Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida.
Ci2 B, Universitat Politècnica de València, Valencia, Spain.
Am J Physiol Heart Circ Physiol. 2021 Jan 1;320(1):H133-H143. doi: 10.1152/ajpheart.00283.2020. Epub 2020 Nov 20.
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 cardiotoxic 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 cell-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. In addition, vanillin aldehyde-flavored e-vapor reduced the human ether-à-go-go-related gene (hERG)-encoded potassium current in transfected human embryonic kidney cells. In mice, inhalation exposure to vanillin aldehyde-flavored e-vapor for 10 wk 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 than in controls. 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. The use of electronic nicotine delivery systems (ENDS) is not harm free. It is not known whether ENDS negatively affect cardiac electrophysiological function. Our study in cell lines and in mice shows that ENDS can compromise cardiac electrophysiology, leading to action potential instability and inducible ventricular arrhythmias. Further investigations are necessary to assess the long-term cardiac safety profile of ENDS products in humans and to better understand how individual components of ENDS affect cardiac toxicity.
使用调味电子烟（ENDS）非常普遍，尤其是在青少年和年轻成年人中。ENDS 调味成分可能具有心脏毒性，但目前尚不清楚。电子烟是一种电子尼古丁输送方式，使用“电子液体”产生“电子蒸汽”，这是一种尼古丁和/或调味剂的气溶胶混合物。我们报告了对调味电子烟液心脏毒性的研究。质谱分析表明，含有香草醛和肉桂醛等调味醛的电子蒸汽比水果味电子蒸汽毒性更大。与人诱导多能干细胞衍生的心肌细胞接触肉桂醛或香草醛调味电子蒸汽会影响这些细胞的搏动频率，并延长其场电位持续时间，超过水果味电子蒸汽。此外，香草醛调味电子蒸汽会降低转染的人胚肾细胞中编码人 ether-à-go-go 相关基因（hERG）的钾电流。在小鼠中，吸入 10 周香草醛调味电子蒸汽会导致心率变异性测量中交感神经优势增加。在体内，可诱导性室性心动过速的持续时间明显更长，在光学标测中，香草醛调味电子蒸汽暴露组的心室动作电位时程交替幅度明显大于对照组。我们得出结论，广泛流行的调味电子烟并非无害，它们可能对心脏造成危害。需要进一步研究来评估它们的心脏安全性和长期健康影响。使用电子尼古丁输送系统（ENDS）并不安全。目前尚不清楚 ENDS 是否会对心脏电生理功能产生负面影响。我们在细胞系和小鼠中的研究表明，ENDS 会损害心脏电生理功能，导致动作电位不稳定和可诱导性室性心律失常。需要进一步研究来评估人类使用 ENDS 产品的长期心脏安全性，并更好地了解 ENDS 的各个成分如何影响心脏毒性。
