Biological Physics Group, School of Physics and Astronomy, University of Manchester, Manchester M13 9PL, United Kingdom.
Eur J Pharm Sci. 2012 Jul 16;46(4):209-21. doi: 10.1016/j.ejps.2011.08.014. Epub 2011 Aug 24.
Computational models of human atrial cells, tissues and atria have been developed. Cell models, for atrial wall, crista terminalis, appendage, Bachmann's bundle and pectinate myocytes are characterised by action potentials, ionic currents and action potential duration (APD) restitution. The principal effect of the ion channel remodelling of persistent atrial fibrillation (AF), and a mutation producing familial AF, was APD shortening at all rates. Electrical alternans was abolished by the modelled action of Dronedarone. AF induced gap junctional remodelling slows propagation velocity at all rates. Re-entrant spiral waves in 2-D models are characterised by their frequency, wavelength, meander and stability. For homogenous models of normal tissue, spiral waves self-terminate, due to meander to inexcitable boundaries, and by dissipation of excitation. AF electrical remodelling in these homogenous models led to persistence of spiral waves, and AF fibrotic remodelling to their breakdown into fibrillatory activity. An anatomical model of the atria was partially validated by the activation times of normal sinus rhythm. The use of tissue geometry from clinical MRI, and tissue anisotropy from ex vivo diffusion tensor magnetic resonance imaging is outlined. In the homogenous model of normal atria, a single scroll breaks down onto spatio-temporal irregularity (electrical fibrillation) that is self-terminating; while in the AF remodelled atria the fibrillatory activity is persistent. The persistence of electrical AF can be dissected in the model in terms of ion channel and intercellular coupling processes, that can be modified pharmacologically; the effects of anatomy, that can be modified by ablation; and the permanent effects of fibrosis, that need to be prevented.
已经开发出了人类心房细胞、组织和心房的计算模型。心房壁、终嵴、心耳、Bachmann 束和梳状肌的细胞模型的特征是动作电位、离子电流和动作电位时程（APD）恢复。持续性心房颤动（AF）的离子通道重构和导致家族性 AF 的突变的主要影响是所有频率下的 APD 缩短。多非利特的模拟作用消除了电交替。AF 诱导的缝隙连接重构以所有频率降低传播速度。二维模型中的折返螺旋波的特征是其频率、波长、曲折和稳定性。对于正常组织的均匀模型，螺旋波由于曲折到无兴奋边界和兴奋耗散而自行终止。在这些均匀模型中，AF 电重构导致螺旋波持续存在，而 AF 纤维性重构导致其分解为纤维性活动。心房的解剖模型部分通过正常窦性节律的激活时间得到验证。概述了使用来自临床 MRI 的组织几何形状和来自离体扩散张量磁共振成像的组织各向异性。在正常心房的均匀模型中，单个涡旋分解成时空不规则性（电纤维性颤动），该不规则性会自行终止；而在 AF 重构的心房中，纤维性活动是持续的。可以根据离子通道和细胞间耦联过程在模型中剖析电 AF 的持续性，这些过程可以通过药理学进行修改；可以通过消融来修改解剖结构的影响；以及可以预防纤维化的永久性影响。
