A novel nitric oxide scavenger decreases liver injury and improves survival after hemorrhagic shock

We tested the ability of a nitric oxide (NO) scavenger to reduce tissue inj ury in a rodent model of hemorrhagic shock. Rats were hemorrhaged to a mean arterial blood pressure (MAP) of 40 mmHg and then resuscitated when either 30% of their shed blood had been returned (group I) or after 100 min of co ntinuous shock (group 2). Selected animals were treated with the NO scaveng er NOX (30 mg.kg(-1).h(-1)) infused over 4 h. Hemorrhaged rats had a lower MAP after resuscitation compared with sham-shock control rats. NOX treatmen t significantly increased MAP after resuscitation from hemorrhage. Hemorrha gic shock also increased liver injury as reflected by elevated ornithine ca rbamoyltransferase (OCT) plasma levels, and NOX treatment significantly red uced OCT release. In addition, NOX was associated with significantly decrea sed hepatic neutrophil infiltration and improved 24-h survival (n. = 8 of 9 ) compared with saline-treated shock animals (n 3 of 9). These data suggest that excess NO mediates shock-induced tissue injury and that suppression o f NO availability with NO scavengers may reduce the pathophysiological sequ elae of severe hemorrhage.