Effects of chronic exposure to usual and high doses of Bisphenol A on cardiac arrhythmias, electrophysiology, and autonomic modulation

Abstract

Background Bisphenol A (BPA) is a synthetic compound found in plastic bottles, sports equipment, or water pipes. The continuous and inevitable human exposure to BPA has been related to increased cardiovascular risk. In experimental studies, acute exposure to high BPA doses was associated with ventricular arrhythmias. However, the effects of chronic exposure to usual BPA doses (i.e., relevant for usual human exposure) on cardiac arrhythmogenicity have not been properly assessed. Purpose We aimed to assess the effects of chronic exposure to high and usual BPA doses on cardiac arrhythmias, electrophysiology, and autonomic modulation in rats. Methods Adult female Wistar rats were randomized into 3 groups: Control, BPA, and BPA-HD (n=7 each). BPA and BPA-HD rats received 50 μg/kg/day and 25 mg/kg/day of BPA, respectively, for 9 weeks. Rats were implanted with radiotelemetry ECG devices and 24-h ECG recordings were performed prior to and after application of transesophageal atrial burst pacing (4,000 stimuli/min for 20 s; 15 cycles). Heart rate variability (HRV) parameters and atrial and ventricular arrhythmias (i.e., atrial premature beats [APB], atrial fibrillation [AF], ventricular premature beats [VPB], ventricular tachycardia/fibrillation [VT/VF]) were assessed based on the 24-h ECG recordings. The left atrium was then collected and atrial depolarization velocity and action potential duration to 90% (APD90) and 50% (APD50) of complete repolarization were measured. Results Mean heart rate (p=0.48), the number of VPB (p=0.90), AF inducibility (p=0.68), and atrial action potential parameters (all p>0.05) were all similar between the 3 groups. None of the animals presented VT/VF. There was no significant difference in the number of atrial or ventricular arrhythmic events nor in the HRV parameters between BPA and Control (all p>0.05). However, BPA-HD presented a significantly higher number of APB both prior to (p=0.02) and after (p=0.04) atrial pacing, and a significantly higher number of post-pacing spontaneous AF episodes (p<0.01) compared to Control. The parasympathetic indexes SDNN, RMSSD, pNN5, and the NHF of the HRV spectrum were all significantly higher (all p<0.05), whereas the LF/HF ratio, an index of sympathetic and parasympathetic interactions, was significantly lower (p=0.01) in the BPA-HD compared with the Control rats. Conclusions In rats, chronic exposure to BPA doses relevant for usual human exposure was not associated in any significant change in cardiac arrhythmogenicity, electrophysiology, or autonomic modulation. However, high-dose BPA exposure, such as that occurring in workers in the plastics industry, led to significant increase in atrial arrhythmogenicity, including AF, that did not seem to be related to atrial electrophysiology changes. Instead, given the strong atrial proarrhythmic effects of vagal hyperactivity, this effect could be linked to the significant increase in vagal modulation induced by high-dose BPA exposure. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by a grant of the Romanian Ministry of Education and Research, CNCS – UEFISCDI