Effects of using electronic cigarettes on nicotine delivery and cardiovascular function in comparison with regular cigarettes
Introduction
Cigarette smoking is a major health hazard, and contributes significantly to cardiovascular morbidity and mortality (Ambrose and Barua, 2004). According to the World Health Organization (WHO), smoking is the most preventable risk factor for cardiac and lung disease and is expected to cause 1 billion deaths during the 21st century. Studies have shown that acute smoking inhalation has significant adverse effects on left ventricular function in healthy smokers (Lichodziejewska et al., 2007). Smoking inhalation increases inflammation, thrombosis, and oxidation of low-density lipoprotein cholesterol that contributes to the cardiovascular dysfunction, such as defects in myocardial function (Farsalinos et al., 2013). Smoking also increases the risk of developing atherosclerosis, a disease which can cause heart attacks, strokes, and can even lead to death. The mechanisms by which cigarette smoking contributes to acute cardiovascular effects include (1) induction of a hypercoagulable state; (2) increased myocardial work; (3) CO mediated reduction in the oxygen-carrying capacity of the blood; (4) induction of endothelial dysfunction; (5) coronary vasoconstriction; and (6) catecholamine (Benowitz and Gourlay, 1997, Benowitz et al., 2002). There are many toxicants in cigarette smoke, such as CO, α, β-unsaturated aldehydes, superoxide, N2O, and other oxidant gases, which could contribute to heart disease. Heart disease is the main cause of morbidity and mortality in smokers, with 40% of deaths in smokers due to coronary artery disease alone (Deanfield et al., 1986).
Thus, Tobacco Harm Reduction strategies and products have been developed to reduce the amount of toxic substances that a smoker is exposed to while smoking. As an alternative for smokers, e-cigs are rapidly growing worldwide and are gaining significant attention as potentially reduced exposure products and smoking cessation products (Etter and Bullen, 2013, Polosa et al., 2011, Farsalinos and Polosa, 2014). Though only developed and marketed in recent years, e-cigs are already used by several millions of people worldwide. The device consists of a battery, a cartridge containing liquid and a heating element which is heated by the battery and evaporates the liquid. The liquid usually contains water, nicotine, glycerin, propylene glycol, and a variety of flavors. E-cigs simulate the effect of smoking by producing an inhaled aerosol and satisfy the behavioral aspects associated with smoking. Because e-cigs does not involve the combustion of the chemical components commonly found in tobacco cigarettes, it is expected that user exposure to the toxicants may be less so use of e-cigs could avoid many of the detrimental health effects attributed to cigarette smoking. Laboratory analyses of the e-liquids show that there are less harmful and potentially harmful constituents (HPHCs) than regular cigarettes (Burstyn, 2013). Most studies have found no nitrosamines in the vapor, but even in studies where nitrosamines were found, the levels detected were 500–1400 times less than the amount present in one tobacco cigarette (Cobb et al., 2010, Burstyn, 2013, Goniewicz et al., 2013, Kim and Shin, 2013).
As an emerging product developed recently, public health concerns have been raised globally about using of this smoking alternative. To date, there is little objective data that provide sound information on e-cigs toxicant content, the toxicant exposure level and the potential health effects to end users. Studies provided mixed data on plasma nicotine levels after use of e-cigs. One study found that in contrast to use of usual-brand cigarettes, use of e-cigs containing 16–18 mg/mL of nicotine did not increase nicotine plasma concentrations significantly from baseline (Vansickel et al., 2010). Other studies reported significant increases from baseline in nicotine plasma concentration after use of the usual-brand electronic devices (containing 9–24 mg/mL of nicotine), similar to conventional cigarette smoking (Vansickel and Eissenberg, 2013, Dawkins et al., 2013). These mixed results may reflect the differences in study design, or device characteristics, or suggest an acclimation to the product for new users.
Extremely limited studies have evaluated the effects of e-cigs on the hematology and cardiovascular system in relation to nicotine delivery. A study evaluated the acute effects of e-cigs and cigarette smoking on complete blood count markers in 30 human subjects and found cigarette smoking increased white blood cell, lymphocyte, and granulocyte counts for at least 1 h in smokers and never smokers, but the e-cigs smoking did not influence the complete blood count (Flouris et al., 2012). A clinical study examined the acute effects of e-cigs and regular cigarettes on nicotine delivery profile and cardiovascular function. It was observed that regular cigarettes significantly increased the plasma nicotine and CO concentration and heart rate within the first 5 min of administration, whereas e-cigs did not (Vansickel et al., 2014). Farsalinos et al. (2014) found that smoking one tobacco cigarette led to significant acute myocardial dysfunction but e-cigs had no acute adverse effects on cardiac function. The researchers reported that smoking a tobacco cigarette had important hemodynamic consequences, with significant increases in heart rate, systolic and diastolic blood pressure. In contrast, e-cigs produced only a slight elevation in diastolic blood pressure. The nicotine level in the e-cigs reported in the Farsalinos study was 1.1% in the liquid. The authors concluded nicotine in e-cigs was absorbed at a lower rate compared to regular cigarette smoking and e-cigs did not show to have adverse effects on the heart (Farsalinos et al., 2014).
The nicotine concentrations tested in above studies, were relatively considered to be “low-medium”, with short duration of exposure. Given the fact that there is wide range of nicotine concentrations in the e-liquid of currently marketed e-cigs, and the amount of regular and electronic cigarettes consumed can be very different from smoker to smoker and from day to day, this clinical study was designed to characterize blu e-cigs users’ nicotine exposure, and to investigate the acute effects of blu e-cigs with higher nicotine level (up to 2.4% in the e-liquid) and longer duration (up to 1.5 h) on the hemodynamic effects (blood pressure and heart rate) in relation to internal nicotine dose, compared to the adverse effects of regular smoking.
Section snippets
Participants
The study was approved by the Institutional Review Board (IRB) of Chesapeake Research Review Inc. (CRRI, Columbia, MD). Thirty-eight subjects underwent the screening procedures to ensure that they met the requirements for inclusion within 28 days prior to participation in the study. The IRB-approved informed consent form (ICF) was collected from all participants prior to completion of the screening or other study procedures. Fourteen subjects withdrew from the study. The remaining 23
Study population
The demographic characteristics of the study population are presented in Table 1. Twenty-three subjects (11 male and 12 female) properly completed the study and their data were included in the analyses. The average age of this study population was 39 years with a standard deviation of about 11. The youngest was 23 and oldest was 58 years old. Most of subjects were white (83%), with 13% African American, and 4% of American Indian. Their body weight averaged at 78.8 kg with a standard deviation of
Discussion
The key objectives of this study was to characterize e-cig users’ plasma nicotine levels, and to investigate and compare the acute effects of blu e-cigs with high nicotine level (up to 2.4% in e-liquid) and long duration (up to 1.5 h) on hemodynamic effects, with those of regular cigarette smoking.
Two types of exposures were utilized: a single controlled administration and a short-term ad lib use. The controlled administration consisted of 50 puffs of the assigned e-cig product (5-s puffs at
Conclusion
This study showed that after half hour controlled and 1 h ad lib product use, the nicotine plasma concentrations (C90) were statistically significantly lower in e-cigarette users than in Marlboro® cigarette users. Among the blu e-cigarettes, the concentrations of nicotine in the e-liquid correspond to the nicotine plasma nicotine levels (C90) after 1.5 h of product use. 2.4% nicotine in the e-liquid of e-cigarettes delivered higher nicotine in plasma that 1.6% (e.g., C90 = 22.41 ng/mL of e-cig 2.4%
Acknowledgments
This study was conducted in Celerion (Lincoln, Nebraska), funded by the LOEC, Inc. d/b/a blu ecigs.
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