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, Ca2+ 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): 3.0±0.1   mg/m3, nicotine: 0.4±0.2 mg/m3, carbon monoxide: 12.4±1.6  ppm, or filtered air (FA) for 4, 8, or 12 wk (n=4–5/group]. Hearts were excised and Langendorff perfused for dual optical mapping with voltage- and Ca2+-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 Ca2+ alternans magnitude progressively increased in all groups. At 4 and 8 wk, there were no statistical differences in APD or Ca2+ alternans magnitude between SHS and FA groups. At 12 wk, both APD and Ca2+ alternans magnitude were significantly increased in the SHS compared to FA group (p<0.05). SHS exposure did not impact the time constant of Ca2+ transient decay (τ) at any exposure time point. At 12 wk exposure, the recovery of Ca2+ transient amplitude with premature stimuli was slightly (but nonsignificantly) delayed in SHS compared to FA hearts, suggesting that Ca2+ 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