PULMONARY DIFFUSING CAPACITIES FOR NITRIC-OXIDE AND CARBON-MONOXIDE DETERMINED BY REBREATHING IN DOGS

Pulmonary diffusing capacities (DL) of NO and CO were determined simultaneously from rebreathing equilibration kinetics in anesthetized paralyzed supine dogs (mean body wt 20 kg) after denitrogenation (replacement of N2 by Ar). During rebreathing the dogs were ventilated in closed circuit with a gas mixture containing 0.06% NO, 0.06% 13C18O, and 1% He in Ar for 15 s, with tidal volume of 0.5 liter and frequency of 60/min. The partial pressures of NO, 13C18O, 16O18O, N2, Ar, CO2, and He in the trachea were continuously analyzed by mass spectrometry. Measurements were performed at various O2 levels characterized by the mean end-expired PO2 during rebreathing (P̄E(O2)'). In control conditions ('normoxia', P̄E(O2)' = 67 ± 8 Torr) the following mean ± SD values were obtained (in ml · min-1 · Torr-1): DL(NO) = 52.4 ± 11.0 and DL(CO) = 15.4 ± 2.9. In hypoxia (P̄E(O2)' = 24 ± 7 Torr) DL(NO) increased by 11 ± 8% and DL(CO) by 19 ± 10%, and in hyperoxia (P̄E(O2)' = 390 ± 26 Torr) DL(NO) decreased to 87 ± 3% and DL(CO) to 56 ± 8% with respect to values in normoxia. DL(NO)/DL(CO) or 3.24 ± 0.06 (hypoxia), 3.38 ± 0.31 (normoxia), and 5.54 ± 1.04 (hyperoxia) were significantly higher than the NO/CO Krogh diffusion constant ratio (1.92) predicted for simple diffusion through aqueous layers. With increasing O2 uptake elicited by 2,4-dinitrophenol, DL(NO) and DL(CO) increased and DL(NO)/DL(CO) remained close to unchanged. The results suggest that the combined effects of diffusion and chemical reaction with hemoglobin limit alveolar-capillary transport of CO. If it is assumed that reaction kinetics of NO with hemoglobin (known to be extremely fast) are not rate limiting for NO uptake, the contribution of the slow chemical reaction with hemoglobin to the total CO uptake resistance (=1/DL(CO)) was estimated to be 38% in hypoxia, 41% in normoxia, and 64% in hyperoxia. The various factors expected to restrict the validity of this analysis are discussed, in particular the effects of functional inhomogeneity.