Cloherty Shaun L, Dokos Socrates, Lovell Nigel H
Graduate School of Biomedical Engineering, University of New South Wales, Sydney, Australia.
IEEE Trans Biomed Eng. 2006 Feb;53(2):164-77. doi: 10.1109/TBME.2005.862538.
In this paper, we investigate the role of sinoatrial node (SAN) cellular heterogeneity in two key aspects of normal cardiac pacemaker function: frequency entrainment of the SAN, and propagation of excitation into the atrial tissue. Using detailed ionic models of electrical activity in SAN and atrial myocytes, we have formulated a number of one-dimensional models of SAN heterogeneity based on discrete-region (in which central and peripheral SAN type cell are separated into discrete regions), gradient and mosaic models of SAN organization. Each of the different models were assessed on their ability to achieve frequency entrainment of the SAN and activation of the adjoining atrial tissue in the presence of both uniform and linearly increasing conductivity profiles. Simulation results suggest that the gradient model of SAN heterogeneity, in which cells display a smooth variation in membrane properties from the center to the periphery of the SAN, produces action potential waveshapes and a site of earliest activation consistent with experimental observations in the intact SAN. The gradient model also achieves frequency entrainment of the SAN more easily than other models of SAN heterogeneity. Based on these results, we conclude that the gradient model of SAN heterogeneity, in the presence of a uniform conductivity profile, is the most likely model of SAN organization.
在本文中，我们研究了窦房结（SAN）细胞异质性在正常心脏起搏器功能两个关键方面的作用：窦房结的频率同步，以及兴奋向心房组织的传播。利用窦房结和心房肌细胞电活动的详细离子模型，我们基于离散区域（其中中央和外周窦房结类型细胞被分隔成离散区域）、窦房结组织的梯度和镶嵌模型，构建了一些窦房结异质性的一维模型。在均匀和线性增加的电导率分布情况下，对每个不同模型实现窦房结频率同步和相邻心房组织激活的能力进行了评估。模拟结果表明，窦房结异质性的梯度模型，即细胞从窦房结中心到外周的膜特性呈现平滑变化，产生的动作电位波形和最早激活位点与完整窦房结的实验观察结果一致。与其他窦房结异质性模型相比，梯度模型也更容易实现窦房结的频率同步。基于这些结果，我们得出结论，在均匀电导率分布情况下，窦房结异质性的梯度模型是最有可能的窦房结组织模型。
