心衰情况下心室肌细胞透壁电生理特异性的仿真研究

Simulation Study of Transmural Cellular Electrical Properties in Failed Human Heart

仿真研究心衰情况下心室肌细胞离子通道的变异对细胞电生理和透壁特异性的影响机制,以及心力衰竭下心室透壁复极化的改变与心律失常之间的关系。基于反映正常和衰竭人体心肌细胞离子通道透壁特异性的实验数据,建立离子通道水平的心肌细胞电生理数学模型,模拟仿真研究心衰情况下心室肌心外膜、中层、心内膜细胞电生理透壁特异性的变化。结果:仿真研究发现心衰导致透壁心室肌细胞电生理重建,透壁细胞的动作电位持续时间都有明显的延长,改变了动作电位的透壁特异性,进而减小了动作电位的透壁梯度,同时衰竭心脏中快步率时动作电位的比率依赖性会增加。模型研究认为这可能与心衰细胞中离子电流ICaL和Iks的透壁特异性的电生理重构有关。所发展的细胞模型不仅可以辅助细胞电生理实验分析研究,同时也是今后仿真研究心衰情况下心肌细胞兴奋-收缩耦联力学特性的重要基础。

Simulation study of transmural cellular electrical properties in failed human heart and relationship between alterations of repolarization and arrhythmia mechanisms in heart failure. Based on experimental data of transmural electrophysiological heterogeneities in control and failing human hearts, we modeled the human ventricular cellular action potential and present simulation study of the transmural electrophysiological heterogeneities .of different ventricular cell types in heart failure. Simulation results showed that heart failure could cause transmural electrical remodeling and change the transmural heterogeneity in action potentials, and thus resulted in a reduction of transmural action potential gradients. Investigation also showed that the APD rate - dependence in heart failure increased compared with that in control heart at fast rate. The results also showed that prolonged action potential duration （APD） and APD rate-adaptation were markedly transmural heterogeneous in heart failure than those in controlled heart which might be due to enhanced transmural heterogeneities of ICaL and Ikn in myocytes. The proposed model of the failed heart cellular action potential can serve not only as a powerful tool for Cell electrophysiology experimental study but also as a paradigm for studying the failed heart＇s mechanical properties with excitation-contraction coupling.