The influence of different VEGF administration protocols on the perfusion of epigastric flaps in rats

In this study we investigated the impact of the time at which vascular endothelial growth factor (VEGF) was given on the overall survival of flaps and time of the achievement of full perfusion in the rat epigastric flap model. Epigastric flaps were raised in 144 rats. VEGF was given to 108 rats at different time points. Perioperatively blood flow, velocity, haemoglobin (Hb) concentration, and oxygen saturation were measured non-invasively using laser-Doppler spectrophotometry. On postoperative days 3, 5, 7, or 10, the pedicle of the flap was ligated. One week later, the flap was harvested for immunohistochemical assessment of the density of microvessels. Differences significant from those in the control group were found in all specimens 3 and 5 days after the first operation, whereas no differences in the area of necrosis were detected after 7 and 10 days. Preoperative values of measured Hb (p < 0.0001, 95% confidence interval (CI) 0.57 to 1.02), flow (p < 0.0001, 95% CI -0.32 to -0.13), and velocity (p < 0.0001, 95% CI 0.48 to 1.89) predicted necrosis. After ligation of the pedicle, SO₂ (p < 0.0001, 95% CI -1.12 to -0.83) and flow (p < 0.0001, 95% CI -0.38 to -0.26) were prognostic factors. The topical use of VEGF increases overall survival of flaps and decreases the time needed for a free flap to achieve full perfusion. The time of application of VEGF has no part in the postoperative course. The perfusion of vascularised free flaps in their wound beds was achieved between postoperative days 5 and 7 in the control group and postoperative days 3 and 5 after VEGF had been given.