As strand width increased, actin alignment, nuclei density, sarcomere index and cell aspect ratio decreased with unique trends. The propagation velocity of calcium waves decreased and the rise time of calcium transients increased with increasing strand width. The decay time constant of calcium transients decreased and then slightly increased with increasing strand width. Based on correlation coefficients, actin alignment was the strongest predictor of propagation velocity and calcium transient rise time. Sarcomere index and cell aspect ratio were also strongly correlated with propagation velocity. Actin alignment, sarcomere index and cell aspect ratio were all weak predictors of the calcium transient decay time constant. We also measured the expression of several genes relevant to propagation and calcium cycling and found higher expression of the genes that encode for connexin 43 (Cx43) and a subunit of L-type calcium channels in thin strands compared to isotropic tissues. Together, these results suggest that thinner strands have higher values of propagation velocity and calcium transient rise time due to a combination of favorable tissue microstructure and enhanced expression of genes for Cx43 and L-type calcium channels. These data are important for defining how microstructural features regulate intercellular and intracellular calcium handling, which is needed to understand mechanisms of propagation in physiological situations and arrhythmogenesis in pathological situations.

中文翻译：

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通过心脏组织工程链中的组织微观结构调节钙动力学和传播速度。

对心脏组织微结构的破坏在患病或受伤的心肌中很常见，并且是心律不齐的已知底物。但是，由于传统实验工具的局限性，我们对心肌组织的微结构，传播速度和钙循环之间的关系有相对粗略的了解。为了解决这个问题，我们使用微接触印刷技术设计了八种不同宽度的心脏组织链，量化了一些结构和功能参数，并建立了相关系数。随着链宽度的增加，肌动蛋白排列，细胞核密度，肌小节指数和细胞长径比均以独特的趋势下降。随着链条宽度的增加，钙波的传播速度降低，钙瞬变的上升时间增加。钙瞬变的衰减时间常数随着链宽的增加先降低然后略有增加。基于相关系数，肌动蛋白比对是传播速度和钙瞬变上升时间的最强预测因子。肌节指数和细胞长宽比也与繁殖速度密切相关。肌动蛋白比对，肌小节指数和细胞长径比都是钙瞬变衰减时间常数的弱预测指标。我们还测量了与繁殖和钙循环相关的几个基因的表达，发现与各向同性组织相比，编码连接蛋白43（Cx43）和L型钙通道亚单位的基因的表达更高。一起，这些结果表明，由于有利的组织微结构和Cx43和L型钙通道基因的增强表达的结合，较细的链具有较高的传播速度和钙瞬变上升时间值。这些数据对于定义微结构特征如何调节细胞间和细胞内钙的处理非常重要，这对于理解生理情况下的传播机制和病理情况下的心律失常是必需的。