Department of Pharmacology, University of California, Davis, Davis, California, USA.
Center for Health and the Environment, University of California, Davis, Davis, California, USA.
Environ Health Perspect. 2018 Dec;126(12):127001. doi: 10.1289/EHP3664.
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.
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): [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.
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.
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.
流行病学证据表明,大多数归因于二手烟(SHS)暴露的死亡与心血管相关。然而,据我们所知,SHS 对心脏电生理学、[Formula: see text] 处理和心律失常风险的影响尚未得到研究。
本研究旨在调查环境相关浓度的 SHS 对心脏电生理学和心律失常指标的影响。
雄性 C57BL/6 小鼠暴露于 SHS[总悬浮颗粒物(THS):[Formula: see text]、尼古丁:[Formula: see text]、一氧化碳:[Formula: see text]或过滤空气(FA)4、8 或 12 周([Formula: see text])。取出心脏,Langendorff 灌流,用电压和[Formula: see text]敏感染料进行双光学映射。
在缓慢起搏率下,SHS 暴露不会改变基线电生理参数。随着起搏频率的增加,动作电位时程(APD)和细胞内[Formula: see text]交替幅度在所有组中逐渐增加。在 4 和 8 周时,SHS 和 FA 组之间的 APD 或[Formula: see text]交替幅度没有统计学差异。在 12 周时,与 FA 组相比,SHS 组的 APD 和[Formula: see text]交替幅度均显著增加([Formula: see text])。SHS 暴露在任何暴露时间点均不影响[Formula: see text]瞬变衰减的时间常数([Formula: see text])。在 12 周暴露时,与 FA 心脏相比,SHS 心脏的早期刺激的[Formula: see text]瞬变幅度恢复稍有(但无统计学意义)延迟,表明通过兰尼碱受体的[Formula: see text]释放可能受损。
在雄性小鼠中,慢性暴露于与人社交情况下相关水平的 SHS 增加了其对心脏交替的易感性,这是室性心律失常的已知前兆。https://doi.org/10.1289/EHP3664.