ObjectivesTo determine the possible role of enteric bacteria-derived endotoxin in the pathogenesis of the lung injury and mortality in rats following hemorrhagic shock and resuscitation.DesignProspective, randomized study.SettingAnimal laboratory of an institute for research in traumatology.SubjectsMale Sprague-Dawley rats, weighing 450 to 480 g.InterventionsAnesthetized rats were subjected to a prolonged hemorrhagic shock (mean arterial pressure of 30 to 35 mm Hg for 180 mins) followed by resuscitation. A murine monoclonal antibody to lipopolysaccharide from Escherichia coli and Salmonella, WN1 222-5, was administered at a total dose of 5 mg/kg iv, starting at the onset of shock (WN1 group). The control group was treated similarly to the WN1 group but received saline at the same volume as WN1 222-5.Measurements and Main ResultsThe 48-hr mortality rate was significantly reduced by WN1 222-5 treatment (28.6% in the treatment group vs. 78.6% in the control group; p = .0169). The characteristic lung injury in this model was significantly reduced in the WN1 group, as assessed by microscopic histopathologic examination increase in lung wet weight (7.60 +/- 0.47 g/kg in the control group vs. 5.14 +/- 0.31 g/kg in the WN1 group; p = .0002), and pulmonary neutrophilic infiltration (myeloperoxidase activity: 1835 +/- 567 mU/g wet weight in the control group vs. 891 +/- 212 mU/g wet weight in the WN1 group).ConclusionsThese data suggest that a) endotoxin derived from enteric bacteria might play an important role in the pathogenesis of lung injury; and b) antiendotoxin agents, such as WN1 222-5, appear to protect against endogenous bacterial endotoxin-related disorders in severe hemorrhagic shock in rats. (Crit Care Med 1997; 25:1030-1036)