Garny Alan, Kohl Peter, Hunter Peter J, Boyett Mark R, Noble Denis
Department of Physiology, University of Oxford, Oxford, United Kingdom.
J Cardiovasc Electrophysiol. 2003 Oct;14(10 Suppl):S121-32. doi: 10.1046/j.1540.8167.90301.x.
Cardiac multicellular modeling has traditionally focused on ventricular electromechanics. More recently, models of the atria have started to emerge, and there is much interest in addressing sinoatrial node structure and function.
We implemented a variety of one-dimensional sinoatrial models consisting of descriptions of central, transitional, and peripheral sinoatrial node cells, as well as rabbit or human atrial cells. These one-dimensional models were implemented using CMISS on an SGI Origin 2000 supercomputer. Intercellular coupling parameters recorded in experimental studies on sinoatrial node and atrial cell-pairs under-represent the electrotonic interactions that any cardiomyocyte would have in a multidimensional setting. Unsurprisingly, cell-to-cell coupling had to be scaled-up (by a factor of 5) in order to obtain a stable leading pacemaker site in the sinoatrial node center. Further critical parameters include the gradual increase in intercellular coupling from sinoatrial node center to periphery, and the presence of electrotonic interaction with atrial cells. Interestingly, the electrotonic effect of the atrium on sinoatrial node periphery is best described as opposing depolarization, rather than necessarily hyperpolarizing, as often assumed.
Multicellular one-dimensional models of sinoatrial node and atrium can provide useful insight into the origin and spread of normal cardiac excitation. They require larger than "physiologic" intercellular conductivities in order to make up for a lack of "anatomical" spatial scaling. Multicellular models for more in-depth quantitative studies will require more realistic anatomico-physiologic properties.
心脏多细胞模型传统上一直专注于心室的电机械学。最近,心房模型开始出现,并且人们对研究窦房结的结构和功能兴趣浓厚。
我们实现了多种一维窦房结模型,这些模型包含对中央、过渡和外周窦房结细胞以及兔或人的心房细胞的描述。这些一维模型是使用CMISS在SGI Origin 2000超级计算机上实现的。在窦房结和心房细胞对的实验研究中记录的细胞间耦合参数未能充分体现任何心肌细胞在多维环境中所具有的电紧张相互作用。不出所料,为了在窦房结中心获得一个稳定的主导起搏点,细胞间耦合必须按比例放大(放大5倍)。其他关键参数包括从窦房结中心到外周细胞间耦合的逐渐增加,以及与心房细胞存在电紧张相互作用。有趣的是,心房对窦房结外周的电紧张效应最好描述为对抗去极化,而不一定是如通常所认为的超极化。
窦房结和心房的多细胞一维模型可以为正常心脏兴奋的起源和传播提供有用的见解。它们需要比“生理”细胞间电导率更大的值,以弥补“解剖学”空间缩放的不足。用于更深入定量研究的多细胞模型将需要更逼真的解剖生理特性。