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IN VITRO AND IN VIVO CARDIAC TOXICITY OF FLAVORED ELECTRONIC NICOTINE DELIVERY SYSTEMS
American Journal of Physiology-Heart and Circulatory Physiology ( IF 4.1 ) Pub Date : 2020-11-20 , DOI: 10.1152/ajpheart.00283.2020
Obada Abouassali 1 , Mengmeng Chang 1 , Bojjibabu Chidipi 1 , Jose Luis Martinez 2 , Michelle Reiser 1 , Manasa Kanithi 1 , Ravi Soni 1 , Thomas V McDonald 3 , Bengt Herweg 3 , Javier Saiz 2 , Laurent Calcul 4 , Sami F Noujaim 1
Affiliation  

The usage of flavored electronic nicotine delivery systems (ENDS) is popular, specifically in the teen and young adult age groups. The possible cardiac toxicity of the flavoring aspect of ENDS is largely unknown. Vaping, a form of electronic nicotine delivery, uses "e-liquid" to generate "e-vapor", an aerosolized mixture of nicotine and/or flavors. We report our investigation into the cardio-toxic effects of flavored e-liquids. E-vapors containing flavoring aldehydes such as vanillin and cinnamaldehyde, as indicated by mass spectrometry were more toxic in HL-1 cardiomyocytes than fruit flavored e-vapor. Exposure of human induced pluripotent stem cells derived cardiomyocytes to cinnamaldehyde or vanillin flavored e-vapor affected the beating frequency and prolonged the field potential duration of these cells more than fruit flavored e-vapor. Additionally, vanillin aldehyde flavored e-vapor reduced the hERG current in transfected human embryonic kidney cells. In mice, inhalation exposure to vanillin aldehyde flavored e-vapor for 10 weeks caused increased sympathetic predominance in heart rate variability measurements. In vivo inducible ventricular tachycardia was significantly longer, and in optical mapping, the magnitude of ventricular action potential duration alternans was significantly larger in the vanillin aldehyde flavored e-vapor exposed mice compared to control. We conclude that the widely popular flavored ENDS are not harm free, and they have a potential for cardiac harm. More studies are needed to further assess their cardiac safety profile and long- term health effects.

中文翻译:


调味电子尼古丁输送系统的体外和体内心脏毒性



调味电子尼古丁输送系统 (ENDS) 的使用很受欢迎,特别是在青少年和年轻人年龄段。 ENDS 调味剂可能产生的心脏毒性在很大程度上尚不清楚。电子烟是电子尼古丁输送的一种形式,使用“电子液体”产生“电子蒸气”,即尼古丁和/或香料的雾化混合物。我们报告了对调味电子烟液的心脏毒性作用的调查。质谱分析表明,含有香草醛和肉桂醛等调味醛的电子烟对 HL-1 心肌细胞的毒性比水果味电子烟的毒性更大。将人类诱导多能干细胞衍生的心肌细胞暴露于肉桂醛或香草醛味的电子蒸汽中,与水果味的电子蒸汽相比,对这些细胞的搏动频率和场电位持续时间的影响更大。此外,香草醛风味的电子蒸汽降低了转染的人胚胎肾细胞中的 hERG 电流。在小鼠中,吸入香草醛味电子蒸气 10 周会导致心率变异性测量中交感神经优势增加。与对照组相比,暴露于香草醛醛风味电子蒸气的小鼠体内诱导的室性心动过速明显更长,并且在光学测绘中,心室动作电位持续时间交替的幅度显着更大。我们的结论是,广泛流行的调味电子尼古丁传送系统并非无害,而且有可能对心脏造成伤害。需要更多的研究来进一步评估其心脏安全性和长期健康影响。
更新日期:2020-11-22
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