e-Cigarette Aerosol Reduces Left Ventricular Function in Adolescent Mice

Neczypor, Evan W; Saldana, Ty; Mears, Matthew J.; Aslaner, David M; Escobar, Yael-Natalie H; Gorr, Matthew W.; Wold, Loren E.

doi:10.1161/circulationaha.121.057613

Cited by 13 publications

(11 citation statements)

References 5 publications

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“…Concerns exist that EC use may be associated with the onset of various adverse health effects related to the cardiovascular (Bhatnagar 2016 ; Schweitzer, Wills, and Behner 2017 ) and lung diseases (Chun et al 2017 ; Moazed and Calfee 2017 ). Data in animals suggest that short-term or long-term exposures to EC aerosols might result in cardiovascular remodeling driven by PG/VG vehicles, with nicotine potentially playing a protective role (Neczypor et al 2022 ). Analyses of the variety and concentrations of EC aerosol toxicants infer that EC aerosol is less harmful than tobacco smoke (Azzopardi et al 2016 ); however, the presence of lower concentrations of tobacco-related toxicants indicates these substances are not likely to be risk-free.…”

Section: Introductionmentioning

confidence: 99%

Pulmonary effects of e-liquid flavors: a systematic review

Effah¹,

Taiwo

Baines

et al. 2022

Journal of Toxicology and Environmental Health, Part B

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Electronic cigarettes (ECs) are purported to be tobacco harm-reduction products whose degree of harm has been highly debated. EC use is considered less hazardous than smoking but is not expected to be harmless. Following the banning of e-liquid flavors in countries such as the US, Finland, Ukraine, and Hungary, there are growing concerns regarding the safety profile of e-liquid flavors used in ECs. While these are employed extensively in the food industry and are generally regarded as safe (GRAS) when ingested, GRAS status after inhalation is unclear. The aim of this review was to assess evidence from 38 reports on the adverse effects of flavored e-liquids on the respiratory system in both in vitro and in vivo studies published between 2006 and 2021. Data collected demonstrated greater detrimental effects in vitro with cinnamon (9 articles), strawberry (5 articles), and menthol (10 articles), flavors than other flavors. The most reported effects among these investigations were perturbations of pro-inflammatory biomarkers and enhanced cytotoxicity. There is sufficient evidence to support the toxicological impacts of diacetyl- and cinnamaldehyde-containing e-liquids following human inhalation; however, safety profiles on other flavors are elusive. The latter may result from inconsistencies between experimental approaches and uncertainties due to the contributions from other e-liquid constituents. Further, the relevance of the concentration ranges to human exposure levels is uncertain. Evidence indicates that an adequately controlled and consistent, systematic toxicological investigation of a broad spectrum of e-liquid flavors may be required at biologically relevant concentrations to better inform public health authorities on the risk assessment following exposure to EC flavor ingredients.

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Section: Introductionmentioning

confidence: 99%

Pulmonary effects of e-liquid flavors: a systematic review

Effah¹,

Taiwo

Baines

et al. 2022

Journal of Toxicology and Environmental Health, Part B

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“…Acute exposures (2 weeks) to e-cigs showed cardiac function changes via echocardiography. 25 This study showed that e-cig exposure for 3 hours a day for 14 days, similar to a casual-use model, 26 found no significant effects on ejection fraction, but did elicit significantly increased angiogenesis in mouse heart tissue and significantly increased collagen content, but not tissue fibrosis. 25 This study implies that acute e-cig exposure had no significant effect on contractile function or fibrosis but did induce cardiac angiogenesis.…”

Section: Effects On Myocardial Healthmentioning

confidence: 67%

“…26 Male adolescent mice following 3 months of e-cig use showed increased perivascular fibrosis in e-cig liquid without nicotine, further supported by increased, although nonsignificant, type I collagen. 26 This same study also showed that gene expression of Col1a1 and Col3a1 was increased following e-cig use with nicotine at 3 weeks, but was reversed by 3 months, suggesting that perhaps nicotine may play a protective role.…”

Section: Effects On Myocardial Healthmentioning

confidence: 90%

“…26 Adolescent mice exposed to e-cigs had reduced end-systolic elastance independent of nicotine concentration and reduced preload-recruitable stroke work in e-cigs with nicotine, indicative of reduced contractile capacity. 26 Male adolescent mice following 3 months of e-cig use showed increased perivascular fibrosis in e-cig liquid without nicotine, further supported by increased, although nonsignificant, type I collagen. 26 This same study also showed that gene expression of Col1a1 and Col3a1 was increased following e-cig use with nicotine at 3 weeks, but was reversed by 3 months, suggesting that perhaps nicotine may play a protective role.…”

Section: Effects On Myocardial Healthmentioning

confidence: 97%

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Electronic Nicotine Delivery Systems and Cardiovascular/Cardiometabolic Health

Mears

Hookfin

Bandaru

et al. 2023

Circulation Research

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The use of electronic nicotine delivery systems, specifically electronic cigarettes (e-cig), has risen dramatically within the last few years; the demographic purchasing these devices is now predominantly adolescents that are not trying to quit the use of traditional combustible cigarettes, but rather are new users. The composition and appearance of these devices has changed since their first entry into the market in the late 2000s, but they remain composed of a battery and aerosol delivery system that is used to deliver breakdown products of propylene glycol/vegetable glycerin, flavorings, and potentially nicotine or other additives. Manufacturers have also adjusted the type of nicotine that is used within the liquid to make the inhalation more palatable for younger users, further affecting the number of youth who use these devices. Although the full spectrum of cardiovascular and cardiometabolic consequences of e-cig use is not fully appreciated, data is beginning to show that e-cigs can cause both short- and long-term issues on cardiac function, vascular integrity and cardiometabolic issues. This review will provide an overview of the cardiovascular, cardiometabolic, and vascular implications of the use of e-cigs, and the potential short- and long-term health effects. A robust understanding of these effects is important in order to inform policy makers on the dangers of e-cigs use.

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“…This nicotine exposure model also exacerbated LV dysfunction and infarct size in Langendorff-perfused hearts undergoing ex vivo ischemia-reperfusion injury ( 55 , 56 ). Three months of exposure to electronic cigarette vapor containing 20.2 mg/mL of nicotine in male, adolescent FVB (Susceptible to the Friend leukemia virus B) mice induced LV systolic and diastolic dysfunction which were not present in adult mice or female, adolescent mice ( 57 ).…”

Section: Methodsmentioning

confidence: 99%

Nicotine and novel tobacco products drive adverse cardiac remodeling and dysfunction in preclinical studies

Fried

Oakes²,

Whitehead³

et al. 2022

Front. Cardiovasc. Med.

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BackgroundThe heart undergoes structural and functional changes in response to injury and hemodynamic stress known as cardiac remodeling. Cardiac remodeling often decompensates causing dysfunction and heart failure (HF). Cardiac remodeling and dysfunction are significantly associated with cigarette smoking. Although cigarette smoking has declined, the roles of nicotine and novel tobacco products (including electronic cigarettes and heat-not-burn tobacco) in cardiac remodeling are unclear. In this perspective, we present evidence demonstrating maladaptive cardiac remodeling in nicotine-exposed mice undergoing hemodynamic stress with angiotensin (Ang)-II infusion and review preclinical literature linking nicotine and novel tobacco products with cardiac remodeling and dysfunction.MethodsAdult, male C57BL/6J mice were exposed to room air or chronic, inhaled nicotine for 8 weeks. A subset of mice was infused with Ang-II via subcutaneous osmotic mini-pumps during the final 4 weeks of exposure. Left ventricular structure and function were assessed with echocardiography.ResultsChronic, inhaled nicotine abrogated Ang-II-induced thickening of the left ventricular posterior wall, leading to reduced relative wall thickness. Ang-II infusion was associated with increased left ventricular mass index in both air- and nicotine-exposed mice.ConclusionsThese changes suggest a phenotypic shift from concentric hypertrophy to eccentric hypertrophy in nicotine-exposed, hemodynamically-stressed mice which could drive HF pathogenesis. These findings join a growing body of animal studies demonstrating cardiac remodeling and dysfunction following nicotine and electronic cigarette exposure. Further exploration is necessary; however, clinicians and researchers should not overlook these emerging products as potential risk factors in the pathogenesis of cardiac remodeling and associated diseases including HF.

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e-Cigarette Aerosol Reduces Left Ventricular Function in Adolescent Mice

Cited by 13 publications

References 5 publications

Pulmonary effects of e-liquid flavors: a systematic review

Pulmonary effects of e-liquid flavors: a systematic review

Electronic Nicotine Delivery Systems and Cardiovascular/Cardiometabolic Health

Nicotine and novel tobacco products drive adverse cardiac remodeling and dysfunction in preclinical studies

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