Jeong Da Un, Marcellinus Aroli, Lim Ki Moo
Department of IT Convergence Engineering, Kumoh National Institute of Technology, Gumi 39253, Korea.
Department of Medical IT Convergence Engineering, Kumoh National Institute of Technology, Gumi 39253, Korea.
Bioengineering (Basel). 2022 Nov 1;9(11):628. doi: 10.3390/bioengineering9110628.
Action potential duration (APD) alternans, an alternating phenomenon between action potentials in cardiomyocytes, causes heart arrhythmia when the heart rate is high. However, some of the APD alternans observed in clinical trials occurs under slow heart rate conditions of 100 to 120 bpm, increasing the likelihood of heart arrhythmias such as atrial fibrillation. Advanced studies have identified the occurrence of this type of APD alternans in terms of electrophysiological ion channel currents in cells. However, they only identified physiological phenomena, such as action potential due to random changes in a particular ion channel's conductivity through ion models specializing in specific ion channel currents. In this study, we performed parameter sensitivity analysis via population modeling using a validated human ventricular physiology model to check the sensitivity of APD alternans to ion channel conductances. Through population modeling, we expressed the changes in alternans onset cycle length (AOCL) and mean APD in AOCL (AO meanAPD) according to the variations in ion channel conductance. Finally, we identified the ion channel that maximally affected the occurrence of APD alternans. AOCL and AO meanAPD were sensitive to changes in the plateau Ca current. Accordingly, it was expected that APD alternans would be vulnerable to changes in intracellular calcium concentration.
动作电位时程（APD）交替现象是心肌细胞动作电位之间的一种交替现象，当心率较高时会导致心律失常。然而，在临床试验中观察到的一些APD交替现象发生在心率为100至120次/分钟的缓慢心率条件下，增加了心房颤动等心律失常的可能性。深入研究已根据细胞中的电生理离子通道电流确定了这类APD交替现象的发生情况。然而，他们只是通过专门针对特定离子通道电流的离子模型，识别了诸如由于特定离子通道电导率随机变化而产生的动作电位等生理现象。在本研究中，我们使用经过验证的人体心室生理模型通过群体建模进行参数敏感性分析，以检查APD交替现象对离子通道电导的敏感性。通过群体建模，我们根据离子通道电导的变化表达了交替起始周期长度（AOCL）和AOCL中的平均APD（AO平均APD）的变化。最后，我们确定了对APD交替现象发生影响最大的离子通道。AOCL和AO平均APD对平台期钙电流的变化敏感。因此，可以预期APD交替现象会对细胞内钙浓度的变化敏感。
