New Insights From MRI and Cell Biology Into the Acute Vascular-Metabolic Implications of Electronic Cigarette Vaping

Abstract

The popularity of electronic cigarettes (e-cigs) has grown at a startling rate since their introduction to the United States market in 2007, with sales expected to outpace tobacco products within a decade. Spurring this trend has been the notion that e-cigs are a safer alternative to tobacco-based cigarettes. However, the long-term health impacts of e-cigs are not yet known. Quantitative magnetic resonance imaging (MRI) approaches, developed in the authors' laboratory, provide conclusive evidence of acute deleterious effects of e-cig aerosol inhalation in the absence of nicotine in tobacco-naïve subjects. Among the pathophysiologic effects observed are transient impairment of endothelial function, vascular reactivity, and oxygen metabolism. The culprits of this response are currently not fully understood but are likely due to an immune reaction caused by the aerosol containing thermal breakdown products of the e-liquid, including radicals and organic aldehydes, with particle concentrations similar to those emitted by conventional cigarettes. The acute effects observed following a single vaping episode persist for 1-3 h before subsiding to baseline and are paralleled by build-up of biological markers. Sparse data exist on long-term effects of vaping, and it is likely that repeated regular exposure to e-cig aerosol during vaping will lead to chronic conditions since there would be no return to baseline conditions as in the case of an isolated vaping episode. This brief review aims to highlight the potential of pairing MRI, with its extraordinary sensitivity to structure, physiology and metabolism at the holistic level, with biologic investigations targeting serum and cellular markers of inflammation and oxidative stress. Such a multi-modal framework should allow interpretation of the impact of e-cigarette vaping on vascular health at the organ level in the context of the underlying biological alterations. Applications of this approach to the study of other lifestyle-initiated pathologies including hypertension, hypercholesterolemia, and metabolic syndrome are indicated.

Keywords: E-cigarette; MRI; endothelium; vaping; vascular.

Copyright © 2020 Wehrli, Caporale, Langham and Chatterjee.

Figures

FIGURE 1

Cascade of events following e-cigarette inhalation, initiating vascular inflammation and dysfunction. Ultra-fine particles (UFP) and free radicals, deposited on the respiratory tract are taken up by endothelial cells. This process drives endothelial activation that triggers inflammation signaling, eventually leading to vascular dysfunction (original figure).

FIGURE 2

Multi-vascular MRI protocol. The 50-min MRI protocol included a measure of peripheral vascular reactivity (PVR) to cuff-induced ischemia, followed by cerebrovascular reactivity (CVR) and aortic pulse wave velocity (PWV) quantification. PVR was assessed in the femoral vessels via multiple techniques. To stimulate reactive hyperemia the cuff was placed around the upper thigh and inflated for 5 min. CVR to hypercapnia in the form of volitional apnea was measured in the superior sagittal sinus (artwork modified from Caporale et al., 2019; Supplementary Figure B1, with permission from RSNA publisher).

FIGURE 3

Arterial velocimetry at baseline and hyperemia. (A) Blood flow velocity in the superficial femoral artery, during baseline and post-cuff occlusion (reactive hyperemia). Systolic, retrograde, and baseline velocities are indicated (Vs, Vr, and Vb, respectively). Post-ischemia, hyperemia is evaluated in terms of hyperemic index (HI) as the slope of the initial part of the velocity-time curve, peak average velocity (VP), and duration of hyperemia, referred to as time of forward flow (TFF). (B) Axial MR image of the thigh perpendicular to the femoral artery. (C) Pre- vs. post-electronic cigarette (e-cig) vaping differences for two parameters, in non-smokers, after a single episode of non-nicotinized e-cig vaping. The same MRI protocol was executed before and after e-cig use (modified from Caporale et al., 2019; Figures 2, 5, with permission from RSNA publisher).

FIGURE 4

Venous oximetry and flow-mediated dilation. (A) Post-cuff release venous oxygen saturation (SvO2) interleaved with vessel wall imaging to derive femoral artery flow-mediated dilation (FMD) measurement at 60, 90, and 120 s following cuff deflation, with respect to the lumen at rest (B). (B–D) Pre vs. post-e-cig vaping differences for the extracted metrics: (B,D) luminal FMD (FMDL), (C) pre-cuff occlusion baseline SvO2 [SvO2(b)], washout time (TW), and overshoot (A,B are original, produced from data already published in Caporale et al., 2019; (C,D) are modified from Caporale et al., 2019; Figure 5, with permission from RSNA publisher).