title: Effects of L-NAME and inhaled nitric oxide on ventilator-induced lung injury in isolated, perfused rabbit lungs.
abstract: OBJECTIVE
  To determine whether nitric oxide (NO) might modulate ventilator-induced lung injury.
  
  
  METHODS
  Randomized prospective animal study.
  
  
  METHODS
  Animal research laboratory in a university hospital.
  
  
  METHODS
  Isolated, perfused rabbit heart-lung preparation.
  
  
  METHODS
  Thirty-six isolated, perfused rabbit lungs were randomized into six groups (n = 6) and ventilated using pressure-controlled ventilation for two consecutive periods (T1 and T2). Peak alveolar pressure during pressure-controlled ventilation was 20 cm H2O at T1 and was subsequently (T2) either reduced to 15 cm H2O in the three low-pressure control groups (Cx) or increased to 25 cm H2O in the three high-pressure groups (Px). In the control and high-pressure groups, NO concentration was increased to approximately equal to 20 ppm (inhaled NO groups: CNO, PNO), reduced by NO synthase inhibition (L-NAME groups: CL-Name, PL-Name), or not manipulated (groups CE, PE).
  
  
  RESULTS
  Changes in ultrafiltration coefficients (deltaKf [vascular permeability index: g.min(-1).cm H2O(-1).100 g(-1)]), bronchoalveolar lavage fluid 8-isoprostane, and NOx (nitrate + nitrite) concentrations were the measures examined. Neither L-NAME nor inhaled NO altered lung permeability in the setting of low peak alveolar pressure (control groups). In contrast, L-NAME virtually abolished the change in permeability (deltaKf: PL-Name (0.10 +/- 0.03) vs. PNO [1.75 +/- 1.10] and PE [0.37 +/- 0.11; p <.05]) and the increase in bronchoalveolar lavage 8-isoprostane concentration induced by high-pressure ventilation. Although inhaled NO was associated with the largest change in permeability, no significant difference between the PE and PL-NAME groups was observed. The change in permeability (deltaKf) correlated with bronchoalveolar lavage NOx (r2 =.6; p <.001).
  
  
  CONCLUSIONS
  L-NAME may attenuate ventilator-induced microvascular leak and lipid peroxidation and NO may contribute to the development of ventilator-induced lung injury. Measurement of NO metabolites in the bronchoalveolar lavage may afford a means to monitor lung injury induced by mechanical stress.
authors.affiliation: University of Minnesota, Pulmonary and Critical Care Division, Regions Hospital, St. Paul, MN, USA.
authors.forename: Alain F
authors.initials: AF
authors.lastname: Broccard
authors.forename: François
authors.initials: F
authors.lastname: Feihl
authors.forename: Christine
authors.initials: C
authors.lastname: Vannay
authors.forename: Michele
authors.initials: M
authors.lastname: Markert
authors.forename: John
authors.initials: J
authors.lastname: Hotchkiss
authors.forename: Marie-Denise
authors.initials: MD
authors.lastname: Schaller
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D011446:Prospective Studies; D011817:Rabbits; D011897:Random Allocation; D012121:Respiration, Artificial / Q000009:adverse effects*; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D018709:Statistics, Nonparametric; D013314:Stress, Mechanical; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester