Effects of L-NAME and inhaled nitric oxide on ventilator-induced lung injury in isolated, perfused rabbit lungs

Crit Care Med. 2004 Sep;32(9):1872-8. doi: 10.1097/01.ccm.0000139605.38527.1b.


Objective: To determine whether nitric oxide (NO) might modulate ventilator-induced lung injury.

Design: Randomized prospective animal study.

Setting: Animal research laboratory in a university hospital.

Subjects: Isolated, perfused rabbit heart-lung preparation.

Interventions: 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).

Measurements and main 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.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Animals
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use*
  • NG-Nitroarginine Methyl Ester / pharmacology
  • NG-Nitroarginine Methyl Ester / therapeutic use*
  • Nitric Oxide / pharmacology
  • Nitric Oxide / therapeutic use*
  • Oxidative Stress / drug effects
  • Prospective Studies
  • Rabbits
  • Random Allocation
  • Respiration, Artificial / adverse effects*
  • Respiratory Distress Syndrome / etiology
  • Respiratory Distress Syndrome / physiopathology
  • Respiratory Distress Syndrome / prevention & control*
  • Statistics, Nonparametric
  • Stress, Mechanical
  • Vasodilator Agents / pharmacology
  • Vasodilator Agents / therapeutic use*


  • Enzyme Inhibitors
  • Vasodilator Agents
  • Nitric Oxide
  • NG-Nitroarginine Methyl Ester