Acute Oestradiol Slows Conduction in Male, but not Female, Murine Left Atria

Abstract

Pericardial adipose accumulation increases atrial fibrillation risk; however, the underlying mechanisms are not well understood. We have demonstrated that pericardial adipose expresses aromatase, indicating capacity to locally synthesise oestrogens. In Langendorff-perfused mouse hearts, atrial arrhythmia incidence correlated with the total aromatase capacity of this adipose depot, and exogenous oestradiol increased arrhythmia vulnerability. The aim of this study was to determine how acute administration of oestrogens modulate cardiac electrophysiology in male and female cardiomyocyte monolayers and intact left atria. Microelectrode array (MEA)-seeded neonatal rat ventricular myocytes (NRVMs) were exposed to increasing concentrations of oestradiol (0–100 nM) and synchronous field potentials recorded. Optical action potentials were measured from isolated adult mouse left atria stained with Di-4-ANEPPS, electrically paced and superfused with increasing concentrations of oestradiol (n = 4–10). NRVM conduction velocity (CV) and field potential duration were unaffected by acute oestradiol. Acute oestradiol prolonged action potential duration at 70% repolarisation (APD70) in both male (ΔAPD70, 100 nM oestradiol vs vehicle: 5.8 ± 0.9 ms vs 1.6 ± 1.6 ms; P = 0.037) and female atria (7.6 ± 1.0 ms vs 3.9 ± 0.9 ms; P = 0.045). A lower oestradiol concentration slowed CV in male (ΔCV, 1 nM oestradiol vs vehicle: −9.2 ± 1.8 cm s−1 vs −1.1 ± 2.7 cm s−1; P = 0.007), but not female atria (ΔCV: −2.4 ± 2.0 cm s−1 vs 0.05 ± 3.2 cm s−1; P = 0.79). Slowed action potential propagation and prolonged repolarisation are two key mechanisms underlying reentrant and triggered arrhythmias, respectively. These rapid responses to acute oestrogen administration indicate non-genomic influences on cardiomyocyte electrophysiology and may be mediated by stimulation of oestrogen receptor signalling pathways.