The functional role of electrophysiological heterogeneity in the rabbit ventricle during rapid pacing and arrhythmias

Abstract

Electrophysiological heterogeneity in action potential recordings from healthy intact hearts remains highly variable and, where present, is almost entirely abolished at fast pacing rates. Consequently, the functional importance of intrinsic action potential duration (APD) heterogeneity in healthy ventricles, and particularly its role during rapidly activating reentrant arrhythmias, remain poorly understood. By incorporating both transmural and apicobasal APD heterogeneity within a biventricular rabbit computational model and comparing with an equivalent homogeneous model, we directly investigated the functional importance of intrinsic APD heterogeneity under fast pacing and arrhythmogenic protocols. Although differences in APD were significantly modulated at the tissue level during pacing and further reduced as pacing frequency increased, small differences were still noticeable. Such differences were further marginally accentuated/attenuated via electrotonic effects relative to wavefront propagation directions. The remaining small levels of APD heterogeneity under the fastest pacing frequencies resulted in arrhythmia initiation via heterogeneous conduction block, in contrast to complete block in the homogeneous model. Such induction mechanisms were more evident during premature stimuli at slower paced rhythms where intrinsic heterogeneity remained to a greater degree. During sustained arrhythmias, however, intrinsic heterogeneity made little difference to overall reentrant behavior, either visually, or in terms of duration, metrics quantifying filament/phase singularity dynamics, and global electrocardiogram characteristics. These findings suggest that, despite being important during arrhythmia initiation, intrinsic electrophysiological heterogeneity plays little functional role during rapid pacing and sustained arrhythmia dynamics in the healthy ventricle and thus questions the need to incorporate such detail in computational models when simulating rapid arrhythmias.