Origin of ventricular fibrillation triggers in a model of localized repolarization heterogeneity

Heterogeneities in ventricular repolarization contribute significantly to the genesis of ventricular fibrillation (VF). Although clinical arrhythmias are spontaneously triggered by premature ventricular complexes, these triggers are difficult to document and little is known about their site of origin.

The purpose of this study was to characterize spontaneous VF initiation in an experimental model of repolarization heterogeneity and to identify the origin of triggers in relation to the spatial dispersion of repolarization.

Spatially limited repolarization heterogeneity was created in isolated perfused porcine right ventricles (N = 16) by local administration of pinacidil (20 μM) in a terminal branch of the right coronary artery. High-resolution optical mapping and pseudo-electrocardiography were performed under control conditions and after pinacidil perfusion.

No arrhythmia occurred at baseline, but 74 VF episodes were observed in 13 hearts (82%) after pinacidil perfusion and were most often initiated by a ventricular trigger with a short coupling interval (297 ± 66 ms). Sixteen VF initiations were optically mapped in 4 hearts. Mapping showed triggers originating in all cases from the border zone between altered and normal repolarization areas where local action potential duration and repolarization time gradients were steep (15.9 and 15.8 ms/mm vs 1.5 and 3.0 ms/mm at nontrigger sites). Optical action potential traces were compatible with a phase 2 reexcitation mechanism. The subsequent VF cycles were driven by activities located in the same region.

This model of localized repolarization heterogeneity is able to produce spontaneous VF initiation. Our study demonstrates that VF triggers originate consistently from the border zone of repolarization dispersion.