Watkinson W P, Campen M J, Nolan J P, Costa D L
Pulmonary Toxicology Branch, Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
Environ Health Perspect. 2001 Aug;109 Suppl 4(Suppl 4):539-46. doi: 10.1289/ehp.01109s4539.
Striking similarities have been observed in a number of extrapulmonary responses of rodents to seemingly disparate ambient pollutants. These responses are often characterized by primary decreases in important indices of cardiac and thermoregulatory function, along with secondary decreases in associated parameters. For example, when rats are exposed to typical experimental concentrations of ozone (O(3), they demonstrate robust and consistent decreases in heart rate (HR) ranging from 50 to 100 beats per minute, whereas core temperature (T(co) often falls 1.5-2.5 degrees C. Other related indices, such as metabolism, minute ventilation, blood pressure, and cardiac output, appear to exhibit similar deficits. The magnitudes of the observed decreases may be modulated by changes in experimental conditions and appear to vary inversely with both ambient temperature and body mass. More recent studies in which both healthy and compromised rats were exposed to either particulate matter or its specific components yielded similar results. The agents studied included representative examples of ambient, combustion, and natural source particles, along with individual or combined exposures to their primary metallic constituents. In addition to the substantial decreases in HR and T(co), similar to those seen with the O(3)-exposed rats, these animals also displayed numerous adverse changes in electrocardiographic waveforms and cardiac rhythm, frequently resulting in fatal outcomes. Although there is only limited experimental evidence that addresses the underlying mechanisms of these responses, there is some indication that they may be related to stimulation of pulmonary irritant receptors and that they may be at least partially mediated via the parasympathetic nervous system.
在啮齿动物对看似不同的环境污染物的许多肺外反应中，已观察到显著的相似性。这些反应的特征通常是心脏和体温调节功能的重要指标首先下降，以及相关参数的继发性下降。例如，当大鼠暴露于典型的实验浓度的臭氧（O₃）时，它们的心率（HR）会出现强劲且一致的下降，范围为每分钟50至100次，而核心体温（Tco）通常会下降1.5 - 2.5摄氏度。其他相关指标，如新陈代谢、分钟通气量、血压和心输出量，似乎也表现出类似的缺陷。观察到的下降幅度可能会受到实验条件变化的调节，并且似乎与环境温度和体重呈反比。最近对健康和受损大鼠暴露于颗粒物或其特定成分的研究也得出了类似的结果。所研究的物质包括环境、燃烧和天然来源颗粒的代表性例子，以及对其主要金属成分的单独或联合暴露。除了心率和核心体温大幅下降外，与暴露于臭氧的大鼠类似，这些动物的心电图波形和心律也出现了许多不良变化，常常导致致命后果。尽管仅有有限的实验证据涉及这些反应的潜在机制，但有迹象表明它们可能与肺刺激感受器的刺激有关，并且可能至少部分通过副交感神经系统介导。
