THE PULMONARY EFFECT OF NITRIC-OXIDE SYNTHASE INHIBITION FOLLOWING ENDOTOXEMIA IN A SWINE MODEL

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 tri al. Setting: Laboratory. Interventions: Following a 20-minute intraven ous infusion of Escherichia coli lipopolysaccharide (LPS) (200 mu g/kg ), animals were resuscitated with saline solution (1 ml/kg per minute) and observed for 3 hours while mechanically ventilated (fraction of i nspired oxygen [FIO2], 0.6; tidalvolume, 12 mL/kg; positive end-expira tory pressure, 5 cm H2O). Group 1 (LPS, n=6) received no additional tr eatment; 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 i nhaled NO (40 ppm) for the last 2 hours; and group 4 (control, n=5) re ceived only saline solution without LPS. Main Outcome Measures: Cardio pulmonary variables and blood gases were measured serially. The multip le inert gas elimination technique was performed at 3 hours. The wet-t o-dry lung weight ratio was measured following necropsy. Results: Admi nistration of LPS resulted in pulmonary arterial hypertension, pulmona ry edema, and hyperemia with increased ventilation perfusion ratio mis matching. None of these changes were attenuated by NAME treatment alon e but all were significantly improved by the simultaneous administrati on of inhaled NO. Conclusions: Systemic NO synthase inhibition failed to restore hypoxic pulmonary vasoconstriction following LPS administra tion. The deleterious effects of endotoxemia on pulmonary function can be improved by inhaled NO but not by systemic inhibition of NO syntha se.