ObjectiveTo investigate the role of eicosanoid generation and neutrophilic infiltration in the protective effects of U74389F against ischemia/reperfusion injury in the small intestines of rats.DesignProspective, randomized, controlled study.SettingUniversity research laboratory.SubjectsAdult, male Sprague-Dawley rats weighing between 200 and 300 g.InterventionsGroups (5-8) of rats treated with U74389F or vehicle were subjected to a sham operation and 30 mins of ischemia by occlusion of the superior mesenteric artery or 30 mins of ischemia followed by 60 or 120 mins of reperfusion. U74389F (2.5 mg/kg Iv) or vehicle (citrate buffer) were slowly injected 2 mins before ischemia.Measurements and Main ResultsIschemia significantly (p < .05) increased mucosal injury (0 [normal] to 5) in both U74389F and untreated rats. In contrast, U74389F significantly (p < .05) attenuated the severity of injury after reperfusion. In vehicle-treated rats, ischemia/reperfusion significantly reduced villus height in both U74389F and untreated groups. However, the surface epithelial layer was intact in the U74389F but not in the vehicle-treated group. In addition, compared with the vehicle-treated group, U74389F significantly reduced neutrophil infiltration and prevented the increase in leukotriene B4and prostaglandin E2in response to ischemia and reperfusion.ConclusionsThis study demonstrates that the mechanism of U74389F against mesenteric ischemia/reperfusion includes a delay and reduction of neutrophilic infiltrate, an inhibition of leukotriene B4production, and a facilitation of mucosal restitution. (Crit Care Med 1999; 27:764-770)