Postlethwait E M, Mustafa M G
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77550.
J Toxicol Environ Health. 1989;26(4):497-507. doi: 10.1080/15287398909531272.
While the pulmonary toxicity of NO2 is clearly established, the mechanism by which it is removed from inspired air is poorly understood. Uptake is most likely dependent on chemical reaction since, despite limited per se gaseous NO2 aqueous solubility, uptake proceeds rapidly without ready saturation. We utilized an isolated perfused rat lung model to characterize the effect of dose rate on uptake and transformation. Dose rate was varied via alterations in inspired concentration, tidal volume, and ventilation frequency. Dose equaled the total amount inhaled, uptake the amount removed from inspired air, and transformation the amount of NO2- that accumulated in the perfusate. We found a linear proportionality between both inspired concentration (4-20 ppm) and minute ventilation (45-130 ml/min) and uptake. Fractional uptakes (65%) were similar for all groups. Regression of combined concentration and minute ventilation data yielded a linear relationship between total inspired dose (25-330 micrograms NO2) and both uptake (r2 = 0.99) and transformation (r2 = 0.98). Testing of the functional descriptions resulted in measured uptakes and transformation that fell within a few percentage points of those predicted. We conclude that in acutely exposed isolated lungs (1) NO2 uptake is dependent on total inhaled dose rather than on the variables which serve to affect dose rate, (2) transformation is related to both total inspired dose and uptake, and (3) uptake is more accurately described using a regression equation rather than by use of fractional uptakes.
虽然二氧化氮的肺毒性已明确确定，但其从吸入空气中清除的机制却知之甚少。摄取很可能依赖于化学反应，因为尽管二氧化氮本身的气态水溶性有限，但摄取过程迅速且不易饱和。我们利用离体灌注大鼠肺模型来表征剂量率对摄取和转化的影响。通过改变吸入浓度、潮气量和通气频率来改变剂量率。剂量等于吸入的总量，摄取量是从吸入空气中清除的量，转化量是灌注液中积累的亚硝酸根离子的量。我们发现吸入浓度（4 - 20 ppm）和分钟通气量（45 - 130 ml/min）与摄取量之间均呈线性比例关系。所有组的分数摄取率（65%）相似。综合浓度和分钟通气量数据的回归分析得出，总吸入剂量（25 - 330微克二氧化氮）与摄取量（r2 = 0.99）和转化量（r2 = 0.98）之间均呈线性关系。对功能描述的测试结果表明实测的摄取量和转化量与预测值相差几个百分点。我们得出结论，在急性暴露离体肺中：（1）二氧化氮摄取量取决于总吸入剂量而非影响剂量率的变量；（2）转化与总吸入剂量和摄取量均相关；（3）使用回归方程而非分数摄取率能更准确地描述摄取量。
