Supernormal Excitability Causes Alternans, Block, Wavebreak and Reentry in Cardiac Tissue

Abstract

It is well known that alternans can lead to cardiac arrhythmias. Alternans typically occurs in single cells due to voltage or calcium cycling instabilities. We showed in a previous study that alternans can also result from an instability caused by supernormal excitability (negative slope of the conduction velocity (CV) restitution curve), in the absence of voltage or calcium cycling instabilities.In this study, we used computer simulations of cables and two-dimensional domains of Luo-Rudy phase 1 model cells in which supernormal conduction was induced by decreasing the extracellular potassium concentration ([K+]o, 2.0 mmol/L) to explore arrhythmogenesis in the presence of supernormal excitability.Conduction was stable in a homogeneous cable (10 cm long) paced at one end at a basic cycle length (BCL) of 290 ms. However, when a slightly premature stimulus was applied and pacing at BCL was resumed, alternans developed gradually towards the end of the cable. This alternans was caused by supernormal CV restitution. The amplitude of alternans progressively increased until conduction block occurred at approximately 2/3 of the length of the cable.Conduction was also stable in a homogeneous two-dimensional domain (10x10 cm) paced on the left border at BCL=280 ms. However, when a premature pulse was applied at the lower half of the left border and pacing at BCL was resumed, alternans developed in the lower half of the domain via the same mechanism as in the 1D cable, while conduction in the upper half remained stable. This eventually led to conduction block and wavebreak formation in the lower half of the domain, which initiated spiral wave reentry.In conclusion, supernormal excitability represents a novel mechanism of alternans, which can lead to conduction block, wavebreak formation and reentry in cardiac tissue.