Exposure to Secondhand Smoke and Arrhythmogenic Cardiac Alternans in a Mouse Model

BACKGROUND: Epidemiological evidence suggests that a majority of deaths attributed to secondhand smoke (SHS) exposure are cardiovascular related. However, to our knowledge, the impact of SHS on cardiac electrophysiology, [Formula: see text] handling, and arrhythmia risk has not been studied. OBJECTIVES: The purpose of this study was to investigate the impact of an environmentally relevant concentration of SHS on cardiac electrophysiology and indicators of arrhythmia. METHODS: Male C57BL/6 mice were exposed to SHS [total suspended particles (THS): [Formula: see text] , nicotine: [Formula: see text] , carbon monoxide: [Formula: see text] , or filtered air (FA) for 4, 8, or 12 wk ([Formula: see text]]. Hearts were excised and Langendorff perfused for dual optical mapping with voltage- and [Formula: see text]-sensitive dyes. RESULTS: At slow pacing rates, SHS exposure did not alter baseline electrophysiological parameters. With increasing pacing frequency, action potential duration (APD), and intracellular [Formula: see text] alternans magnitude progressively increased in all groups. At 4 and 8 wk, there were no statistical differences in APD or [Formula: see text] alternans magnitude between SHS and FA groups. At 12 wk, both APD and [Formula: see text] alternans magnitude were significantly increased in the SHS compared to FA group ([Formula: see text]). SHS exposure did not impact the time constant of [Formula: see text] transient decay ([Formula: see text]) at any exposure time point. At 12 wk exposure, the recovery of [Formula: see text] transient amplitude with premature stimuli was slightly (but nonsignificantly) delayed in SHS compared to FA hearts, suggesting that [Formula: see text] release via ryanodine receptors may be impaired. CONCLUSIONS: In male mice, chronic exposure to SHS at levels relevant to social situations in humans increased their susceptibility to cardiac alternans, a known precursor to ventricular arrhythmia. https://doi.org/10.1289/EHP3664