Pacing and Ionic Conductance Effects on Excitation Waves in Early-Afterdepolarization Cardiac Models

Abnormal excitation waves of heart result in life-threatening cardiac arrhythmias, such as, ventricular fibrillation and ventricular tachycardia; these arrhythmias often originate from early afterdepolarizations (EADs) capable cardiac cells. We investigate how pacing and ionic conductances affect the generation of EADs in action potential (AP) of cardiac cell models, and explore the role of such EADs-AP in excitation wave patterns in tissue models. Our study identifies three major AP states: normal APs, APs with regular or irregular EADs, and APs with repolarization failure, which are influenced by pacing frequency and model conductance values. Furthermore, action potential duration (APD) bifurcation diagrams reveal that AP states, comprising different degrees of EADs therein, can be obtained depending on pacing frequency, consistent with experimental observations. Our two- and three-dimensional tissue simulations show the impact of pacing-dependent AP states on the instability of excitation wave patterns. In particular, an AP state with increasing oscillatory EADs, without returning to the resting membrane potential under pacing, leads to either phase wave or spiral (scroll) wave turbulence patterns, whereas a single spiral (scroll) wave pattern with a stable core is maintained by AP states returning to the resting membrane potential. We also observe wave patterns without any spiral formation, predominantly linked with cellular normal AP states, and wave propagation failure without excitation, driven by repolarization failure type AP states. Our findings provide insights into the complex interplay between pacing, ionic conductances, and EADs in cardiac arrhythmogenesis, with implications for understanding cardiac rhythm disorders.