Abstract

Background: E-cigarette (e-cig) use has rapidly increased, especially among youth. Vaping has been linked to adverse cardiopulmonary effects, but the full extent of effects remains unknown. Several constituents in e-cigs may increase cardiac risk partly by disturbing cardiac electrophysiology and the autonomic nervous system. Hypothesis: E-cig aerosols will differentially induce pro-arrhythmic changes in cardiac conduction and autonomic balance in mice depending on the presence of nicotine and flavors. Methods: Electrocardiograms (ECGs) were collected by telemetry in 5 healthy male mice (C57BL/6) exposed for 6 hours to clean air or e-cig aerosols (9-minute puff sessions every 18 minutes) from JUUL e-liquids (Va. Tobacco, Mango, or Menthol at ≈5% nicotine benzoate), or a nicotine-free mixture of propylene glycol and vegetable glycerin solvents (PG:VG, 30:70 ratio). ECG morphology, heart rate variability (HRV), and arrhythmias were analyzed by mixed models with P < 0.05 (vs. Air) for all effects. Results: PG:VG increased high grade supraventricular block arrhythmias (121±45 events/hour) relative to Air (0±0 events/hour) and decreased heart rate (HR, -25±8 beats/min), whereas aerosols from all nicotine-containing e-liquids increased HR and decreased HRV, suggesting sympatho-excitation. However, these effects were significantly attenuated for Mango relative to Menthol and Va. Tobacco. As well, only PG:VG and Mango increased ventricular premature beats (VPBs, 9.6±3.7 and 5.5±1.2 events/hour, ±SEM) relative to Air (1.1±0.24 events/hour). VPBs correlated with changes in standard deviation of RR and mean HR from pre-exposure (Spearman’s r : 0.51 and -0.27, P < 0.0001). Prolonged repolarization (QTc) correlated with VPBs during exposures to PG:VG ( r = 0.38, P = 0.046), but not nicotine-containing e-liquids ( r = 0.15, P = 0.38). Conclusions: E-cigs may increase risk for cardiac arrhythmia through e-liquid solvents, which when thermally aerosolized generate toxic aldehydes and particulates. Nicotine and flavor chemicals may modify the cardiac and autonomic impacts of e-cigs. Further studies are needed to determine how e-cig aerosols induce cardiac arrhythmia and whether these effects translate to cardiac morbidity and mortality in humans.

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