E-cigarettes and their lone constituents induce cardiac arrhythmia and conduction defects in mice

Abstract

E-cigarette use has surged, but the long-term health effects remain unknown. E-cigarette aerosols containing nicotine and acrolein, a combustion and e-cigarette byproduct, may impair cardiac electrophysiology through autonomic imbalance. Here we show in mouse electrocardiograms that acute inhalation of e-cigarette aerosols disturbs cardiac conduction, in part through parasympathetic modulation. We demonstrate that, similar to acrolein or combustible cigarette smoke, aerosols from e-cigarette solvents (vegetable glycerin and propylene glycol) induce bradycardia, bradyarrhythmias, and elevations in heart rate variability during inhalation exposure, with inverse post-exposure effects. These effects are slighter with tobacco- or menthol-flavored aerosols containing nicotine, and in female mice. Yet, menthol-flavored and PG aerosols also increase ventricular arrhythmias and augment early ventricular repolarization (J amplitude), while menthol uniquely alters atrial and atrioventricular conduction. Exposure to e-cigarette aerosols from vegetable glycerin and its byproduct, acrolein, diminish heart rate and early repolarization. The pro-arrhythmic effects of solvent aerosols on ventricular repolarization and heart rate variability depend partly on parasympathetic modulation, whereas ventricular arrhythmias positively associate with early repolarization dependent on the presence of nicotine. Our study indicates that chemical constituents of e-cigarettes could contribute to cardiac risk by provoking pro-arrhythmic changes and stimulating autonomic reflexes.

Unequal Health Risks of Integrated Volatile Organic Compounds Emitted From Various Anthropogenic Sources

“…Acrolein, as an unsaturated aldehyde, is the most reactive of the common aldehydes present in industrial manufacturing, fuel combustion and tobacco burning (Carll et al., 2022; Destaillats et al., 2002; Sithu et al., 2010). It poses a strong negative inhalation health effect due to its chronic RfC of 0.02 μg/m 3 (the lowest among VOC species), compared to 1,3‐butadiene (2 μg/m 3 ) and chloroethane (10,000 μg/m 3 ) (Faroon et al., 2008).…”

Electronic Nicotine Delivery Systems and Cardiovascular/Cardiometabolic Health

“…Mice exposed to various e-liquid constituents and aerosols (PG, VG, PG/VG, and tobacco- and menthol-flavored commercial e-liquids) showed significantly decreased HR during flavored e-cig exposures. 83 PG/VG-derived e-liquids caused the greatest changes in HR in male mice and showed no changes in female mice. Male mice also showed significantly increased HRV during flavored e-cig exposures, again with no changes observed in female mice.…”

“…These changes were then followed by increased HR and decreased HRV between exposures and postexposure in males with no observable changes in females. 83 A recent study from Nabavizadeh et al 84 suggested that no individual constituent of e-cigs or traditional cigarettes was responsible for endothelial dysfunction but that inhaled particles induce vagal nerve signaling initiated by airway irritation. These studies indicate that different components of e-cigs, including but not limited to e-liquid and nicotine, as well as biological characteristics, such as sex and metabolic comorbidities, all interact to predispose e-cig users to adverse cardiovascular outcomes.…”

Chronic Pod-Mod E-Cigarette Aerosol Exposure Induces Aortic Dysfunction in Hypercholesterolemic Mice: Role of Oxidative Stress and Inflammation

“…42 JUUL Labs, Inc.© was dominating the e-cigarette market at the time of this study and remains nowadays among the five top-selling brands. 43 Similar to cigarette smoke 31, 44 and prior generation (tank-style) e-cigarette aerosol, 24, 25, 28, 45 particulates and gases produced by pod-mod devices access the body primarily through the respiratory system yet retain the ability to modulate biological processes in other organs. 46, 47 Related to the cardiovascular system, acute inhalation of pod-mod e-cigarette aerosol increases the augmentation index (arterial stiffness), reduces the reactive hyperemia index (endothelial vasodilator function), and raises peripheral blood pressure in occasional users.…”