The effects of VEGF on survival of a random flap in the rat: examination of various routes of administration

The purpose of the present study was to determine the effects of vascular endothelial growth factor (VEGF) on survival of a full thickness random pattern, McFarlane musculocutaneous flap in the rat. In addition, this study examined a number of different methods of VEGF delivery in an attempt to determine the most effective route of administration. A 2 × 8 cm full thickness dorsal flap with the pedicle remaining attached at the anterior end was elevated in 72 male Sprague–Dawley rats. The rats were randomised into six groups and immediately received the following treatment: Group I (n = 12): systemic VEGF injection into the femoral vein (50 μg/ml); Group II (n = 10): multiple systemic VEGF injections at 0, 24 and 48 h post flap elevation (50 μg/ml); Group III (n = 12): subdermal VEGF injection into the flap (1 μg/ml); Group IV (n = 12): subfascial VEGF injections into the recipient bed (1 μg/ml); Group V (n = 10): topical VEGF onto the recipient bed (1 μg/ml); Group VI (n = 16): control group with no treatment. Following 5 days recovery, the area of flap survival was measured. Mean flap survival ranged from 91% in Group II to 78% in Group V, and was significantly greater in all experimental groups (P< 0.001 for Groups I–IV and P< 0.05 for Group V) as compared to the control group (mean survival of 66%). The only significant difference between the experimental groups was between the mean survival in Group II and Group V (P< 0.05). Histological analysis demonstrated a qualitatively greater amount of granulation tissue and neovascularisation in the experimental groups. These results support the notion that VEGF rescues tissue at risk of hypoxic damage by inducing angiogenesis, and the use of growth factors such as VEGF holds promise as a method of increasing skin viability.