Improvement of a long random skin flap survival by application of vascular endothelial growth factor in various ways of local administration in a rat model

Abstract

ABSTRACT Background: Vascular endothelial growth factor (VEGF) is a heparin-binding glycoprotein which plays a significant role in angiogenesis and vascular permeability. The effect of various ways of local administration of VEGF on random skin flap survival was studied, using flaps with a relatively high length (L) to width (W) ratio (5:1). Materials and Methods: An 1.5 × 7.5 cm dorsal skin flap with the pedicle orientated, centered, and remaining attached between the lower angles of the scapulae was elevated in 45 Wistar rats in different phases, depending on the group. Rats were divided in five groups of nine. In group A, injections of saline were administered, in equally divided spaces, into flap′s fascia and transposed to a created skin defect. In group B, injections of VEGF were applied subdermally, in equally divided spaces, within the limits of a predesigned flap, a week prior to flap dissection and transposition. In group C, injections of VEGF were applied into a recipient bed′s fascia just before flap raising and transposition. In group D, injections of VEGF were applied subdermally, only in the distal third of the flap and then the flap was transposed to a recipient area. Finally, in group E, injections of VEGF were applied in the flap intrafascially and in equally divided spaces and then again, the flap was transposed to a recipient area. A week after final flap raising and positioning, rats were euthanatised and flaps were excised. Specimens were photographed, measured, put in formalin 10% and were sent for histological and image analysis. Results: Mean flap survival percentage was 35.4% in group A, and 33.7% in group B. In groups C and D, the mean survival area was 56.3% and 80.4%, respectively. In group E, the mean flap survival percentage was 28.3%. Histological analysis demonstrated increased angiogenesis in groups C and D. Conclusions: VEGF application improved skin flap survival when injected subdermally in the distal third of a random skin flap or into the fascia of a recipient area even though the length-to-width ratio was high.