Environmental Public Health Division, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
Environ Health Perspect. 2011 Jul;119(7):951-7. doi: 10.1289/ehp.1003200. Epub 2011 Mar 4.
Diesel exhaust (DE), which is emitted from on- and off-road sources, is a complex mixture of toxic gaseous and particulate components that leads to triggered adverse cardiovascular effects such as arrhythmias.
We hypothesized that increased risk of triggered arrhythmias 1 day after DE exposure is mediated by airway sensory nerves bearing transient receptor potential (TRP) channels [e.g., transient receptor potential cation channel, member A1 (TRPA1)] that, when activated by noxious chemicals, can cause a centrally mediated autonomic imbalance and heightened risk of arrhythmia.
Spontaneously hypertensive rats implanted with radiotelemeters were whole-body exposed to either 500 μg/m³ (high) or 150 μg/m³ (low) whole DE (wDE) or filtered DE (fDE), or to filtered air (controls), for 4 hr. Arrhythmogenesis was assessed 24 hr later by continuous intravenous infusion of aconitine, an arrhythmogenic drug, while heart rate (HR) and electrocardiogram (ECG) were monitored.
Rats exposed to wDE or fDE had slightly higher HRs and increased low-frequency:high-frequency ratios (sympathetic modulation) than did controls; ECG showed prolonged ventricular depolarization and shortened repolarization periods. Rats exposed to wDE developed arrhythmia at lower doses of aconitine than did controls; the dose was even lower in rats exposed to fDE. Pretreatment of low wDE-exposed rats with a TRPA1 antagonist or sympathetic blockade prevented the heightened sensitivity to arrhythmia.
These findings suggest that a single exposure to DE increases the sensitivity of the heart to triggered arrhythmias. The gaseous components appear to play an important role in the proarrhythmic response, which may be mediated by activation of TRPA1, and subsequent sympathetic modulation. As such, toxic inhalants may partly exhibit their toxicity by lowering the threshold for secondary triggers, complicating assessment of their risk.
柴油废气（DE）来自道路和非道路源，是一种复杂的有毒气体和颗粒成分混合物，会导致心律失常等触发的不良心血管效应。
我们假设，接触 DE 后 1 天，触发心律失常的风险增加是由气道感觉神经介导的，这些神经携带瞬时受体电位（TRP）通道[例如，瞬时受体电位阳离子通道，成员 A1（TRPA1）]，当这些通道被有害化学物质激活时，会导致中枢介导的自主神经失衡和心律失常风险增加。
植入无线电遥测仪的自发性高血压大鼠接受全身暴露于 500μg/m³（高）或 150μg/m³（低）全 DE（wDE）或过滤 DE（fDE）或过滤空气（对照）4 小时。24 小时后，通过连续静脉输注乌头碱评估心律失常发生情况，乌头碱是一种致心律失常药物，同时监测心率（HR）和心电图（ECG）。
与对照组相比，暴露于 wDE 或 fDE 的大鼠 HR 略高，低频：高频比值（交感神经调节）增加；心电图显示心室去极化延长和复极化期缩短。与对照组相比，暴露于 wDE 的大鼠在较低剂量的乌头碱下发生心律失常；暴露于 fDE 的大鼠剂量甚至更低。用 TRPA1 拮抗剂或交感神经阻断预处理低剂量 wDE 暴露的大鼠可防止心律失常敏感性增加。
这些发现表明，单次接触 DE 会增加心脏对触发心律失常的敏感性。气态成分似乎在致心律失常反应中起重要作用，该反应可能是通过激活 TRPA1 和随后的交感神经调节介导的。因此，有毒吸入剂可能通过降低二次触发的阈值部分表现出其毒性，从而使对其风险的评估变得复杂。
