572 I. Szołtysek-Bołdys i wsp.

PRACE ORYGINALNE

Influence of inhaled nicotine source on arterial stiffnessZmiana sztywności tętnic w zależności od źródła inhalowanej nikotyny

1Department of General and InorganicChemistry, School of Pharmacy, Medical University of Silesia, Sosnowiec, Poland; Head of the Department: Prof. Andrzej Sobczak

2Department of Chemical Hazards and Genetic Toxicology, Institute of Occupational Medicine and Environmental Health,Sosnowiec, Poland; Director of the Institute: Piotr Z. Brewczyński M.D., Ph.D.

3Students’ Research Society at the Department of General and Inorganic Chemistry, School of Pharmacy, Medical University of Silesia, Sosnowiec, PolandHead of the Department: Prof. Andrzej Sobczak

4Battelle Memorial Institute, Human Exposure Assessment Laboratory (HEAL), Baltimore, MD, USA

Additional key words:arterial stiffnessnicotineelectronic cigarettestobacco smoke

Dodatkowe słowa kluczowe:sztywność tętnicnikotynaelektroniczne papierosydym tytoniowy

Declaration of interestsAS received research funds and travel expenses from Chic Group LTD, manufacturer of electronic cigarettes in Poland. Other authors declare no conflict of interest

This work was supported by internal funding from the Institute of Occupational Medicine and Environmental Health, Poland (ZSChiTG5) and Medical University of Silesia, Poland (KNW-1-019/N/4/0).

Adres do korespondencji:Prof. Andrzej SobczakDepartment of General and InorganicChemistry, School of Pharmacy, Medical University of Silesia, Jagiellonska St. 4, 41-200 Sosnowiec, Poland tel/fax: 32 364 1564e-mail: asobczak@sum.edu.pl

Izabela SzołtySek-BołdyS1

Andrzej SoBczak1,2

Wioleta zielińSka-danch1

Aleksandra Bartoń3

Bartosz koSzowSki4

Leon kośmider1,2

Introduction: Tobacco smoking leads to changes in hemodynamic parameters such as heart rate and systolic or diastolic blood pressure. It has a direct influence on the elasti-city of blood vessels and increases arterial stiffness, which can result in development of atherosclerosis. Data show that the nicotine in tobacco smo-ke probably is responsible for these changes.

Electronic cigarettes (e-cigarettes) were supposedly a healthier alternati-ve to combustible cigarettes because they imitate a process of cigarettes smoking but generate nicotine aerosol without the toxic substances from to-bacco combustion. However, the use of e-cigarettes is still controversial because their toxicity, safety and long term use health impact have not been sufficiently studied.

Aim: The aim of this study was to evaluate changes in arterial stiffness parameters after smoking a cigarette or e-cigarette use.

Methods: Fifteen healthy women, aged 19–25 years old, smoking ≥5 cigarettes per day for at least two years participated in the study. A non-invasive measurement of arterial stiffness parameters – Stiffness Index (SI) and Reflection Index (RI) – was conducted and systolic and diastolic blood pressure and heart rate were measured before and after smoking a conventional cigarette as well as use of an e-cigarette.

Results: Statistically significant changes in the SI and RI were obse-rved before and after smoking of a conventional cigarette [SI: 6.75m/s (6.66 – 6.85, 95% CI) vs 6.56m/s (6.46 – 6.65. 95% CI), p=0.0056; RI: 54.0% (51.5 – 56.7, 95% CI) vs 49.6% (47.5 – 51.8, 95% CI), p=0.010]. The use of e-cigarettes resulted in no statistically significant changes in the SI and RI. After both product use systolic and diastolic blood pressure and heart rate increased but the changes were not statistically significant.

Conclusions: In contrast to conven-tional cigarette use, the use of elec-tronic cigarettes causes no changes in arterial stiffness. This may indicate

Wstęp: Palenie tytoniu prowadzi do zmian parametrów hemodynam-icznych takich jak ciśnienie skurc-zowe, rozkurczowe, puls ale przede wszystkim w sposób bezpośredni odbija się na stanie elastyczności naczyń krwionośnych, powodując wzrost sztywności tętnic. Może to prowadzić do zmian miażdżycowych w ich obrębie. Uważa się, że za te zmiany w głównym stopniu odpowiedzialna jest prawdopodobnie nikotyna obecna w dymie tytoniowym. Alternatywą dla papierosów konwencjonalnych miały być papierosy elektroniczne (e-papierosy), które generują aero-zol zawierający nikotynę, bez sub-stancji będących wynikiem spalania tytoniu, imitując w ten sposób papie-rosa konwencjonalnego. Produkty te nie są jednak odpowiednio przeba-dane pod względem toksyczności i bezpieczeństwa ich stosowania, a ich używanie jest wciąż kontrowersyjne.

Cel pracy: Celem prezentowanej pracy była ocena zmian parametrów sztywności tętnic pod wpływem dymu tytoniowego oraz aerozolu generow-anego z e-papierosa.

Metodyka: Na podstawie ankiet, do badań wytypowano grupę 15 zdrowych kobiet w wieku 19-25 lat, wypalających minimum 5 papierosów dziennie przez co najmniej 2 lata. Wykonano bezinwazyjny pomiar parametrów sztywności tętnic - indeksu sztywności (SI) i odbicia (RI) oraz ciśnienia skurc-zowego, rozkurczowego i tętna. Bada-nia przeprowadzono przed i po wypale-niu papierosa konwencjonalnego oraz przed i po wypaleniu e-papierosa.

Wyniki: Znamienne statystycznie zróżnicowanie wartości SI i RI zaobser-wowano jedynie przed i po wypaleniu papierosa konwencjonalnego. Wartość średniej arytmetycznej SI wynosiła odpowiednio 6,75m/s (6,66 – 6,85; 95% CI) vs 6,56m/s (6,46 – 6,65; 95% CI), p=0,0056 natomiast wartość średniej arytmetycznej RI 54,0% (51,5 – 56,7; 95% CI) vs 49,6% (47,5 – 51,8; 95% CI), p=0,010. Użycie e-papierosa nie powodowało istotnych statystycznie zmian wartości SI i RI. W obu przy-padkach zwiększało się nieznacznie ciśnienie skurczowe i rozkurczowe

573Przegląd Lekarski 2014 / 71 / 11

lower bioavailability of nicotine from the e-cigarette or an additional effect of other substances present in cigarette smoke but absent in an e-cigarette aerosol.

oraz tętno, ale zmiany były nieznamienne.Wnioski: Używanie papierosów elektronicznych, w

przeciwieństwie do papierosów konwencjonalnych, nie wpływa na zmianę sztywności tętnic, co może wskazywać na mniejszą efektywność w biodostępności nikotyny z e-papierosa lub dodatkowy wpływ, na sztywność tętnic innych substancji obecnych w dymie papierosowym, a nieobecnych w aerozolu z e-papierosa.

Introduction In addition to hemostasis, endothelium

and lipid metabolism dysfunctions, the dy-namic properties of the arteries’ walls play an important role in pathogenesis of tobacco smoking induced coronary artery diseases. Scientific data show that smoking even a single cigarette immediately impairs elastic properties of large and medium arteries [1]. Rhee et al. reported that smoking a cigarette rapidly changed heart rate wave shape and increased heart rate and blood pressure in smokers with and without hypertension [2]. It has been indicated that even passi-ve exposure to tobacco smoke for 1 hour results in statistically significant increase in systolic blood pressure and changes in the heart rate wave shape in young men [3]. kallio et al. found a positive correlation between serum cotinine concentration and arterial stiffness in children [4]. Study of 554 smokers, former smokers, and non-smokers published by Jatoi et al. indicate that there is a linear relationship between the duration of addiction and changes in the pulse wave graph, even after correction values for age, sex, blood pressure, heart rate and BMI [5]. While a correlation between exposure to tobacco smoke (active and passive), and the cardiovascular system disorders, including changes in arterial stiffness are indisputable [6], the effect of nicotine on arterial stiffness remains unclear. This problem becomes par-ticularly important in terms of the electronic cigarettes safety assessment. The rapid spread of e-cigarette market, while there is a lack of sound scientific research related to their safety, carries serious implications for their potential impact on the users’ health. By now, there is insufficient data on the benefits that e-cigarette use might bring in the process of smoking cessation as well as their overall health effects [7]. The report prepared for the World Health Organization (WHO) Tobacco Free Initiative by team of experts in the field of tobacco research calls for a studies assessing short- and long-term health effects of e-cigarette use [8]. The research on the risk of developing cardiovascular diseases is particularly im-portant because of the nicotine content in e-cigarette aerosol [9].

The present study was an initial attempt to compare how aerosol generated from e-cigarettes and tobacco smoke influence changes arterial stiffness parameters: Stiff-ness index (Si) and reflection index (ri).

Materials and Methods ParticipantsEligibility was determined through a

screening visit in which smoking history was documented. Healthy students of the Medical University of Silesia who smoked at least 5 cigarettes per day for at least two

years were enrolled in the study. All partici-pants reported using e-cigarettes at least 10 times. Exclusion criteria were: 1) age under 18 years old; 2) hypertension (blood pressure >140/90 mmHg) or other circular system diseases; 3) cancer; 4) hypercho-lesterolemia (total cholesterol>200 mg/dL); 5) diabetes; 6) pregnancy or lactation; 7) current use of estrogens or progestins or other hormones; 8) heart medications; 9) use of nicotine replacement therapy; and 10) general health problems (chronic bron-chitis, asthma, etc.). Participants were not compensated for participating in the study. All participants signed an informed consent form approved by the Bioethics Commit-tee of the Medical University of Silesia (knw/0022/kB1/174/i/09/10).

Tobacco productsDuring the study participants used either

their regular combustible cigarettes or used e-cigarettes with e-liquid supplied by the research team. We used the most common on the Polish market Ego-3 e-cigarettes (Volish Ltd, Poland), which was also used in our previous study [10]. The Ego-3 con-sists of clearomizer Crystal 2 with heating coil of 2.4 Ohm resistance and stabilized voltage battery (900 mAh, 3.4V). Batteries were fully charged for 24h before each use. Participants used 24 mg nicotine/mL e-liquid during experiments. nicotine content in the aerosol generated in laboratory conditions using the automatic smoking machine Pa-laczbot® [11] was 0.77±0.12 mg (15x70 mL puffs, 1.8 sec. puff durations, and 17 sec. puff intervals).

Participants used filtered, ‘slim’ type combustible cigarettes defined by the ma-nufacturer to have a nicotine content of 0.7 mg per cigarette.

Study design The study employs a within-subject

crossover research design with one day washout period. Every participant visited the laboratory for two experimental sessions:

- Session 1: participant smoked a co-nventional cigarette taking 10 to 12 puffs;

- Session 2: participant vaped an e-cigarette taking 15 puffs.

Sessions 1 and 2 lasted about 1 hour each and were separated by at least one day. Upon arrival participants signed con-sent form and completed questionnaires. The Fagerstrom test for nicotine depen-dence (Ftnd) was used to assess depen-dence on nicotine [12]. All participants were asked to refrain from the use of tobacco or consumption of caffeine containing bever-ages for at least 12 hours before either laboratory visit. They were also asked not to have any meals at least 3 hours before participating in the experiment. The eligibility criteria were confirmed by measuring the carbon monoxide concentration in exhaled

air. Volunteers with a carbon monoxide con-centration >7 ppm were rescheduled. At the beginning of the experiment, the participants rested for 15 minutes in a reclined position. Arterial stiffness was then measured (Heart rate trance Pca2 micromedical, Uk). the stiffness index (Si) and reflection index (ri) were collected over 10 minutes (10s of measurement with 50s intervals; 10 mea-surements total). The heart rate and blood pressure were then measured (M3 Omron, Omron Healthcare Europe, Japan) accor-ding to recommendations by the European Society of Hypertension (two measurements with one minute intervals). Exhaled carbon monoxide was measured (MicroCO Micro medical, Uk). then participants smoked their regular combustible cigarette or e-cigarette (supplied by the research team). Both cigarette smoking and e-cigarette use occurred outside of the laboratory. The participants were observed by the research staff and use topography (number of puffs) were recorded. 10 minutes after finishing tobacco product use the arterial stiffness, heart rate, and blood pressure were me-asured again according to the procedure described above.

Dependent measuresArterial stiffnessThe measurement of arterial stiffness

was based on the analysis of the pulse wave graph by using a photoplethysmography method. The measurement was conducted at the height of the phalanges artery. The change in the amount of infrared light ab-sorbed by the hemoglobin present in the blood flow was detected. there is a greater blood volume during contraction of the car-diac muscle in the phalanges artery which results in an increased absorption of infrared radiation. in contrast, blood flow through the artery is reduced during cardiac diastole, which results in a reduced absorption of the emitted infrared [13,14]. The infrared source was a photodiode and the radiation was detected by infrared sensor located on the finger of the participant. the tension of small arteries affects the height of the diastolic component. The stiffness of large arteries affects the pulse wave velocity, and thus the rate of return of the reflected wave which determines the distance between the peak systolic and diastolic component on the pulse wave graph. SI is the ratio of the patient height (in meters) and the time between peaks of the systolic and diastolic components. SI allows evaluation of large artery stiffness and is related to the carotid-femoral pulse wave velocity, which changes with blood pressure and age. RI is the ratio of diastolic and systolic components heights (expressed in percentages). The height of the diastolic component reflects the amount

574 I. Szołtysek-Bołdys i wsp.

Figure 1Stiffness and Reflexion Indexes in women before and after smoking conventional cigarette and using e-cigarette. Whiskers represent 95% confidence intervals; ns, no significance changes were found.Zmiana indeksu sztywności i indeksu odbicia tętnic u kobiet wypalających papierosa konwencjonalnego i używających e-papierosa. Pionowe słupki oznaczają 95% przedział ufności; ns - nieznamienne statystycznie.

of the blood pressure reflection related to the tension of small arteries, which is a good indicator of small arteries tension [13-16].

During arterial stiffness measurements multiple factors can lead to misrepresenta-misrepresenta-tion of the results. To reduce error, a patient should rest in a supine position for a few minutes in silence, in a room with moderate temperature, lighting and sound. Such con-ditions were provided to all participants for the presented study.

Statistical analysis The normal distribution of the results

was confirmed by a Shapiro-Wilk test. Statistical analysis was performed using an F-test, p (anoVa). the statistical package STATISTICA 9.1 (Stat Soft, Inc. USA) was used for calculations.

Results ParticipantsParticipants were women aged 19 to

25 years (mean 23±2). They smoked 8±4 cigarettes per day for 4±2 years. Partici-pants’ BMI ranged 18.6 – 24.4 kg/m2 (mean 20.5±2.2). average Ftnd score was 3±1, which means the participants were “not or low dependent” on nicotine.

Arterial stiffnessStatistically significant differences in

the SI and RI values were observed only before and after smoking a conventional cigarette. SI arithmetic mean was 6.75 m/s (6.66 – 6.85, 95% CI) vs 6.56 m/s (6.46 – 6.65. 95% CI), p=0.0056, respectively, while RI arithmetic mean was 54.0% (51.5 – 56.7, 95% CI) vs 49.6% (47.5 – 51.8, 95% CI), p=0.010, respectively. The use of e-cigarettes resulted in no statistically significant changes in Si and ri. Si was 6.73 m/s (6.62 – 6.84, 95% CI) vs 6.75 m/s (6.66 – 6.83, 95% CI) respectively, while RI was 52.0% (49.3 – 54.7, 95% CI) vs 50.8% (48.2 – 53.3, 95% CI), respectively (Fig. 1). Both the conventional cigarette smoking and the use of e-cigarettes lead to a slight, but not statistically significant, increase in systolic blood pressure, diastolic blood pressure and heart rate (Fig. 2).

Discussion The toxic effect of tobacco smoke exten-

sively affects the condition of the circulatory system through loss of large artery wall elasticity. To assess the exposure to tobacco smoke, multiple biomarkers are used, which include some functional changes in the smoker’s vitals (e.g. systolic and diastolic blood pressure and heart rate) caused by tobacco smoke components, including nicotine. In the presented study, we found non-statistically significant increase in these parameters after the combustible cigarette smoking as well as after the e-cigarette use. The data are similar to other authors findings. namely, Farha et al. [17] reported an increase of all of the above mentioned hemodynamic parameters after the co-nventional cigarette smoking. However, a statistically significant difference was found only in heart rate change. czogała et al. [18] reported similar results. Both research teams studied the change in heart rate, systolic and diastolic blood pressure after

the e-cigarette use and they found no stati-stically significant changes in the analyzed parameters.

An important element of our study was the measurement of the SI and RI exposure biomarkers. According to guidelines publi-shed in 2006 on non-invasive methods of assessing the stiffness of large arteries, it is recommended to consider arterial stiffness in both local and systemic aspects and to perform pulse wave reflection assessment [19]. our study confirms a number of earlier reports on the influence of active smoking, which contributes to increased risk of car-diovascular morbidity via arterial stiffness [2,3,9]. We found statistically significant changes in SI and RI after smoking even a single cigarette.

The effect of nicotine on arterial stiffness remains unclear. There are very few scien-tific publications on this issue. The study involving 15 healthy young men showed significant changes in arterial stiffness after administering a single nicotine sublingual tablet (2 mg). The increase in blood nicotine concentration was similar to concentrations achieved after passive exposure to tobacco smoke [20]. In our study, the administra-tion of nicotine with e-cigarettes caused no significant changes in arterial stiffness parameters regardless of the fact that, theoretically, the participants inhaled similar dose of nicotine form both products (0.70 versus 0.77 mg per session for cigarettes and e-cigarettes, respectively). However, the changes in SI and RI were convergent

with those we found after smoking a com-bustible cigarette. Our results are limited by several factors. First, the study group was small (but homogeneous in terms of gender, age and BMI). Moreover, participants were low dependent on nicotine (according to Ftnd results) what might have contributed to cigarette smoking/e-cigarette use during sessions (small volumes of smoke/aerosol might have been inhaled and as a result small amounts of nicotine were delivered to the lungs).

Secondly, nicotine content in e-cigarette aerosol was determined by a machine smo-king using topography parameters recorded in e-cigarette participants from our previous study (15 puffs, 70 mL puff volume, 1.8 sec. puff duration, and 17 sec. puff intervals) [10]. In current study the number of puffs per e-cigarette use session was similar (15 puffs). However, other use topography parameters were not recorded and might have varied. Finally, recent studies indicate that the bio-availability of nicotine delivered with tobacco smoke is different than nicotine delivered with e-cigarette aerosol. Farsalinos et al. [21] found that plasma concentration of nicotine in smokers 5 minutes after conventional cigarette smoking is 185 to 286% higher than after e-cigarette use. Therefore, a reason why we observed no statistically significant changes in arterial stiffness after e-cigarette use could be due to inefficiency of the device in nicotine delivery compared to the combustible cigarette. However, the possibility of synergistic interaction of other

575Przegląd Lekarski 2014 / 71 / 11

compounds and nicotine in cigarette smoke which together lead to changes in arterial stiffness parameters cannot be excluded. it is indirectly confirmed in the recent study published by Farsalinos et al. [22] where the acute effects of e-cigarette use on myo-cardial function was examined. no adverse effects on left ventricular myocardial function were observed after using e-cigarettes for 7 minutes with nicotine-containing liquid. On the contrary, significant changes in diastolic function parameters were found after smok-ing one conventional cigarette.

ConclusionThe results obtained in our study do not

allow for a clear assessment of the effects of nicotine delivered with e-cigarette on arterial

stiffness among young women. However, considering the fact that the assessment of transitory arterial stiffness is an important indicator of the blood vessels condition and the possible risk of cardiovascular events, further research using this method to monitor the influence of nicotine on smokers’ health is justifiable.

References1. Mahmud A, Feely J: Effect of smoking on arterial stif-

fness and pulse pressure amplification. Hypertension 2003; 41: 183-187.

2. Rhee MY, Na SH, Kim YK, Lee MM, Kim HY: Acute effects of cigarette smoking on arterial stiffness and blood pressure in male smokers with hypertension. Am J Hypertens. 2007; 20: 637-641.

3. Mahmud A, Feely J: Effects of Passive smoking on blood pressure and aortic pressure waveform in

Figure 2 Systolic blood pressure, diastolic blood pressure and heart rate in women before and after smoking co-nventional cigarette and using e-cigarette. Whiskers represent 95% confidence intervals; ns, no significance changes were found; BP, blood pressure.Zmiana ciśnienia skurczowego, rozkurczowego krwi oraz tętna u kobiet wypalających papierosa konwencjonalnego i używających e-papierosa. Pionowe słupki oznaczają 95% przedział ufności; ns - nieznamienne statystycznie; BP - ciśnienie krwi

healthy Young adults - influence of gender. Br J Clin Pharmacol. 2003; 57: 37-43.

4. Kallio K, Jokinen E, Hämäläinen M, Saarinen M, Volanen I. et al: Decreased aortic elasticity in healthy 11-year-old children exposed to tobacco smoke. Pediatrics 2009; 123: 267-273.

5. Jatoi NA, Jerrard-Dunne P, Feely J, Mahmud A: Impact of smoking and smoking cessation on arterial stiffness and aortic wave reflection in hypertension. Hypertension 2007; 49: 981-985.

6. Barnoya J, Glantz SA: Cardiovascular effects of secondhand smoke: nearly as large as smoking. Circulation 2005; 111: 2684-2698.

7. Drummond MB, Upson D: Electronic cigarettes. Potential harms and benefits. Ann Am Thorac Soc. 2014; 11: 236-242.

8. Grana R, Benowitz NL, Glanz SA: Background Paper on E-cigarettes (Electronic Nicotine Delivery Systems) Center for Tobacco Control Research and Education University of California, San Francisco WHO Collaborating Center on Tobacco Control. Prepared for World Health Organization Tobacco Free Initiative 2013.

9. Lippi G, Favaloro EJ, Meschi T, Mattiuzzi C, Bor-ghi L, Cervellin G: E-cigarette and cardiovascular risk: beyond science and mysticism. Semin Thromb Hemost. 2014; 40: 60-65.

10. Kosmider L, Sobczak A, Fik M, Knysak J, Zaciera M. et al: Carbonyl Compounds in Electronic Cigarette Vapors-Effects of Nicotine Solvent and Battery Output Voltage. Nicotine Tob Res. 2014. doi:10.1093/ntr/ntu078.

11. Goniewicz MŁ, Kuma T, Gawron M, Knysak J, Kosmider L: Nicotine levels in electronic cigarettes. Nicotine Tob Res. 2013; 15: 158-166.

12. Heatherton TF, Kozlowski LT, Frecker RC, Fa-gerstrom KO: The Fagerstrom Test for Nicotine Dependence: a revision of the Fagerstrom Tolerance Questionnaire. Br J Addict. 1991; 86: 1119-1127.

13. Millasseau SC, Ritter JM, Takazawa K, Chowien-czyk PJ: Contour analysis of the photoplethysmo-grapic pulse measured at the finger. J Hypertens. 2006; 24: 1449-1456.

14. Avolio A: The finger volume pulse and assessment of arterial properties. J Hypertens. 2002; 20: 2341-2343.

15. Millasseau SC, Kelly RP, Ritter JM, Chowienczyk PJ: Determination of age-related increases in large artery stiffness by digital pulse contour analysis. Clin Sci. 2002; 103: 371-377.

16. Takazawa K, Tanaka N, Fujita M, Matsuoka O, Saiki T. et al: Assessment of vasoactive agents and vascular aging by the second derivative of photoplethysmogram waveform. Hypertension 1998; 32: 365-370.

17. Farha KA, Farha RA, Bolt M: The acute impact of smoking one cigarette on cardiac hemodynamic parameters. Cardiol Res. 2011; 2: 58-65.

18. Czogała J, Cholewiński M, Kutek A, Zielińska-Danch W: Evaluation of changes in hemodynamic parameters after the use of electronic nicotine deli-very systems among regular cigarette smokers. [in polish]. Przegl Lek. 2012; 69: 841-845.

19. Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C: European Network for Non-invasive Investigation of Large Arteries. Expert consensus document on arteria stiffness: methodological issues and clinical applications. Eur Heart J. 2006; 27: 2588-605.

20. Adamopoulos D, Argacha JF, Gujic M, Preumont N, Degaute JP, van de Borne P: Acute effects of nicotine on arterial stiffness and wave reflection in healthy young non smokers. Clin Exp Pharmacol Physiol. 2009; 36: 784-789.

21. Farsalinos KE, Spyrou A, Tsimopoulou K, Stefopo-ulos C, Romagna G, Voudris V: Nicotine absorption from electronic cigarette use: comparison between first and new-generation devices. Sci Rep. 2014; 4: 4133. doi: 10.1038/srep04133

22. Farsalinos KE, Tsiapras D, Kyrzopoulos S, Savvo-poulou M, Voudris V: Acute effects of using an elec-tronic nicotine-delivery device (electronic cigarette) on myocardial function: comparison with the effects of regular cigarettes. BMC Cardiovasc Disord. 2014; 14: 78. doi: 10.1186/1471-2261-14-78.