Vaping Perpetuates Cardiac Electrical Instability

Abstract

BackgroundTobacco cigarette smoking is on the decline, but the usage of electronic nicotine delivery systems (ENDS) is gaining popularity, specifically in the teen and young adult age groups. While the cardiac toxicity of tobacco cigarette smoking has been widely studied and is well established, the possible cardiac toxicity of ENDS products and their design characteristics, such as added flavorings, are largely underexplored. Vaping, a form of electronic nicotine delivery, uses "e-liquid" to generate "e-vapor", a smoke-like aerosolized mixture of nicotine and flavors. Here, we tested the hypothesis that vaping results in cardiac electrophysiological instability and arrhythmogenesis. We thus investigated how e-liquids with different flavors affect cardiac in-vitro and in-vivo toxicity, in cell culture and in animals. MethodsThree e-liquids with vanilla, cinnamon or fruit flavors were studied. We quantified apoptosis and oxygen consumption rate in HL-1 cells cultured with e-vapors extracts. In human iPSC derived ventricular cardiomyocytes (hiPSC-CM) cultured with e-vapor extract, beating frequency and repolarization duration were measured using multiple electrode arrays (MEA). Mass spectrometry (GC-MS) was used to analyze the composition of the e-vapors. Telemetric ECGs were obtained in freely moving C57BL/6J mice exposed to vanilla flavored e-vapor for 10 weeks and heart rate variability was analyzed (HRV). In-vivo inducibility of ventricular tachycardia as well as optical mapping of voltage in isolated Langendorff-perfused hearts were also carried out. ResultsE-vapor caused a dose dependent increase in toxicity in Hl-1 myocytes and e-vapors containing vanilla and cinnamon flavorings, as indicated by GC-MS, were more toxic, and inhibited cellular respiration more than the fruit flavored e-vapor. In hiPSC-CM cultured with 25% cinnamon flavored e-vapor for 24 hours, beating frequency increased, and the field potential duration significantly increased compared to air control. Inhalation exposure to vanilla flavored e-vapor for 10 weeks caused significant effects on HRV. Additionally, inducible VT was significantly longer, and in optical mapping, the magnitude of ventricular action potential duration alternans was significantly larger in the exposed mice compared to control ConclusionThe widely popular flavored ENDS are not harm free, and they show potential toxicity to the heart, in-vitro, and in vivo. Further studies are needed to further assess their cardiac safety profile, and long-term health effects.