Reactive uptake governs the pulmonary air space removal of inhaled nitrogen dioxide

With the use of an isolated rat lung model, we investigated pulmonary air space absorption kinetics of the reactive gas NO2 in an effort to determine the contributory role of chemical reaction(s) vs. physical solubility. Unperfused lungs were employed, because vascular perfusion had no effect on acute (0- to 60-min) NO2 absorption rates. We additionally found the following: 1) Uptake was proportional to exposure rates (2-14 micrograms NO2/min; 10-63 ppm; 37 degrees C) but saturated with exposures greater than or equal to 14 micrograms NO2/min. 2) Uptake was temperature (22-48 degrees C) dependent but, regardless of temperature, attained apparent saturation at 10.6 micrograms NO2/min. 3) Lung surface area (SA) was altered by increasing functional residual capacity (FRC). Expanded SA (8 ml FRC) and temperature (48 degrees C) both raised fractional uptakes (greater than or equal to 0.81) relative to 4 ml FRC, 37 degrees C (0.67). Uptake rates normalized per unit estimated SA revealed no independent effect of FRC on fractional uptake. However, temperature produced a profound effect (48 degrees C = 0.93; 4 and 8 ml FRC = 0.54). 4) Arrhenius plots (ln k' vs. 1/T), which utilized derived reactive uptake coefficients (k'), showed linearity (r2 = 0.94) and yielded an activation energy of 7,536 kcal.g-1.mol-1 and Q10 of 1.43, all consistent with a reaction-mediated process. These findings, particularly the effects of temperature, suggest that acute NO2 uptake in pulmonary air spaces is, in part, rate limited by chemical reaction of NO2 with epithelial surface constituents rather than by direct physical solubility.