BPS2026 – Sex- and region-dependent electrophysiology and arrhythmia vulnerability in rabbit atria

Atrial fibrillation (AF) is the most common cardiac arrhythmia and is characterized by rapid and irregular atrial electrical activity resulting from adverse electrophysiological and structural remodeling. Sex differences are well-documented in AF; however, the underlying mechanisms remain unclear. This knowledge gap is partly due to limited understanding of how healthy atrial electrophysiology differs between sexes. The aim of this study was to investigate sex differences in electrophysiology and arrhythmia susceptibility in the intact rabbit atria. Hearts from young male and female New Zealand White rabbits were isolated and the atria optically mapped using voltage (RH237) and Ca 2+ -sensitive (Rhod-2 AM) indicators. Pacing was performed from the right atrium. Electrophysiology and arrhythmia susceptibility were assessed via rapid pacing and premature stimuli, with and without the parasympathomimetic carbachol (0.5 μM). Gene expression differences were evaluated with qPCR. At baseline, females exhibited similar action potential duration (APD) to males, but longer Ca 2+ transient durations and greater APD heterogeneity across the atria. This increased heterogeneity was primarily due to prolonged APD in the right atrium and interatrial region and was rate-dependent—diminishing at faster pacing frequencies. Following carbachol, APD shortened in both atria in males, but only in the right atrium in females. This more pronounced carbachol-mediated APD shortening in males was associated with increased susceptibility to pacing-induced reentrant arrhythmias. qPCR revealed sex- and chamber-specific differences in expression of genes encoding the L-type Ca 2+ channel, ryanodine receptor, muscarinic receptor, and acetylcholine-sensitive K + channel. These findings demonstrate sex and regional differences in atrial electrophysiology. Despite increased APD heterogeneity in females, the prolonged right atrial APD and diminished heterogeneity at fast rates likely prevented pacing-induced arrhythmia. Future studies will investigate the mechanisms underlying these effects and how they evolve with age to influence susceptibility to AF.