Rat epigastric flap survival and VEGF expression after local copper application

Background: Copper has been used in wound healing since ancient times, and copper insufficiency seems to impair wound healing. Much less is known about the local effects of copper application on wound healing. Methods: The authors studied 30 male Sprague-Dawley rats weighing between 250 and 350 g for 5 days. Full-thickness random skin flaps, measuring 1.5 X 7.5 cm, were elevated on the epigastric region. The rats were randomized into two groups according to the local treatment that was used. In group 1 (20 animals), 1 ml of copper ointment was applied on the flap bed after flap suturing. In group 2 (10 animals), 1 ml of placebo ointment (petroleum jelly) was used. Intraperitoneal injection of 30 mg/kg body weight of Hypoxyprobe-1 was performed in each rat on the fourth postoperative day and all animals were killed 3 hours later. Histologic examination of the distal end of the flaps was used for detection of hypoxic tissue changes. Expression, density, and extent of vascular endothelial growth factor activity was detected with the aid of immunocytochemistry. Results: All rats survived throughout the study period. This experimental study showed that local application of copper at the random flap bed may promote wound-related angiogenesis by inducing vascular endothelial growth factor expression. The authors demonstrated statistically significant flap survival after local copper application at the flap bed. Conclusion: The marked benefits of copper application in flap survival in this experimental model may guarantee its clinical application in flaps with questionable viability.