Angiogenic effects of injected VEGF165 and sVEGFR-1 (sFLT-1) in a rat flap model

Abstract

Background: Injections of single-dose vascular endothelial growth factor (VEGF)(165) have been advocated as a therapeutic tool for angiogenesis in ischemic flaps. We challenged this thesis by employing both VEGF(165) and vascular endothelial growth factor receptor-1 (VEGFR-1) (for competitive inhibition of VEGF signal transduction) in different experimental settings of an ischemic rat flap model.

Material and methods: 80 isogenic rats were divided in two groups of 40 animals (groups 1A-1D and 2A-2D). The ischemic target was a 7 x 7-cm epigastric island flap, based on the right inferior epigastric pedicle. Group 1 received flap treatment 1 week prior to flap elevation by test substance injection into its flap panniculus carnosus: 1 ml NaCl 0.9% (1A), 1 ml Dulbecco's modified Eagle's medium (1B), 1.0 microg VEGF(165) (1C), and 10 microg sFLT-1 with 1.0 microg VEGF(165) (1D). sFLT-1 is a soluble receptor for VEGF and is able to prevent VEGF signaling through the cell surface receptor. Group 2 had the same flap treatment at the day of flap elevation.

Results: In group 1C we found the most vital flap tissue, without reaching significance. Compared with group 1D, however, significantly more flap tissue maintained vital. In groups 2A-2D, no significant results were found with respect to flap survival.

Conclusions: Local application of single-dose VEGF(165) 1 week prior to ischemia dose not have significant clinical angiogenic effects. In this experimental setting, VEGF(165)-induced angiogenic effects can be significantly inhibited by adding sFLT1 in vivo. A single-dose of VEGF(165) under ischemic conditions causes no significantly better flap survival in this model.