The pulmonary effect of nitric oxide synthase inhibition following endotoxemia in a swine model
H. Ogura, P. J. Offner, D. Saitoh, B. S. Jordan, A. A. Johnson, B. A. Pruitt Jr and W. G. Cioffi Jr
US Army Institute of Surgical Research, Department of Critical Care, Brooke Army Medical Center, Fort Sam Houston, Tex.
OBJECTIVE: To evaluate the pulmonary effect of treatment with
N-nitro-L-arginine methyl ester (NAME) with and without inhaled nitric
oxide (NO) in a swine model of endotoxemia. DESIGN: Randomized controlled
trial. SETTING: Laboratory. INTERVENTIONS: Following a 20-minute
intravenous infusion of Escherichia coli lipopolysaccharide (LPS) (200
micrograms/kg), animals were resuscitated with saline solution (1 mL/kg per
minute) and observed for 3 hours while mechanically ventilated (fraction of
inspired oxygen [FIO2], 0.6; tidal volume, 12 mL/kg; positive
end-expiratory pressure, 5 cm H2O). Group 1 (LPS, n = 6) received no
additional treatment; group 2 (NAME, n = 5) received NAME (3 mg/kg per
hour) for the last 2 hours; group 3 (NO, n = 6) received NAME (3 mg/kg per
hour) and inhaled NO (40 ppm) for the last 2 hours; and group 4 (control, n
= 5) received only saline solution without LPS. MAIN OUTCOME MEASURES:
Cardiopulmonary variables and blood gases were measured serially. The
multiple inert gas elimination technique was performed at 3 hours. The
wet-to-dry lung weight ratio was measured following necropsy. RESULTS:
Administration of LPS resulted in pulmonary arterial hypertension,
pulmonary edema, and hypoxemia with increased ventilation perfusion ratio
mismatching. None of these changes were attenuated by NAME treatment alone
but all were significantly improved by the simultaneous administration of
inhaled NO. CONCLUSIONS: Systemic NO synthase inhibition failed to restore
hypoxic pulmonary vasoconstriction following LPS administration. The
deleterious effects of endotoxemia on pulmonary function can be improved by
inhaled NO but not by systemic inhibition of NO synthase.
