title: The significant blood resistance to lung nitric oxide transfer lies within the red cell.
abstract: The lung nitric oxide (NO) diffusing capacity (DlNO) mainly reflects alveolar-capillary membrane conductance (Dm). However, blood resistance has been shown in vitro and in vivo. To explore whether this resistance lies in the plasma, the red blood cell (RBC) membrane, or in the RBC interior, we measured the NO diffusing capacity (Dno) in a membrane oxygenator circuit containing ∼1 liter of horse or human blood exposed to 14 parts per million NO under physiological conditions on 7 separate days. We compared results across a 1,000-fold change in extracellular diffusivity using dextrans, plasma, and physiological salt solution. We halved RBC surface area by comparing horse and human RBCs. We altered the diffusive resistance of the RBC interior by adding sodium nitrite converting oxyhemoglobin to methemoglobin. Neither increased viscosity nor reduced RBC size reduced Dno. Adding sodium nitrite increased methemoglobin and was associated with a steady fall in Dno (P < 0.001). Similar results were obtained at NO concentrations found in vivo. The RBC interior appears to be the site of the blood resistance.
authors.affiliation: Department of Anaesthetic Research, Papworth Hospital, Cambridgeshire, United Kingdom.
authors.forename: Colin
authors.initials: C
authors.lastname: Borland
authors.forename: Fiona
authors.initials: F
authors.lastname: Bottrill
authors.forename: Aled
authors.initials: A
authors.lastname: Jones
authors.forename: Chris
authors.initials: C
authors.lastname: Sparkes
authors.forename: Alain
authors.initials: A
authors.lastname: Vuylsteke
mesh_terms: D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D008706:Methemoglobin / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D010108:Oxyhemoglobins / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000098:blood supply* / Q000378:metabolism; D011653:Pulmonary Diffusing Capacity / Q000502:physiology; D012977:Sodium Nitrite / Q000378:metabolism
chemical_list: D010108:Oxyhemoglobins; D009569:Nitric Oxide; D008706:Methemoglobin; D012977:Sodium Nitrite; D010100:Oxygen
keywords: diffusing capacity for carbon monoxide; diffusing capacity for oxygen; lung diffusing capacity for nitric oxide; membrane oxygenator