Acute Effects of Electronic Cigarette Aerosol Inhalation on Vascular Function Detected at Quantitative MRI

Abstract

lectronic cigarettes (hereafter, e-cigarettes) deliver nicotine by the electric heating and aerosolization of a flavored solution, or e-liquid (1). E-cigarettes are a public health issue because of their widespread use, especially among teenagers, despite uncertainty about their effect on long-term health (2). Many studies now question whether e-cigarette aerosol inhalation, or vaping, is safe (3-11), and it was found to cause vascular endothelial damage (8,9) and alterations in vascular tone (10,11). The basic constituents of e-liquids, primarily propylene glycol and glycerol, can form irritant acetals even at room temperature (3) and carcinogens at typical working device temperatures (5,6). Moreover, metals in the form of fine (diameter , 2.5 mm) and ultrafine (diameter , 100 nm) particles, which are likely generated by the heating element, have been detected in ecigarette aerosol in concentrations similar to or higher than in conventional cigarettes (7). These particulates, together with trillions of free radicals (4), are implicated in nose, throat, and respiratory airway irritation, lung inflammation, and nervous system damage (7,12). Once inhaled, ultrafine particles and the oxidant species located on their surface can translocate into the vascular space (13), resulting in a state of chronic vascular inflammation and oxidative stress noxious to endothelial function. Moreover, ultrafine particles can penetrate the blood-brain barrier, potentially leading to neuroinflammation and neurotoxicity (14).We hypothesized that e-cigarette aerosol inhalation, in the absence of nicotine, exerts systemic, acute, detrimental effects on the vascular system. Therefore, we measured several quantitative MRI parameters sensitive to vascular function and tone across multiple vascular beds before and after nicotine-free e-cigarette inhalation in healthy young

JUUL and Combusted Cigarettes Comparably Impair Endothelial Function

“…3,28,29 It is likely, however, that the difference in nicotine absorption from JUUL and conventional e-cig aerosol does not directly dictate the magnitude of the vascular response, which we have already observed to be saturating in this model even by very brief (2 seconds) mainstream exposures to cigarette smoke and IQOS aerosol. 20 While we have reported a positive correlation between the concentration of nicotine in heavily diluted tobacco sidestream smoke and the extent to which FMD is impaired in rats exposed to it, 30 the fact that FMD is still impaired in humans inhaling nicotine-free e-cig aerosol 22 and in rats inhaling marijuana sidestream smoke 19 indicates that the nicotine is not the main driver of this effect.…”

“…12,15 Using this technique, we showed that FMD is also impaired in rats by brief exposures to mainstream and sidestream smoke or mainstream aerosols from cigarettes, little cigars, combustible marijuana, and IQOS "heat-not-burn" tobacco products. [17][18][19][20] Acute use of e-cigs 8/30/19 4 with or without nicotine in humans impairs several measures of endothelial function including FMD 21,22 and we have reported that nitric oxide production from cultured endothelial cells is impaired when the cells are incubated in serum from chronic e-cig use. 23 Here we report that acute mainstream exposure to aerosol from JUUL or from previous generation e-cigs using freebase nicotine impairs vascular function comparably to combusted cigarette smoke and delivers considerably more nicotine to the blood on a per puff basis.…”

“…[ Figure 4 goes here] 21 previously reported that exposure to previous generation e-cig aerosol leads to adverse effects on oxidative stress and vascular function in humans, and reports of harmful effects on hemodynamics and arterial stiffness are accumulating. 22,26,27 Our study focuses on the effect of acute exposure to JUUL on vascular function. Our results in this rat model indicate that brief use of a JUUL, a previous generation e-cig, or a Marlboro Red cigarette all led to comparable impairment of endothelial function, suggesting that the adverse effect of cigarettes on vascular endothelial function that has been a known consequence of cigarette smoking since the 1990s 12,15 is not prevented by use of JUUL.…”

Quantitative and Dynamic MRI Measures of Peripheral Vascular Function

“…By quantifying macrovascular blood flow dynamically in the feeding artery, the time to peak flow and the duration of forward flow can be measured. These parameters are increased in the presence of PAD (Langham et al, 2013a) and are sensitive to early changes in endothelial function that occur with smoking, aging (Langham et al, 2015), and have recently been shown to be acutely impaired following nicotine-free e-cigarette aerosol inhalation (Caporale et al, 2019).…”

Special issue on “Developmental effects of smoking, vaping, and cannabis use”

“…Fluids are available that have only flavorings and carrier liquid, but recent reports indicate that these can still cause serious health effects. A new study in human volunteers demonstrates that vaping e‐liquids, even those that do not contain nicotine, can have acute effects on the vascular endothelium, reducing peak blood flow velocity and luminal flow‐mediated dilation in the superficial femoral artery and vein (Caporale et al, ). If such changes were to occur in the uteroplacental circulation of pregnant women, dangerous hypoxic conditions could occur for the embryo/fetus.…”