Acute Oestradiol Increases the Propensity for Atrial Arrhythmias in the Isolated Mouse Heart

Abstract

Atrial fibrillation (AF) is the most common sustained arrhythmia, significantly contributing to cardiovascular morbidity/mortality. Epidemiological studies have reported sex differences in AF incidence and outcomes. The influence of sex steroids on AF vulnerability is poorly understood, though clinical trial findings (ie WHI) have indicated that hormone supplementation using oestrogen-only therapy significantly increased AF risk. Experimental data addressing oestrogenic influence on atrial arrhythmias are lacking. We have previously shown that oestrogen influences ventricular electromechanical properties and arrhythmia vulnerability. The aim of this study was to assess the influence of acute oestradiol treatment on atrial arrhythmias in isolated mouse hearts. Bipolar electrograms were recorded from hearts subjected to programmed pulse stimulations in the presence/absence of 10 nM estradiol (vs vehicle control). Oestradiol significantly increased the incidence of atrial arrhythmias (# episodes; 2.8 ± 0.5 vs 0.9 ± 0.3), with the mean duration of each arrhythmic episode exhibiting similar trend. The total duration of atrial arrhythmias throughout the pulse stimulation protocol was significantly increased in the presence of oestradiol (s; 6.9 ± 3.2 vs 1.0 ± 0.4). Augmented atrial arrhythmia vulnerability was likely not due to oestrogenic action on sinus node automaticity, as no effect was observed on sinus node recovery time (ms; 424 ± 46 vs 397 ± 47). These data show for the first time in an experimental setting that acute oestrogen exposure increases cardiac vulnerability to atrial arrhythmia. This finding demonstrates potential cardiac vulnerability to local increase in oestrogen of endogenous and exogenous origin. Further studies are required to identify and target the cellular mechanisms by which oestrogen exerts this arrhythmogenic influence.