Significant blood resistance to nitric oxide transfer in the lung

Abstract

Lung diffusing capacity for nitric oxide (DLNO) is used to measure alveolar membrane conductance (DMNO), but disagreement remains as to whether DMNO=DLNO, and whether blood conductance (thetaNO)=infinity. Our previous in vitro and in vivo studies suggested that thetaNO<infinity. 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 DNO to DCO by 12% (all P<0.001). In three anesthetized dogs, DLNO and DLCO 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, DLNO/DLCO=4.5. After exchange transfusion, DLNO rose 57+/-16% (mean+/-SD, P=0.02) and DLNO/DLCO=7.1, whereas DLCO remained unchanged. Thus, in vitro and in vivo data directly demonstrate a finite thetaNO. We conclude that the erythrocyte and/or its immediate environment imposes considerable resistance to alveolar-capillary NO uptake. DLNO 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 thetaNO [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 thetaNO=4.5 ml NO.(min.Torr.ml blood)(-1) for calculation of DM(NO) and pulmonary capillary blood volume from DLNO and DLCO.

Fig. 1.

In vitro diffusing capacity for nitric oxide (Dno) and carbon monoxide (Dco) measured in the membrane oxygenator model after successive addition of free Hb or bovine Hb glutamer-200 (Oxyglobin) solution. Values are means ± SD of 3 replicate runs.

Fig. 2.

In vitro Dno and Dco measured in the membrane oxygenator model with successive addition of bovine Hb glutamer-200 (Oxyglobin) solution followed by water hemolysis. Individual runs are shown.

Fig. 3.

Blood parameters before and after successive in vivo exchange transfusion with Oxyglobin solution. Values are means ± SD. *P < 0.05 vs. baseline.

Fig. 4.

In vivo lung diffusing capacity for NO (Dl_NO) in individual animals (closed symbols, dashed lines) rose significantly after successive exchange transfusion with Oxyglobin solution compared with baseline (P < 0.05 by repeated-measures ANOVA), while DL_CO in each animal (open symbols, solid lines) remained unchanged.

Fig. 5.

Membrane diffusing capacity for CO (Dm_CO) and pulmonary capillary blood volume (Vc) estimated by the Roughton-Forster method (method 1), the NO-CO method with the assumption that specific transfer conductance of blood per milliliter for NO (θ_NO) = ∞ (method 2), and the NO-CO method with the assumption that θ_NO = 4.5 ml NO·(ml blood·min·Torr)⁻¹. Values are means ± SD. Estimates by all 3 methods were significantly different from one another by repeated-measures ANOVA (all P < 0.05).