Division of Exercise Physiology, School of Medicine, West Virginia University , Morgantown, West Virginia.
Department of Physiology, Pharmacology, and Neurosciences, School of Medicine, West Virginia University , Morgantown, West Virginia.
J Appl Physiol (1985). 2018 Mar 1;124(3):573-582. doi: 10.1152/japplphysiol.00713.2017. Epub 2017 Nov 2.
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.
电子烟(E-cigs)的支持者声称,它们是烟草香烟的安全替代品;然而,人们对长期暴露于 E-cig 蒸汽对血管功能的影响知之甚少。本研究旨在确定慢性 E-cig 暴露的心血管后果。将雌性小鼠(C57BL/6 背景品系)随机分配至慢性每日 E-cig 蒸汽暴露、标准(3R4F 参考)香烟烟雾或过滤空气(每组 15 只)。相应的全身暴露由四个 1 小时暴露时间块组成,每个时间块之间间隔 30 分钟的新鲜空气休息时间,从而每天总共进行 4 小时,每周 5 天,共 8 个月。在三个时间点(暴露前、暴露中和暴露后)使用非侵入性超声心动图评估心脏功能和主动脉动脉僵硬度(AS),以脉搏波速度表示。在 8 个月的暴露完成后,使用体外张力肌动描记术和力转换来测量血管活性诱导化合物引起的胸主动脉张力变化。与空气暴露的对照小鼠相比,E-cig 和 3R4F 暴露的小鼠的 AS 分别增加了 2.5 倍和 2.8 倍(P < 0.05)。E-cig 和 3R4F 暴露的小鼠对甲酰胆碱的最大主动脉松弛作用分别降低了 24%和 33%(P < 0.05)。各组之间的硝普钠扩张无差异。3R4F 暴露在 8 个月后降低了射血分数和缩短分数,从而改变了心脏功能(P < 0.05)。E-cig 暴露也观察到类似但无统计学意义的趋势(P < 0.10)。组织学和呼吸功能数据支持 3R4F 暴露的肺气肿相关变化,但不支持 E-cig 暴露的变化。慢性 E-cig 蒸汽暴露会加速 AS,显著损害主动脉内皮功能,并可能导致心脏功能受损。这项研究的临床意义是,即使在相对低的暴露水平下,慢性使用 E-cigs 也会引起心血管功能障碍。新的和值得注意的是,电子烟(E-cigs)被宣传为安全的,但长期暴露于人体的情况还不够,不足以证明这些说法是合理的。这是第一项报告 8 个月 E-cig 蒸汽暴露对小鼠体内血管长期影响的研究(相当于人类 25 年的暴露)。我们报告说,E-cig 暴露会增加动脉僵硬度并损害正常的血管反应性,这与其他危险因素相似,包括吸烟,这些因素会导致心血管疾病的发展。