Abstract 20454: Electronic Cigarette Aerosols and Constituents Induce Bradycardia and Prolonged QT in Mice -- Does E-Cigarette Use Increase Cardiovascular Disease Risk?

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Introduction: Electronic nicotine delivery systems (ENDS, including E-cigarettes) use is increasing rapidly, especially among youth who perceive ENDS as generally safer than smoking. The cardiovascular disease (CVD) risk of ENDS, however, is unknown.

Objective: To investigate acute electrocardiogram (ECG) effects of inhalation exposure to ENDS aerosols relative to mainstream cigarette smoke (MCS) or to aldehydes at levels present in ENDS aerosols.

Methods: Healthy C57BL/6J male mice implanted with ECG transmitters were exposed acutely (for 9 min) to ENDS aerosol, MCS (3R4F), nicotine-free MCS (1R5F), or ENDS constituents. ECG morphology was compared with time-matched, filtered-air controls using two way repeated measures ANOVA (P<0.05).

Results: Exposure to either first-generation ENDS aerosol (bluPlus Classic Tobacco, bluCT: 16 mg/ml nicotine, n=6) or MCS (3R4F cigarette, n=6) induced a rapid-onset bradycardia (mean effect ±SE: bluCT, –-5±1%; 3R4F, -27±1%; P<0.05) that reversed to baseline at post-exposure. Because ENDS contain humectants (propylene glycol, PG; vegetable glycerin, VG), mice were exposed to aerosols of PG (100%), VG (100%) and PG:VG (50:50), and each significantly decreased heart rate (PG:VG, -39±1%, n=8; VG, -31±1% n=8; PG, -13±1%, n=8). Exposure to PG:VG or VG alone significantly prolonged QT interval (11±1% or 7±1%, respectively) and QTc (9±1% or 10±1%) after bradycardia subsided. When heated, humectants generate the aldehydes, acrolein, acetaldehyde, and formaldehyde, of which only acrolein (n=8 each), at levels present in ENDS aerosols, induced bradycardia in mice. In mice implanted with blood pressure transmitters, both acrolein and PG:VG ENDS aerosol increased blood pressure preceding onset of bradycardia.

Conclusions: Like MCS, ENDS aerosols strongly affect cardiovascular function in mice. Heated humectants generate aldehydes. Exposure to acrolein (largely a product of VG) recapitulated effects of ENDS aerosols and MCS, suggesting stimulation of a nicotine-independent pressor response leading to compensatory baroreflex-mediated bradycardia. Increased heterogeneity of ventricular repolarization with PG:VG and VG suggests that the use of ENDS may increase risks of arrhythmia and overall CVD.

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