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.


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.
Broccard
Alain F
AF
University of Minnesota, Pulmonary and Critical Care Division, Regions Hospital, St. Paul, MN, USA.
Feihl
François
F
Vannay
Christine
C
Markert
Michele
M
Hotchkiss
John
J
Schaller
Marie-Denise
MD
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*
D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester