Seemann Gunnar, Höper Christine, Sachse Frank B, Dössel Olaf, Holden Arun V, Zhang Henggui
Institute of Biomedical Engineering, University Karlsruhe (TH), Kaiserstrasse 12, 76128 Karlsruhe, Germany.
Philos Trans A Math Phys Eng Sci. 2006 Jun 15;364(1843):1465-81. doi: 10.1098/rsta.2006.1781.
Investigating the mechanisms underlying the genesis and conduction of electrical excitation in the atria at physiological and pathological states is of great importance. To provide knowledge concerning the mechanisms of excitation, we constructed a biophysical detailed and anatomically accurate computer model of human atria that incorporates both structural and electrophysiological heterogeneities. The three-dimensional geometry was extracted from the visible female dataset. The sinoatrial node (SAN) and atrium, including crista terminalis (CT), pectinate muscles (PM), appendages (APG) and Bachmann's bundle (BB) were segmented in this work. Fibre orientation in CT, PM and BB was set to local longitudinal direction. Descriptions for all used cell types were based on modifications of the Courtemanche et al. model of a human atrial cell. Maximum conductances of Ito, IKr and ICa,L were modified for PM, CT, APG and atrioventricular ring to reproduce measured action potentials (AP). Pacemaker activity in the human SAN was reproduced by removing IK1, but including If, ICa,T, and gradients of channel conductances as described in previous studies for heterogeneous rabbit SAN. Anisotropic conduction was computed with a monodomain model using the finite element method. The transversal to longitudinal ratio of conductivity for PM, CT and BB was 1:9. Atrial working myocardium (AWM) was set to be isotropic. Simulation of atrial electrophysiology showed initiation of APs in the SAN centre. The excitation spread afterwards to the periphery near to the region of the CT and preferentially towards the atrioventricular region. The excitation extends over the right atrium along PM. Both CT and PM activated the right AWM. Earliest activation of the left atrium was through BB and excitation spread over to the APG. The conduction velocities were 0.6ms-1 for AWM, 1.2ms-1 for CT, 1.6ms-1 for PM and 1.1ms-1 for BB at a rate of 63bpm. The simulations revealed that bundles form dominant pathways for atrial conduction. The preferential conduction towards CT and along PM is comparable with clinical mapping. Repolarization is more homogeneous than excitation due to the heterogeneous distribution of electrophysiological properties and hence the action potential duration.
研究生理和病理状态下心房电兴奋的产生和传导机制具有重要意义。为了提供有关兴奋机制的知识，我们构建了一个生物物理详细且解剖学准确的人体心房计算机模型，该模型纳入了结构和电生理异质性。三维几何结构从可视女性数据集提取。在这项工作中，对窦房结（SAN）和心房进行了分割，包括终嵴（CT）、梳状肌（PM）、心耳（APG）和巴赫曼束（BB）。CT、PM和BB中的纤维取向设置为局部纵向方向。所有使用的细胞类型的描述均基于对Courtemanche等人的人体心房细胞模型的修改。对PM、CT、APG和房室环的Ito、IKr和ICa,L的最大电导率进行了修改，以重现测量的动作电位（AP）。通过去除IK1，但包括If、ICa,T以及通道电导率梯度，重现了人类SAN中的起搏器活动，如先前对异质性兔SAN的研究所描述。使用有限元方法通过单域模型计算各向异性传导。PM、CT和BB的横向与纵向电导率比为1:9。心房工作心肌（AWM）设置为各向同性。心房电生理模拟显示AP在SAN中心起始。随后兴奋扩散到CT区域附近的周边，并优先向房室区域扩散。兴奋沿着PM在右心房传播。CT和PM均激活右AWM。左心房最早的激活是通过BB，兴奋扩散到APG。在心率为63次/分时，AWM的传导速度为0.6m/s，CT为1.2m/s，PM为1.6m/s，BB为1.1m/s。模拟结果表明，束形成了心房传导的主要路径。向CT和沿PM的优先传导与临床标测结果相当。由于电生理特性的异质性以及因此动作电位持续时间的异质性，复极化比兴奋更均匀。
