A model study of propagation of early afterdepolarizations

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. The authors 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, the authors were able to study the effects of interelement coupling resistivity and sinusoidal frequency and amplitude on the triggering of action potentials. They 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. They 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. The authors´ 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.