Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708, USA.
Am J Physiol Heart Circ Physiol. 2010 Apr;298(4):H1209-18. doi: 10.1152/ajpheart.00689.2009. Epub 2010 Jan 22.
Electrical propagation in diseased and aging hearts is strongly influenced by structural changes that occur in both the intracellular and interstitial spaces of cardiac tissue; however, very few studies have investigated how interactions between the two spaces affect propagation at the microscale. In this study, we used one-dimensional microstructural computer models of interconnected ventricular myocytes to systematically investigate how increasing the effective interstitial resistivity (rho(oeff)) influences action potential propagation in fibers with variations in intracellular properties such as cell coupling and cell length. Changes in rho(oeff) were incorporated into a monodomain model using a correction to the intracellular properties that was based on bidomain simulations. The results showed that increasing rho(oeff) in poorly coupled one-dimensional fibers alters the distribution of electrical load at the microscale and causes propagation to become more continuous. In the poorly coupled fiber, this continuous state is characterized by decreased gap junction delay, sustained conduction velocity, increased sodium current, reduced maximum upstroke velocity, and increased safety factor. Long, poorly coupled cells experience greater loading effects than short cells and show the greatest initial response to changes in rho(oeff). In inhomogeneous fibers with adjacent well-coupled and poorly coupled regions, increasing rho(oeff) in the poorly coupled region also reduces source-load mismatch, which delays the onset of conduction block and reduces the dispersion of repolarization at the transition between the two regions. Increasing the rho(oeff) minimizes the effect of cell-to-cell variations and may influence the pattern of activation in critical regimes characterized by low intercellular coupling, microstructural heterogeneity, and reduced or abnormal membrane excitability.
病变和衰老心脏中的电传播强烈受到细胞内和心肌组织间隙空间中发生的结构变化的影响；然而，很少有研究调查两个空间之间的相互作用如何在微观尺度上影响传播。在这项研究中，我们使用了相互连接的心室肌细胞的一维微观结构计算机模型，系统地研究了细胞内特性（如细胞耦合和细胞长度）变化时，增加有效间质电阻率（rho(oeff)）如何影响纤维中的动作电位传播。rho(oeff)的变化通过基于双域模拟的对细胞内特性的修正被纳入单域模型中。结果表明，在耦合不良的一维纤维中增加 rho(oeff)会改变微观尺度上的电负荷分布，并导致传播变得更加连续。在耦合不良的纤维中，这种连续状态的特征是间隙连接延迟降低、传导速度持续增加、钠电流增加、最大上升速度降低和安全系数增加。长而耦合不良的细胞比短细胞经历更大的加载效应，并对 rho(oeff)的变化表现出最大的初始反应。在具有相邻良好耦合和不良耦合区域的不均匀纤维中，增加不良耦合区域中的 rho(oeff)也会减少源-负载不匹配，从而延迟传导阻滞的发生，并减少两个区域之间过渡处复极化的弥散。增加 rho(oeff)可以最小化细胞间变化的影响，并可能影响低细胞间耦合、微观结构异质性以及减少或异常膜兴奋性的临界状态下的激活模式。
