title: Pulmonary NO synthase inhibition and inspired CO2: effects on V'/Q' and pulmonary blood flow distribution.
abstract: Inhaled carbon dioxide decreases ventilation/perfusion ratio (V'/Q') heterogeneity in dogs. The aim of this study was to test whether inhaled CO2 improves the V'/Q' by inhibition of nitric oxide production and whether inhibition of endogenous NO production in the lung alters gas exchange and V'/Q' matching. Eleven healthy dogs were anaesthetized and mechanically ventilated. The multiple inert gas elimination technique (MIGET) was used to measure V'/Q' heterogeneity and regional pulmonary blood flow heterogeneity was assessed in five dogs using fluorescent microspheres. In a separate set of five dogs, exhaled NO levels were measured via chemiluminescence. All dogs were studied before and after 4.8% inspired CO2, and then given the NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME, 10 mg x kg(-1)) via nebulization, after which they were studied again with room air and inhaled CO2. CO2 and L-NAME improved arterial and alveolar oxygen tension, but the improvements with L-NAME did not reach statistical significance. Improved V'/Q' matching, as assessed by the MIGET, occurred under all experimental conditions. Exhaled NO levels were reduced by 40% with CO2 and 70% with L-NAME. The standard deviation of regional pulmonary blood flow assessed via microspheres decreased only with inhaled CO2. Fractal analysis of pulmonary blood flow distributions revealed that regional blood flow was highly correlated with flow to neighbouring pieces of lung in all four conditions with no changes in the fractal dimension. Inspired carbon dioxide improves ventilation perfusion ratio matching and is associated with a more homogeneous distribution of pulmonary blood flow. Although inspired carbon dioxide causes a reduction in exhaled nitric oxide, the differences in pulmonary perfusion distributions found between carbon dioxide and N(omega)-nitro-L-arginine methyl ester suggest that the carbon dioxide effect is not mediated by a reduction in nitric oxide production. The improved ventilation perfusion ratio matching with inhibition of nitric oxide synthase suggests the intriguing possibility requiring further study that endogenous production of nitric oxide in the lung does not subserve ventilation perfusion ratio regulation.
authors.affiliation: Dept of Paediatrics, Children's Hospital and Medical Centre, Seattle, WA 98105-0371, USA.
authors.forename: T V
authors.initials: TV
authors.lastname: Brogan
authors.forename: R G
authors.initials: RG
authors.lastname: Hedges
authors.forename: S
authors.initials: S
authors.lastname: McKinney
authors.forename: H T
authors.initials: HT
authors.lastname: Robertson
authors.forename: M P
authors.initials: MP
authors.lastname: Hlastala
authors.forename: E R
authors.initials: ER
authors.lastname: Swenson
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D002245:Carbon Dioxide / Q000008:administration & dosage* / Q000494:pharmacology; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D008168:Lung / Q000201:enzymology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D011652:Pulmonary Circulation / Q000187:drug effects; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D014692:Ventilation-Perfusion Ratio / Q000187:drug effects*
chemical_list: D004791:Enzyme Inhibitors; D002245:Carbon Dioxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester