Chronic exposure to electronic cigarettes results in impaired cardiovascular function in mice

Abstract

Proponents for electronic cigarettes (E-cigs) claim that they are a safe alternative to tobacco-based cigarettes; however, little is known about the long-term effects of exposure to E-cig vapor on vascular function. The purpose of this study was to determine the cardiovascular consequences of chronic E-cig exposure. Female mice (C57BL/6 background strain) were randomly assigned to chronic daily exposure to E-cig vapor, standard (3R4F reference) cigarette smoke, or filtered air ( n = 15/group). Respective whole body exposures consisted of four 1-h-exposure time blocks, separated by 30-min intervals of fresh air breaks, resulting in intermittent daily exposure for a total of 4 h/day, 5 days/wk for 8 mo. Noninvasive ultrasonography was used to assess cardiac function and aortic arterial stiffness (AS), measured as pulse wave velocity, at three times points (before, during, and after chronic exposure). Upon completion of the 8-mo exposure, ex vivo wire tension myography and force transduction were used to measure changes in thoracic aortic tension in response to vasoactive-inducing compounds. AS increased 2.5- and 2.8-fold in E-cig- and 3R4F-exposed mice, respectively, compared with air-exposed control mice ( P < 0.05). The maximal aortic relaxation to methacholine was 24% and 33% lower in E-cig- and 3R4F-exposed mice, respectively, than in controls ( P < 0.05). No differences were noted in sodium nitroprusside dilation between the groups. 3R4F exposure altered cardiac function by reducing fractional shortening and ejection fraction after 8 mo ( P < 0.05). A similar, although not statistically significant, tendency was also observed with E-cig exposure ( P < 0.10). Histological and respiratory function data support emphysema-associated changes in 3R4F-exposed, but not E-cig-exposed, mice. Chronic exposure to E-cig vapor accelerates AS, significantly impairs aortic endothelial function, and may lead to impaired cardiac function. The clinical implication from this study is that chronic use of E-cigs, even at relatively low exposure levels, induces cardiovascular dysfunction. NEW & NOTEWORTHY Electronic cigarettes (E-cigs) are marketed as safe, but there has been insufficient long-term exposure to humans to justify these claims. This is the first study to report the long-term in vivo vascular consequences of 8 mo of exposure to E-cig vapor in mice (equivalent to ~25 yr of exposure in humans). We report that E-cig exposure increases arterial stiffness and impairs normal vascular reactivity responses, similar to other risk factors, including cigarette smoking, which contribute to the development of cardiovascular disease.

Short‐Term E‐Cigarette Exposure Increases the Risk of Thrombogenesis and Enhances Platelet Function in Mice

“…Further support for the validity and the clinical applicability of our animal model derives from literature documenting that mouse studies do “map” very well to humans in the context of tobacco exposure 14, 75, 76. In fact, given the challenges in human studies and the difficulty in drawing conclusions due to the variability in the device and e‐liquid products, users’ experience, and concomitant exposure to other forms of tobacco, the current model gives us great flexibility in mimicking many aspects of human exposure.…”

“…Furthermore, a case of acute myocardial infarction in a young man was recently reported after only 1 month of e‐cigarette use 90. Separate studies showed that e‐cigarettes also induce myocardial DNA damage,91 arterial stiffness14 and stroke92 in mice. While the current data indicate that short‐term exposure to e‐cigarettes is associated with cardiovascular harm, one can speculate that longer use/exposure to e‐cigarette would have even more detrimental effects; this will be the scope of future investigations.…”

“…Furthermore, some of these studies were contradictory, with some reporting no cardiovascular harm,11, 12 whereas others found e‐cigarettes to be harmful 13, 14. In support of the latter notion, several studies have shown that e‐cigarettes are associated with an increase in blood pressure, aortic stiffness, endothelial dysfunction, and oxidative stress 6, 13, 14, 15. Interestingly, a recent study reported that e‐cigarette–induced impairment of cardiovascular function in mice was similar to that triggered by conventional smoking, in which a comparable increase in aortic stiffness was observed 14…”

VpALI—Vaping-related Acute Lung Injury: A New Killer Around the Block

“…21,22 Both the solvent and the battery output voltage significantly affect levels of carbonyl compounds found in the aerosol. These compounds have been implicated in the development of oxidative stress and release of inflammatory mediators, 23,24 increasing cardiovascular risk [25][26][27] and platelet function alteration, 28 airway epithelial injury, and creating disturbances in gas exchange function. 29 Furthermore, repeated exposure of the heating element to high temperatures allows emission of nanoparticles 30 with a potential harmful effect on the respiratory system.…”

Electronic Cigarettes and Cardiovascular Risk: Caution Waiting for Evidence

“…This resulted in a 2.5-fold increase in aortic stiffness, a 24% lower maximal aortic relaxation in response to methacholine and a trend towards a reduction in left ventricular ejection fraction 97. Nonetheless, in humans, it seems that electronic cigarettes could be less harmful than standard cigarettes, as hypertensive patients who switched to electronic cigarettes benefited from a reduction in mean arterial blood pressure and improved pressure control 98. It should be emphasised that most of the data on the cardiovasculareffects of electronic cigarettes are derived from preclinical, crosssectional or small-sized clinical studies in which standard cigarettes were used as a comparison arm, thus providing limiting and conflicting results.…”