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

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 H 2 O at T1 and was subsequently (T2) either reduced to 15 cm H 2 O in the three low-pressure control groups (C x ) or increased to 25 cm H 2 O 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: C NO , P NO ), reduced by NO synthase inhibition (L-NAME groups: C L-Name , P L-Name ), or not manipulated (groups C E , P E ). Measurements and Main Results: Changes in ultrafiltration coefficients (ΔK f [vascular permeability index: gmin -1 .cm H 2 O -1 .100 g -1 ]), bronchoalveolar lavage fluid 8-isoprostane, and NO x (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 (ΔK f : P L-Name (0.10 ± 0.03) vs. P NO [1.75 ± 1.10] and P E [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 P E and P L-NAME groups was observed. The change in permeability (ΔK f ) correlated with bronchoalveolar lavage NO x (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.