Lung Diffusing Capacities ( D L ) for Nitric Oxide (NO) and Carbon Monoxide (CO): The Evolving Story

Abstract Nitric oxide and carbon monoxide diffusing capacities ( D LNO and D LCO ) obey Fick's First Law of Diffusion and the basic principles of chemical kinetic theory. NO gas transfer is dominated by membrane diffusion ( D M ), whereas CO transfer is limited by diffusion plus chemical reaction within the red cell. Marie Krogh, who pioneered the single‐breath measurement of D LCO in 1915, believed that the combination of CO with red cell hemoglobin (Hb) was instantaneous. Roughton and colleagues subsequently showed, in vitro , that the reaction rate was finite, and prolonged in the presence of high . Roughton and Forster (R‐F) proposed that the resistance to transfer (1/ D L ) was the sum of the membrane resistance (1/ D M ) and (1/ θV c), the red cell resistance ( θ being the CO or NO conductance for blood uptake and V c the capillary volume). From this R‐F equation, D M for CO and V c can be solved with simultaneous NO and CO inhalation. At near maximum exercise, D MCO and V c for normal subjects were 88% and 79%, respectively, of morphometric values. The validity of these calculations depends on the values chosen for θ for CO and NO, and on the diffusivity of NO versus CO. Recent mathematical modeling suggests that θ for NO is “effectively” infinite because NO reacts only with Hb in the outer 0.1 μM of the red cell. An “infinite θ NO ” recalculation reduced D MCO to 53% and increased V c to 95% of morphometric values. © 2020 American Physiological Society. Compr Physiol 10:73‐97, 2020.