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

Alain F. Broccard, François Feihl, Christine Vannay, Michele Markert, John Hotchkiss, Marie Denise Schaller

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27 Scopus citations


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-sis 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 H 2O in the three low-pressure control groups (Cx) or increased to 25 cm H2O in the three high-pressure groups (P x). In the control and high-pressure groups, NO concentration was increased to ≅20 ppm (inhaled NO groups: CNO, PNO), reduced by NO synthase inhibition (L-NAME groups: CL-Name, P L-name). or not manipulated (groups CE, PE). Measurements and Main Results: Changes in ultrafiltration coefficients (ΔKf [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-MME virtually abolished the change in permeability (ΔKf: 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 (ΔKf) 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.

Original languageEnglish (US)
Pages (from-to)1872-1878
Number of pages7
JournalCritical care medicine
Issue number9
StatePublished - Sep 1 2004


  • Isolated perfused lung
  • Lung injury
  • Mechanical stress
  • Mechanical ventilation
  • Nitric oxide synthase inhibitor
  • Nitric oxitie
  • Oxidative stress


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