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



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+Ca2+ handling, and arrhythmia risk has not been studied.


The purpose of this study was to investigate the impact of an environmentally relevant concentration of SHS on cardiac electrophysiology and indicators of arrhythmia.


Male C57BL/6 mice were exposed to SHS [total suspended particles (THS): 3.0±0.1  mg/m33.0±0.1  mg/m3, nicotine: 0.4±0.2 mg/m30.4±0.2 mg/m3, carbon monoxide: 12.4±1.6 ppm12.4±1.6 ppm, or filtered air (FA) for 4, 8, or 12 wk (n=4–5/groupn=4–5/group]. Hearts were excised and Langendorff perfused for dual optical mapping with voltage- and Ca2+Ca2+-sensitive dyes.


At slow pacing rates, SHS exposure did not alter baseline electrophysiological parameters. With increasing pacing frequency, action potential duration (APD), and intracellular Ca2+Ca2+ alternans magnitude progressively increased in all groups. At 4 and 8 wk, there were no statistical differences in APD or Ca2+Ca2+ alternans magnitude between SHS and FA groups. At 12 wk, both APD and Ca2+Ca2+ alternans magnitude were significantly increased in the SHS compared to FA group (p<0.05p<0.05). SHS exposure did not impact the time constant of Ca2+Ca2+ transient decay (ττ) at any exposure time point. At 12 wk exposure, the recovery of Ca2+Ca2+ transient amplitude with premature stimuli was slightly (but nonsignificantly) delayed in SHS compared to FA hearts, suggesting that Ca2+Ca2+ release via ryanodine receptors may be impaired.


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

Wang, Z., Wang, L., Tapa, S., Pinkerton, K. E., Chen, C. Y., & Ripplinger, C. M. (2018). Exposure to Secondhand Smoke and Arrhythmogenic Cardiac Alternans in a Mouse Model. Environmental Health Perspectives, 126(12), 127001.
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United States