Significant blood resistance to nitric oxide transfer in the lung

Lung diffusing capacity for nitric oxide (DL_NO) is used to measure alveolar membrane conductance (DM_NO), but disagreement remains as to whether DM_NO= DL_NO, and whether blood conductance (θ_NO) = ∞. Our previous in vitro and in vivo studies suggested that θ_NO < ∞. We now show in a membrane oxygenator model perfused with whole blood that addition of a cell-free bovine hemoglobin (Hb) glutamer-200 solution increased diffusing capacity of the circuit (D) for NO (DNO) by 39%, D for carbon monoxide (Dco) by 24%, and the ratio of DL_NO to Dco by 12% (all P < 0.001). In three anesthetized dogs, DL_NO and DL_CO were measured by a rebreathing technique before and after three successive equal volume-exchange transfusions with bovine Hb glutamer-200 (10 ml/kg each, total exchange 30 ml/kg). At baseline, DL_NO/DL_CO= 4.5. After exchange transfusion, DL_NO rose 57 ± 16% (mean ± SD, P = 0.02) and DL_NO/DL_CO = 7.1, whereas DL_CO remained unchanged. Thus, in vitro and in vivo data directly demonstrate a finite θ_NO. We conclude that the erythrocyte and/or its immediate environment imposes considerable resistance to alveolar-capillary NO uptake. DL_NO is sensitive to dynamic hematological factors and is not a pure index of conductance of the alveolar tissue membrane. With successive exchange transfusion, the estimated in vivo θ_NO [5.1 ml NO·(ml blood·min·Torr)^-1] approached 4.5 ml NO·(ml blood·min·Torr)^-1, which was derived from in vitro measurements by Carlsen and Comroe (J Gen Physiol 42: 83-107, 1958). Therefore, we suggest use of θ_No = 4.5 ml NO·(min· Torr·ml blood)^-1 for calculation of DM_NO and pulmonary capillary blood volume from DL_NO and DL_CO