title: Improved oxygenation by nitric oxide is enhanced by prior lung reaeration with surfactant, rather than positive end-expiratory pressure, in lung-lavaged rabbits.
abstract: OBJECTIVE
  The inhalation of nitric oxide increases oxygenation by improving the ventilation/perfusion ratios in neonates with respiratory distress syndrome and those ratios in adults with acute respiratory distress syndrome. There is evidence that inhaled nitric oxide is ineffective when the lung remains atelectatic and poorly inflated. This study aimed to enhance nitric oxide delivery by improving lung aeration by means of exogenous surfactant or by increasing positive end-expiratory pressure.
  
  
  METHODS
  Experimental, comparative study.
  
  
  METHODS
  Research laboratory of a large university.
  
  
  METHODS
  Twenty-eight adult New Zealand white rabbits, weighing 2.7 +/- 0.3 kg.
  
  
  METHODS
  Lung injury was induced by repeated whole-lung lavage with saline. The animals were mechanically ventilated with a tidal volume of 10 mL/kg, an FIO2 of 1.0, and a positive end-expiratory pressure of 6 cm H2O. Forty-five minutes after the last lavage, the animals were randomly assigned to five groups. In two groups, lung aeration was first increased either by instillation of a low dose of exogenous surfactant (25 mg/kg) or by increasing the positive end-expiratory pressure to 10 cm H2O, before inhalation of nitric oxide was started. In each of these animals, five different nitric oxide concentrations (4 to 20 parts per million) were inhaled for 30 mins, followed by a 30-min washout period. The other three groups served as controls and received only one treatment protocol: nitric oxide (4 to 20 parts per million), or surfactant (25 mg/kg), or positive end-expiratory pressure (10 cm H2O).
  
  
  RESULTS
  Before and after lavage, blood gases and lung mechanics were measured every 30 mins. Both strategies to increase lung aeration improved PaO2 values from 61 +/- 13 torr (8.1 +/- 1.7 kPa) to 200 to 300 torr (26.6 to 39.9 kPa) in 30 mins. After inhalation of nitric oxide, additional increases of oxygenation were seen only in the animals that received a low dose (25 mg/kg) of surfactant. The control group that inhaled nitric oxide showed no significant change in oxygenation, and four of the six animals did not survive the observation period. In the two groups in which positive end-expiratory pressure was increased to 10 cm H2O, half of the animals developed a pneumothorax during the observation period.
  
  
  CONCLUSIONS
  These data indicate that inhaled nitric oxide is able to improve arterial oxygenation after alveolar recruitment by means of a low dose of exogenous surfactant, and not by increase of positive end-expiratory pressure from 6 to 10 cm H2O, in lung-lavaged rabbits.
authors.affiliation: Department of Anesthesiology, Erasmus University Rotterdam, The Netherlands.
authors.forename: D
authors.initials: D
authors.lastname: Gommers
authors.forename: A
authors.initials: A
authors.lastname: Hartog
authors.forename: A
authors.initials: A
authors.lastname: van 't Veen
authors.forename: B
authors.initials: B
authors.lastname: Lachmann
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007231:Infant, Newborn; D009569:Nitric Oxide / Q000008:administration & dosage / Q000627:therapeutic use*; D011175:Positive-Pressure Respiration; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D011817:Rabbits; D012131:Respiratory Insufficiency / Q000188:drug therapy*; D013501:Surface-Active Agents / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D013501:Surface-Active Agents; D009569:Nitric Oxide