Anti-inflammatory effects of U74389F in a rat model of intestinal ischemia/reperfusion injury

Objective: To 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. Design: Prospective, randomized, controlled study. Setting: University research laboratory. Subjects: Adult, male Sprague-Dawley rats weighing between 200 and 300 g. Interventions: Groups (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 Results: Ischemia 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 B₄ and prostaglandin E₂ in response to ischemia and reperfusion. Conclusions: This study demonstrates that the mechanism of U74389F against mesenteric ischemia/reperfusion includes a delay and reduction of neutrophilic infiltrate, an inhibition of leukotriene B₄ production, and a facilitation of mucosal restitution.