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.

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.

VEGF application on rat skin flap survival.

BACKGROUND: Induction of angiogenesis has been shown to be mediated by a number of glycoproteins called growth factors. Growth factors control the growth, differentiation, and metabolism of cells. Vascular endothelial growth factor (VEGF) is believed to be the most potent regulator of this process. The effect of its exogenous administration on the distal third of a long random skin flap was examined. MATERIALS AND METHODS: Eighteen Wistar rats were divided into two groups of nine. Rats were anesthetized, and a skin flap, measuring 1.5 × 7.5 cm, was elevated at their dorsum. The flap was standardized by centering the pedicle between the lower angles of the scapulae and by using a frame with the previously mentioned dimensions. The length of the flap was five times greater than its width. In group A (n = 9), the flap was elevated, one milliliter of normal saline was injected subdermally, at the distal third, and it was sutured back at its original place. In group B (n = 9), the flap was elevated, injections of 10 µg of VEGF were administrated subdermally, at the distal third, and it was again sutured back. Rats were euthanized a week later and flaps were excised. All specimens were measured, photographed, put in formalin 10%, and were sent for image and histological analysis. Image analysis was used both for the estimation of viable area and for the calculation of mean vessel density per mm2. RESULTS: Necrotic areas of the flaps were clearly demarcated within a week's time. In group A, the mean flap survival percentage was 38.9%. In group B, the percentage was 80.4%. Histological analysis demonstrated angiogenesis in group B, with mean vessel density per mm2 being higher in group B than in group A. CONCLUSIONS: Administration of VEGF injections at the distal part of a long random skin flap (length to width ratio 5:1) has been shown to improve the survival rate of the flap and thus contributing to the salvage of greater peripheral segment of the flap. Neovascularization induced by exogenous VEGF seems to be the biological mechanism, which leads to the improvement of flap survival.

Pharmacokinetics of intravitreal bevacizumab (Avastin®) in rabbits.

PURPOSE: To describe the pharmacokinetics of intravitreal bevacizumab (Avastin®) in rabbits. METHODS: The right eye of 20 rabbits was injected intravitreally with 1.25 mg/0.05 mL bevacizumab. Both eyes of four rabbits each time were enucleated at days 1, 3, 8, 15, and 29. Bevacizumab concentrations were measured in serum, aqueous humor, and vitreous. RESULTS: Maximum vitreous (406.25 µg/mL) and aqueous humor (5.83 µg/mL) concentrations of bevacizumab in the right eye were measured at day 1. Serum bevacizumab concentration peaked at day 8 (0.413 µg/mL) and declined to 0.032 µg/mL at 4 weeks. Half-life values in right vitreous, right aqueous humor, and serum were 6.61, 6.51, and 5.87 days, respectively. Concentration of bevacizumab in the vitreous of the noninjected eye peaked at day 8 (0.335 ng/mL) and declined to 0.218 ng/mL at 4 weeks. In the aqueous humor of the noninjected eye, maximum concentration of bevacizumab was achieved at day 8 (1.6125 ng/mL) and declined (to 0.11 ng/mL) at 4 weeks. CONCLUSION: The vitreous half-life of 1.25 mg/0.05 mL intravitreal bevacizumab was 6.61 days in this rabbit model. Maximum concentrations of bevacizumab were reached at day 1 in both vitreous and aqueous humor of the right eye and at day 8 in the serum. Very low concentrations of bevacizumab were measured in the fellow noninjected eye.