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 H2O at T1 and was subsequently (T2) either reduced to 15 cm H2O in the three low-pressure control groups (C-x) 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 congruent to20 ppm (inhaled NO groups: C-NO, P-NO), reduced by NO synthase inhibition (L-NAME groups: CL-Nzme PL-Name), or not manipulated (groups C-E, P-E). Measurements and Main Results: Changes in ultrafiltration coefficients (DeltaK(f) [vascular permeability index: g(.)min(-1)-cm H(2)O(-1.)100 g(-1)]), bronchoalveolar lavage fluid 8-isoprostane, and NO, (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 (DeltaK(f): PL-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 PL-NAME groups was observed. The change in permeability (DeltaK(f)) correlated with bronchoalveolar lavage NOx (r(2) =.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.