Wagner M B, Gibb W J, Lesh M D
Department of Medicine, University of California, San Francisco, USA.
IEEE Trans Biomed Eng. 1995 Oct;42(10):991-8. doi: 10.1109/10.464373.
Early afterdepolarizations (EAD's) are irregularities of the cardiac action potential that interrupt or retard repolarization. EAD's have been linked to the development of specific types of cardiac arrhythmias, however, the mechanism underlying the development of these arrhythmias remains unclear. We implemented a two-element kinetic model of the ventricular action potential to investigate a potentially arrhythmogenic form of triggered activity. By approximating EAD's by a sinusoidal driving force, we were able to study the effects of interelement coupling resistivity and sinusoidal frequency and amplitude on the triggering of action potentials. We demonstrated EAD's in a ventricular action potential model by altering the potassium and calcium channels to simulate experimental conditions under which EAD's occur. We also found that triggered activity depends critically on the frequency and amplitude of the driving force and also on the degree of cellular uncoupling between the elements. Our results suggest that triggered activity (due to EAD's) may be suppressed by drugs that improve coupling in unhealthy tissue, or ones that prevent EAD formation by inhibiting calcium channels.
早期后除极（EADs）是心脏动作电位的异常，会中断或延缓复极化。EADs与特定类型心律失常的发生有关，然而，这些心律失常发生的潜在机制仍不清楚。我们实施了一个心室动作电位的双元件动力学模型，以研究一种潜在的致心律失常形式的触发活动。通过用正弦驱动力近似EADs，我们能够研究元件间耦合电阻以及正弦频率和幅度对动作电位触发的影响。我们通过改变钾通道和钙通道来模拟EADs发生的实验条件，从而在心室动作电位模型中证明了EADs的存在。我们还发现，触发活动关键取决于驱动力的频率和幅度，以及元件间细胞解耦的程度。我们的结果表明，（由EADs引起的）触发活动可能会被改善不健康组织中耦合的药物或通过抑制钙通道来防止EAD形成的药物所抑制。
