SYSTEMIC NEUTROPHIL INTRINSIC 5-LIPOXYGENASE ACTIVITY AND CD18 RECEPTOR EXPRESSION LINKED TO REPERFUSION INJURY

Objective: To determine if systemic neutrophil intrinsic 5-lipoxygenas e (5-LO) inhibition correlates with decreased expression of surface ad hesion molecules and attenuation of ischemia-reperfusion (i/r) injury in guinea pig island skin flaps. Methods: Eighty-one adult female Hart ley guinea pigs were divided into one control group, three 2-hour isch emia groups, and four 10-hour ischemia groups. Island dorsal skin flap s were developed (except in the control group), and 2 hours before rep erfusion, zileutin (a 5-LO inhibitor) or vehicle was administered oral ly. Postreperfusion systemic neutrophil receptor expression, neutrophi l flap infiltration, and flap survival were measured. Neutrophils from whole blood were analyzed for CD18 containing surface receptor expres sion using monoclonal antibodies and cell associated fluorescence. Neu trophil infiltration into a distal centimeter squared of flap tissue w as assessed using myeloperoxidase antibodies, and flap survival was de termined within 7 days postoperatively. Results: Flaps in the treated 2- and 10-hour ischemic groups survived totally intact, while the untr eated 10-hour ischemic flaps underwent total necrosis. A significant m ain effect of the drug was detected using analysis of variance (ANOVA) (P = .0001). Surface receptor detection and neutrophil infiltration w ere significantly increased in the untreated animals. Conclusions: Zil euton, a 5-LO inhibitor, reduces adhesion receptor expression on syste mic neutrophils and attenuates i/r injury. Systemic neutrophil intrins ic 5-LO activity and CD18 receptor expression are linked to reperfusio n injury and may be fundamental events in its pathogenesis.