To test the influence of vascular endothelial growth factor (VEGF) on normal and ischemic wounds in a noncontractive dermal ulcer standardized model in the rabbit ear and to assay the levels of both VEGF and basic fibroblastic growth factor messenger RNA levels in normal and ischemic wounds at different intervals during the healing process.
Design and Interventions
Dermal ulcers were created in the normal and ischemic ears of 20 anesthetized young female New Zealand white rabbits. Either VEGF 121, VEGF 165 (30 µg per wound), or buffered saline solution alone was applied to each wound and covered. Wounds were harvested at day 7 or 10 and evaluated histologically. Twenty-four similar rabbits were wounded in the same manner and their untreated wounds were harvested at 1, 3, 7, and 10 days after wounding. The wounds were analyzed with reverse transcriptase polymerase chain reaction.
Main Outcome Measures
Histologic specimens were measured for amount of new epithelium and granulation tissue. Reverse transcriptase polymerase chain reaction was used to determine basic fibroblastic growth factor and VEGF messenger RNA expression.
Both isoforms of VEGF improved granulation tissue formation in both normal and ischemic wounds with a magnitude similar to other vulnerary agents tested in the past. Vascular endothelial growth factor application had no effect on new epithelium formation. In contrast to basic fibroblastic growth factor, VEGF messenger RNA levels were induced 4 fold by ischemia alone and 6 fold by wounding in both ischemic and normal wounds.
Vascular endothelial growth factor seems to be more important than basic fibroblastic growth factor during ischemic wound healing. Treatment of ischemic wounds with VEGF improves the deficit in wound healing produced by ischemia.