Effects of tumor necrosis factor alpha and vascular permeability factor on neovascularization of the rabbit ear flap.

Abstract

The survival of compromised skin flaps depends on neovascularization for their nutrition and metabolic waste removal. Our study investigated the effectiveness of angiogenic factors in accelerating peripheral neovascularization and in increasing skin flap viability. We elevated pedicled dorsal skin flaps on the ears of 23 New Zealand white rabbits, and the vascular pedicle was ligated to achieve partial flap necrosis. Fifteen flaps were treated with 0.1 micrograms/mL vascular permeability factor, and eight flaps were treated with 1.0 micrograms/mL tumor necrosis factor alpha. The ear flaps that were not treated with growth factor functioned in each rabbit as a normal saline control. The viability of skin flaps was observed visually and was measured by Cartesian planimetry using templates. Neovascularization was documented by microangiography and by histologic analysis of the flaps. Although the angiogenic factors accelerated neovascularization, increased flap survival was demonstrated only in those animals treated with vascular permeability factor that was supplied by an absorbable gelatin sponge. This experimental model, despite different levels of controls, contains multiple variables, including the use of an absorbable gelatin sponge, seroma formation, bioactivity of the angiogenic factors, optimal dosages and dosimetry, the need for a "blinded" format, and the validity of the histologic analysis. Additional investigation must be done and the experimental model itself must be improved before these apparently positive results may be accepted as clinically useful.