Significant blood resistance to nitric oxide transfer in the lung.
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.
Department of Medicine, Hinchingbrooke Hospital, Huntingdon PE29 6NT, UK. colin.borland@hinchingbrooke.nhs.uk
Colin D R
CD
Borland
Helen
H
Dunningham
Fiona
F
Bottrill
Alain
A
Vuylsteke
Cuneyt
C
Yilmaz
D Merrill
DM
Dane
Connie C W
CC
Hsia
D000818:Animals; D001802:Blood Substitutes / Q000494:pharmacology; D001810:Blood Volume; D002199:Capillary Permeability / Q000187:drug effects; D002248:Carbon Monoxide / Q000097:blood; D002463:Cell Membrane Permeability / Q000187:drug effects; D004285:Dogs; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D005078:Exchange Transfusion, Whole Blood; D006454:Hemoglobins / Q000494:pharmacology; D006461:Hemolysis; D008168:Lung / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008955:Models, Cardiovascular; D009569:Nitric Oxide / Q000097:blood*; D011652:Pulmonary Circulation; D011653:Pulmonary Diffusing Capacity / Q000187:drug effects; D013997:Time Factors
D001802:Blood Substitutes; D006454:Hemoglobins; C402601:hemoglobin glutamer-200; D009569:Nitric Oxide; D002248:Carbon Monoxide