The adverse effect of selective cyclooxygenase-2 inhibitor on random skin flap survival in rats.

Background: Cyclooxygenase-2(COX-2) inhibitors provide desired analgesic effects after injury or surgery, but evidences suggested they also attenuate wound healing. The study is to investigate the effect of COX-2 inhibitor on random skin flap survival.

Methods: The McFarlane flap model was established in 40 rats and evaluated within two groups, each group gave the same volume of Parecoxib and saline injection for 7 days. The necrotic area of the flap was measured, the specimens of the flap were stained with haematoxylin-eosin(HE) for histologic analysis. Immunohistochemical staining was performed to analyse the level of VEGF and COX-2 .

Results: 7 days after operation, the flap necrotic area ratio in study group (66.65 ± 2.81)% was significantly enlarged than that of the control group(48.81 ± 2.33)%(P <0.01). Histological analysis demonstrated angiogenesis with mean vessel density per mm(2) being lower in study group (15.4 ± 4.4) than in control group (27.2 ± 4.1) (P <0.05). To evaluate the expression of COX-2 and VEGF protein in the intermediate area II in the two groups by immunohistochemistry test .The expression of COX-2 in study group was (1022.45 ± 153.1), and in control group was (2638.05 ± 132.2) (P <0.01). The expression of VEGF in the study and control groups were (2779.45 ± 472.0) vs (4938.05 ± 123.6)(P <0.01).In the COX-2 inhibitor group, the expressions of COX-2 and VEGF protein were remarkably down-regulated as compared with the control group.

Conclusion: Selective COX-2 inhibitor had adverse effect on random skin flap survival. Suppression of neovascularization induced by low level of VEGF was supposed to be the biological mechanism.