N-ACETYL CYSTEINE ATTENUATES ACUTE LUNG INJURY IN THE RAT

The development of the adult respiratory distress syndrome (ARDS) in t he critically ill patient is associated with a significant morbidity a nd mortality. The pulmonary dysfunction in ARDS is largely secondary t o neutrophil-mediated oxidant injury. The purpose of these studies is to examine the effect of the antioxidant N-acetyl cysteine (NAC) on a rodent model of lung injury. We postulated that NAC might attenuate lu ng injury following intratracheal challenge with endotoxin (lipopolysa ccharide; LPS). Male Sprague-Dawley rats were administered NAC systemi cally either before or after intratracheal administration of LPS. Lung injury was assessed by measuring the transpulmonary leakage of I-125- labeled albumin, pulmonary myeloperoxidase content, bronchoalveolar la vage fluid cell counts, pulmonary lipid peroxidation and histology. NA C administration significantly attenuated the LPS-induced increases in lung permeability (LPS: .24 +/- .08 vs. LPS + NAG: .12 +/- .03, p < . 05) and reduced the LPS-dependent increase in lipid peroxidation. Howe ver, total and differential bronchoalveolar lavage cell counts and mye loperoxidase content were not affected by-NAC pretreatment. Although n eutrophil influx was unaffected, neutrophil activation as assessed by surface CD11b expression and chemiluminescence was significantly downr egulated by NAG. Importantly, NAC administration up to 2 h after endot oxin challenge was still able to significantly ameliorate LPS-induced lung injury. Our data suggests that the attenuation of acute lung inju ry by NAC in our rodent model is related to free radical scavenging an d inhibition of the neutrophil oxidative burst, rather than by an effe ct on inflammatory cell migration. These results suggest novel approac hes for therapeutic interventions in acute lung injury.