Effect of altered dose rate on NO2 uptake and transformation in isolated lungs.
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.
Postlethwait
E M
EM
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77550.
Mustafa
M G
MG
D000818:Animals; D001711:Biotransformation; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism*; D008297:Male; D009585:Nitrogen Dioxide / Q000493:pharmacokinetics*; D010126:Ozone / Q000493:pharmacokinetics; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D010126:Ozone; D009585:Nitrogen Dioxide