Environmental Public Health Division, U.S. Environmental Protection Agency, 109 Alexander Drive, B143-01, Research Triangle Park, NC 27711, USA.
Toxicol Sci. 2009 Dec;112(2):532-42. doi: 10.1093/toxsci/kfp214. Epub 2009 Sep 11.
Epidemiological studies demonstrate an association between arrhythmias and air pollution. Aconitine-induced cardiac arrhythmia is widely used experimentally to examine factors that alter the risk of arrhythmogenesis. In this study, Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rats acutely exposed to synthetic residual oil fly ash (s-ROFA) particles (450 mug/m(3)) were "challenged" with aconitine to examine whether a single exposure could predispose to arrhythmogenesis. Separately, SH rats were exposed to varied particulate matter (PM) concentrations (0.45, 1.0, or 3.5 mg/m(3) s-ROFA), or the irritant gas acrolein (3 ppm), to better assess the generalization of this challenge response. Rather than directly cause arrhythmias, we hypothesized that inhaled air pollutants sensitize the heart to subsequent dysrhythmic stimuli. Twenty-four hour postexposure, urethane-anesthetized rats were monitored for heart rate (HR), electrocardiogram, and blood pressure (BP). SH rats had higher baseline HR and BP and significantly longer PR intervals, QRS duration, QTc, and JTc than WKY rats. PM exposure caused a significant increase in the PR interval, QRS duration, and QTc in WKY rats but not in SH rats. Heart rate variability was significantly decreased in WKY rats after PM exposure but increased in SH rats. Cumulative dose of aconitine that triggered arrhythmias in air-exposed SH rats was lower than WKY rats and even lower for each strain postexposure. SH rats exposed to varied concentrations of PM or acrolein developed arrhythmia at significantly lower doses of aconitine than controls; however, there was no PM concentration-dependent response. In conclusion, a single exposure to air pollution may increase the sensitivity of cardiac electrical conduction to disruption. Moreover, there seem to be host factors (e.g., cardiovascular disease) that increase vulnerability to triggered arrhythmias regardless of the pollutant or its concentration.
流行病学研究表明心律失常与空气污染之间存在关联。乌头碱诱导的心律失常广泛用于实验研究，以检查改变心律失常发生风险的因素。在这项研究中，急性暴露于合成残余油飞灰（s-ROFA）颗粒（450 µg/m3）的 Wistar-Kyoto（WKY）和自发性高血压（SH）大鼠接受乌头碱“挑战”，以检查单次暴露是否会导致心律失常易感性增加。此外，SH 大鼠还暴露于不同的颗粒物（PM）浓度（0.45、1.0 或 3.5 mg/m3 s-ROFA）或刺激性气体丙烯醛（3 ppm），以更好地评估这种挑战反应的普遍性。我们假设，吸入的空气污染物不会直接引起心律失常，而是使心脏对随后的心律失常刺激敏感。暴露后 24 小时，对麻醉的大鼠进行心率（HR）、心电图和血压（BP）监测。SH 大鼠的基础心率和血压较高，PR 间期、QRS 持续时间、QTc 和 JTc 明显长于 WKY 大鼠。PM 暴露使 WKY 大鼠的 PR 间期、QRS 持续时间和 QTc 显著增加，但对 SH 大鼠无影响。PM 暴露后，WKY 大鼠的心率变异性显著降低，而 SH 大鼠的心率变异性增加。在空气暴露的 SH 大鼠中触发心律失常的乌头碱累积剂量低于 WKY 大鼠，并且暴露后每个品系的剂量甚至更低。暴露于不同浓度的 PM 或丙烯醛的 SH 大鼠在接受乌头碱的剂量明显低于对照的情况下发生心律失常，但没有 PM 浓度依赖性反应。总之，单次暴露于空气污染可能会增加心脏电传导中断的敏感性。此外，似乎存在宿主因素（例如心血管疾病），无论污染物或其浓度如何，都会增加对触发心律失常的易感性。
