A single e-cigarette can be harmful to the body’s blood vessels

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Smoking e-cigarettes, also called vaping, has been marketed as a safe alternative to tobacco cigarettes and is rising in popularity among non-smoking adolescents.

However, a single e-cigarette can be harmful to the body’s blood vessels – even when the vapor is entirely nicotine-free – according to a new study by researchers in the Perelman School of Medicine at the University of Pennsylvania.

The results were published today in Radiology.

To study the short-term impacts of vaping, the researchers performed MRI exams on 31 healthy, non-smoking adults before and after vaping a nicotine-free e-cigarette.

Comparing the pre- and post-MRI data, the single episode of vaping resulted in reduced blood flow and impaired endothelial function in the large (femoral) artery that supplies blood to the thigh and leg.

Neurovascular response to breath hold. (a) Magnitude image intensity of superior sagittal sinus (SSS, box). Insets show velocity maps at different points of the velocity time-course (40 seconds [t40], 50 seconds [t50], and 70 seconds [t70]). (b) Sample SSS blood flow velocity time-course (red line) shown for a representative participant. The thick black line is linear fit during breath holds, the slope of which is the breath-hold index (BHI). ΔVSSS = post-breath hold relative velocity increase. Credit: Radiological Society of North America

The endothelium, which lines the inside surface of blood vessels, is essential to proper blood circulation.

Once the endothelium is damaged, arteries thicken and blood flow to the heart and the brain can be cut off, resulting in heart attack or stroke.

“While e-cigarette liquid may be relatively harmless, the vaporization process can transform the molecules – primarily propylene glycol and glycerol – into toxic substances,” said the study’s principal investigator Felix W. Wehrli, Ph.D., a professor of Radiologic Science and Biophysics.

“Beyond the harmful effects of nicotine, we’ve shown that vaping has a sudden, immediate effect on the body’s vascular function, and could potentially lead to long-term harmful consequences.”

E-cigarettes are battery-operated devices that convert liquid into aerosol, which is inhaled into the user’s lungs.

Typically, the liquid contains addictive nicotine, as well as flavors.

More than 10 million adults in the United States use e-cigarettes, and vaping has become especially popular among teenagers.

While there appears to be some consensus that vaping may be less harmful to health than tobacco cigarette smoking, the dangers of e-cigarettes remain unclear.

In this study, the researchers examined the impact of an e-cigarette that contained propylene glycol and glycerol with tobacco flavoring, but no nicotine, which study participants took 16, three-second puffs from.

To evaluate vascular reactivity, the group constricted the vessels of the thigh with a cuff and then measured how quickly the blood flowed after its release.

Using a multi-parametric MRI procedure, researchers scanned the femoral artery and vein in the leg before and after each vaping episode to see how vascular function changed.

Vaping impairs vascular function
Electronic cigarette components. Photograph shows the superior envelope (1), mouthpiece (2), light emitting diode (3), cylindrical 3.7-V lithium battery (4), wick and filament (5), thick wire (6), inner fibers (7), and outer fibers (8). Credit: Radiological Society of North America

The researchers then performed a statistical analysis to determine group differences in vascular function before and after vaping.

They observed, on average, a 34 percent reduction in the femoral artery’s dilation.

E-cigarettes exposure also led to a 17.5 percent reduction in peak blood flow, a 20 percent reduction in venous oxygen, and a 25.8 percent reduction in blood acceleration after the cuff release—the speed at which the blood returned to the normal flow after being constricted.

These findings suggest that vaping can cause significant changes to the inner lining of blood vessels, said study lead author Alessandra Caporale, Ph.D., a post-doctoral researcher in the Laboratory for Structural, Physiologic, and Functional Imaging at Penn.

E-cigarettes are advertised as not harmful, and many e-cigarette users are convinced that they are just inhaling water vapor,” Caporale said.

“But the solvents, flavorings and additives in the liquid base, after vaporization, expose users to multiple insults to the respiratory tract and blood vessels.”

Wehrli noted that they observed these striking changes after the participants (all of whom never smoked previously) used an e-cigarette a single time.

More research is needed to address the potential long-term adverse effects of vaping on vascular health, but he predicts that e-cigarettes are potentially much more hazardous than previously assumed. Earlier this year, for instance, his research group found that acute exposure to e-cigarettes causes vascular inflammation.

“I would warn young people to not even get started using e-cigarettes.

The common belief is that the nicotine is what is toxic, but we have found that dangers exist, independent of nicotine,” Wehrli said.

“Clearly if there is an effect after a single use of an e-cigarette, then you can imagine what kind of permanent damage could be caused after vaping regularly over years.”


Tobacco smoking has been demonstrated to be a major risk factor for heart failure and is associated with the morbidity in heart failure patients16, while the effect of electronic cigarette (e-cigarette) use is largely unknown.

E-cigarettes are interpreted in many societies as a safer alternative compared to combustible cigarettes (c-cigarettes) despite the fact that there is no sufficient evidence regarding e-cigarette safety and efficacy for replacing c-cigarettes711.

There are very few studies investigated the potential effect of e-cigarettes on cardiac function, and most of these studies are cell culture-based or small size clinical studies.

Patented in 2003 and extensively promoted in the U.S. for the past decade, e-cigarettes are estimated to become a $10 billion dollar industry12.

The marketing of e-cigarettes as a healthy alternative to c-cigarette smoking is associated with increased use of e-cigarettes among younger adolescents and current smokers who believe that e-cigarettes are not harmful1317.

Experimentally, some early studies showed that e-cigarette liquid or vapor were less toxic compared to c-cigarettes in cultured cardiac myocytes and endothelial cells1821.

A recent study using longitudinal within-subjects observational method showed that switching from c-cigarettes to e-cigarettes substantially reduced several carcinogens and toxicants such as the metabolites of 1,3-butadiene, benzene and acrylonitrile, while nicotine exposure remains unchanged22.

However, in other studies, it was found that significant amounts of formaldehyde and acetaldehyde in e-cigarette vapor, and at higher temperature, trace amount of acetone and acrolein were detectable23, suggesting some shared toxicity between e-cigarettes and c-cigarettes.

It was reported that e-cigarettes and associated flavoring agents may produce harmful effects in stem cells and gingival fibroblasts by generating aldehydes/carbonyls from e-cigarette vapor, resulting in protein carbonylation and DNA damage, as well as cellular senescence24.

Habitual e-cigarette use was found to shift cardiac autonomic balance toward sympathetic predominance and increased oxidative stress, which are associated with increased cardiovascular risk25.

These results raised questions regarding the safety of e-cigarette use and its beneficial effect as a substitute for c-cigarettes.

Our recent studies suggest that chronic exposure to e-cigarette vaping disrupts airway barrier function, induces tissue fibrosis in the heart and kidney, and causes systemic inflammation in mice26. In the current study, we investigated the acute effect of short-term exposure to e-cigarettes on cardiac function and tissue injury in mice.

Results

The effect of e-cigarette vaping on mouse cardiac function and bodyweight gain

We have previously demonstrated that c-cigarette smoking worsens cardiac and renal function in humans and in animal models27,28.

To study the effect of e-cigarette smoking on the cardiac functional change, we performed echocardiographic measurements on animals exposed to e-cigarette vapor.

The e-cigarette liquid was made of propylene glycol and glycerin at 1:1 ratio and contains 24 mg/ml nicotine.

E-cigarette vapor was generated using InExposure cigarette smoking system from SCIREQ as shown in Fig. 1 as described in Methods section.

The body weight of each mouse was measured every two days during the experiment and the percentage body weight change was calculated.

To determine the nicotine exposure level in these animals, we measured the plasma concentration of cotinine, a major metabolite of nicotine.

As shown in Fig. 2A, the cotinine concentration was about 3.95 ± 0.70 µM in e-cigarette-exposed mice, while it was not detectable in air-exposed mice. In body weight measurement, we found that e-cigarette vaping significantly inhibited the bodyweight gain (Fig. 2B).

This reduction in bodyweight gain was significant in both male and female mice compared to controls (Fig. 2C).

Echocardiographic data showed that e-cigarette vaping for 2 weeks significantly decreased the heart rate compared to the baseline, whereas the heart rate in air control groups had no significant differences (Fig. 3A).

E-cigarette vapor caused a modest decrease in ejection fraction compared to baseline but was not statistically significant (Fig. 3B).

There was no significant change in left ventricle chamber size and aorta dimension after e-cigarette exposure (Fig. 3C–E).

The heart weight in mice exposed to e-cigarette vapor (particularly the female mice) were lower compared to that in the air control group (103.6 ± 5.53 vs 97.61 ± 4.61 mg in female; 134.85 ± 4.6 vs 132.60 ± 4.12 in male), but had no statistical significance (Fig. 4A). The heart weigh/body weight (HW/BW) ratio showed a similar trend (Fig. 4B).

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Figure 1
Schematic presentation of the InExpose e-cigarette vaping system.

More information: “Acute Effects of Electronic Cigarette Aerosol Inhalation on Vascular Function Detected at Quantitative MRI.” RadiologyDOI: 10.1148/radiol.2019190562

Journal information: Radiology
Provided by Perelman School of Medicine at the University of Pennsylvania

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