Synthetic Coolants WS-3 and WS-23 Triple Premature Heartbeats in Mice Exposed to Nicotine Aerosols

Researchers exposed mice to e-cigarette aerosols with nicotine plus WS-3 or WS-23 and recorded ECGs during inhalation; human iPSC-derived cardiomyocytes received the same coolants plus noradrenaline. WS-23 produced the largest rise in premature ventricular contractions, shortened QT intervals, and elevated heart-rate variability indices consistent with sympathetic activation. Human cells showed accelerated repolarization only under catecholamine stress, indicating coolants may lower the threshold for triggered activity rather than cause resting arrhythmias.

Current U.S. flavor rules exempt menthol and synthetic coolants because they lack "characterizing flavor," allowing widespread use of WS-23 at concentrations often exceeding nicotine. This regulatory gap mirrors the menthol exception that sustained cigarette sales after other flavors were restricted. The mouse data align with earlier observational signals linking mentholated products to higher arrhythmia reports in emergency-department databases, yet no longitudinal human cohort has measured coolant biomarkers against incident atrial fibrillation or sudden cardiac arrest.

Next steps require controlled human exposure studies that track plasma coolant levels, heart-rate variability, and premature-beat frequency over months, plus FDA-mandated aerosol chemistry testing to quantify actual delivered doses. Without such data, policy remains anchored to preclinical signals whose translation to population-level cardiac risk is unknown.