AMINOGUANIDINE ATTENUATES ENDOTOXIN-INDUCED ACUTE LUNG INJURY IN RABBITS

Objective: To assess the effect of aminoguanidine, a selective inducib le nitric oxide synthase inhibitor, on endotoxin-induced acute lung in jury in rabbits,Design: Prospective, blinded, controlled laboratory st udy. Setting: University research laboratory. Subjects: Twenty-eight m ale rabbits, Interventions: The animals were randomly assigned to rece ive one of four treatments (n = 7 for each group): infusion of saline only (S-S group), infusion of saline and aminoguanidine (S-AG group), infusion of Escherichia coli endotoxin (5 mg/kg over 60 mins) (E-S gro up), and infusion of endotoxin and aminoguanidine (E-AG group), Fiftee n minutes before infusion of endotoxin (E-S and E-AG groups) or saline (S-S and S-AG groups), the animals received an intravenous injection of 1 mg/kg of aminoguanidine (S-AG and E-AG groups) or saline (S-S and E-S groups), The same dose of aminoguanidine or saline was given 1 hr after the end of endotoxin or saline infusion, The lungs of the rabbi ts were ventilated with 40% oxygen. Measurements and Main Results: Hem odynamics, peripheral leukocyte counts, and Pao(2) were recorded durin g the ventilation period (6 hrs). After these observations were made, lung mechanics, cell fraction of bronchoalveolar lavage fluid, and con centrations of thromboxane A(2) and prostacyclin metabolites in bronch oalveolar lavage fluid were determined. The wet weight/dry weight rati o of the lung and albumin concentrations in bronchoalveolar lavage flu id were analyzed as indices of pulmonary edema, Endotoxin decreased th e lung compliance and Pao(2) and increased the wet weight/dry weight r atio, neutrophil counts, and albumin concentrations in bronchoalveolar lavage fluid, The bronchoalveolar lavage fluid concentrations of thro mboxane B-2 in bronchoalveolar lavage fluid were increased by infusion of endotoxin, Aminoguanidine attenuated these changes, Endotoxin caus ed extensive morphologic lung damage, which was lessened by aminoguani dine. Conclusions: Aminoguanidine given intravenously before and after endotoxin attenuated endotoxin-induced lung injury in rabbits. These findings suggest that inducible nitric oxide synthase inhibition may b e useful in the treatment of endotoxin induced lung injury, However, f urther studies are required to determine the optimal dosage of aminogu anidine, when the inhibitor is given alone as therapy after lung injur y.