Sympathomimetic Effects of Acute E-Cigarette Use: Role of Nicotine and Non-Nicotine Constituents

Abstract

Background: Chronic electronic (e) cigarette users have increased resting cardiac sympathetic nerve activity and increased susceptibility to oxidative stress. The purpose of the present study is to determine the role of nicotine versus non-nicotine constituents in e-cigarette emissions in causing these pathologies in otherwise healthy humans.

Methods and results: Thirty-three healthy volunteers who were not current e-cigarette or tobacco cigarette smokers were studied. On different days, each participant used an e-cigarette with nicotine, an e-cigarette without nicotine, or a sham control. Cardiac sympathetic nerve activity was determined by heart rate variability, and susceptibility to oxidative stress was determined by plasma paraoxonase activity. Following exposure to the e-cigarette with nicotine, but not to the e-cigarette without nicotine or the sham control, there was a significant and marked shift in cardiac sympathovagal balance towards sympathetic predominance. The decrease in high-frequency component and the increases in the low-frequency component and the low-frequency to high-frequency ratio were significantly greater following exposure to the e-cigarette with nicotine compared with exposure to the e-cigarette without nicotine or to sham control. Oxidative stress, as estimated by plasma paraoxonase, did not increase following any of the 3 exposures.

Conclusions: The acute sympathomimetic effect of e-cigarettes is attributable to the inhaled nicotine, not to non-nicotine constituents in e-cigarette aerosol, recapitulating the same heart rate variability pattern associated with increased cardiac risk in multiple populations with and without known cardiac disease. Evidence of oxidative stress, as estimated by plasma paraoxonase activity, was not uncovered following acute e-cigarette exposure.

Keywords: electronic cigarettes; heart rate variability; nicotine; oxidant stress; sympathetic nervous system; tobacco.

© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Figures

Figure 1

Changes in HRV variables and heart rate in participants following acute exposures. Following exposure to e‐cigarettes with nicotine compared with e‐cigarettes without nicotine or sham control, the sympathovagal balance was significantly shifted to sympathetic predominance. Cardiac vagal tone, as estimated by the high‐frequency (HF) component (A), significantly decreased, and sympathetic tone as estimated by the low‐frequency (LF) component (B) and LF to HF ratio (C), significantly increased. Similarly, heart rate (D) significantly increased following exposure to e‐cigarettes with nicotine compared with e‐cigarettes without nicotine or sham control. bpm indicates beats per minute; EC, e‐cigarettes; HR, heart rate; nu, normalized units.

Figure 2

E‐cigarette exposure group subdivided by plasma nicotine/cotinine levels. When the group who used the e‐cigarette with nicotine was further subdivided into those with and without an increase in plasma nicotine/cotinine, the sympathovagal balance was significantly shifted to sympathetic predominance only in the group with, but not without, a detectable increase in plasma nicotine/cotinine, compared with e‐cigarettes without nicotine or sham control. Cardiac vagal tone, as estimated by the high‐frequency (HF) component (A) significantly decreased, and sympathetic tone as estimated by the low‐frequency (LF) component (B) and LF to HF ratio (C), significantly increased only in the group with—not without—detectable nicotine/cotinine compared with exposure to e‐cigarettes without nicotine or sham control. Similarly, heart rate (D) significantly increased in the group with but not without, an increase in nicotine/cotinine compared to e‐cigarettes without nicotine or sham control. bpm indicates beats per minute; EC, e‐cigarettes; HR, heart rate; nu, normalized units.