Biochemical evaluation of postsurgical wound repair: Prevention of intraperitoneal adhesion formation with ibuprofen

Abstract

Proteins central to normal wound repair, including collagen and proteoglycans, were extracted during postoperative mesothelial regeneration, then the quantitation was correlated to macroscopic observations of normal peritoneal reepithelialization and/or postoperative adhesion formation. Sixty-three New Zealand white female rabbits of reproductive age were prospectively assigned to either Group A, untreated control; Group B, which received intramuscular injections of ibuprofen, 70 mg/kg per injection (immediately and 6 hr after surgery); or Group C, which received 5 intramuscular injections of ibuprofen (4 hr before surgery, and immediately, 6, 12, and 18 hr after surgery). The right uterine horn underwent one of three standardized surgical traumas: (1) abrasion of the peritoneal surface with a scalpel until punctate bleeding developed, (2) ischemia of the uterine horn by removal of the collateral blood supply (devascularization), (3) crushing of the uterine horn by cross clamping for 3 min with a Kelley hemostat. Thereafter, 10 μCi of C-14-labeled glucosamine and 10 μCi of C-14-labeled proline were injected into the marginal ear vein of each rabbit. All rabbits underwent a laparotomy on the fifth postoperative day for evaluation of adhesion formation and tissue biopsy for protein extraction. No reduction in adhesion formation was found using a 2-dose postoperative treatment regimen. However, using a 70 mg/kg × 5-doses regimen in the immediate perioperative interval, a significant reduction in both adhesion formation and severe adhesion formation (both P < 0.025) were found following standardized surgical injury. The extent of adhesion formation was correlated with the extractable glycosaminoglycan and collagen concentrations. As determined by recovered glucosamine and proline, a positive correlation was apparent between the severity of adhesion grade and formation of new glycosaminoglycans or collagens. Thus, ibuprofen appears to inhibit adhesion formation through suppression of fibroproliferative inflammation.