Montelukast Protects Axial Pattern Rat Skin Flaps Against Ischemia/Reperfusion Injury

Background. Recent studies have shown that neutrophils play an important role in the pathogenesis of reperfusion injury. Using an inferior epigastric artery skin flap as a flap ischemia/reperfusion (I/R) injury model, we investigated whether the administration of montelukast sodium, a selective reversible cysteinyl leukotriene 1 (Cy5LT1) receptor antagonist, decreases neutrophil infiltration and promotes flap survival. Methods. Eighteen rats were used and randomly divided into three groups (n = 6 for each group). Group I was the sham group and did not undergo ischemic insult; rather, normal saline (1mL) was administrated intraperitonealy (i.p.) 30 min before surgery and continued for 6 d. Group II (control) and Group III (montelukast) underwent 12 h of ischemic insult. For Group II, normal saline (1mL) was injected i.p. 30 min before the surgery and immediately before reperfusion, and this continued for 6 d. In Group III, 1mL of montelukast (10mg/kg) was injected i.p. and continued for 6 d. Malondialdehyde (MDA) and glutathione (GSH) levels and myeloperoxidase (MPO) enzyme activities were investigated. Histological evaluation was made to investigate the tissue neutrophil count. Survival areas were assessed at 7 d postoperatively. Results. Group III (montelukast- treated) showed a significantly higher survival rate than Group II (control) (P = 0.029) but a lower survival rate than Group I (sham). Histological and biochemical assays corroborated this data. Conclusion. This study suggests that montelukast CysLT1 receptor antagonist montelukast reversed I/R-induced oxidant responses and improved flap survival by inhibiting neutrophil infiltration and balancing oxidant and antioxidant status. (C) 2009 Elsevier Inc. All rights reserved.