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

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 VEGF₁₆₅ 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 × 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 μg VEGF₁₆₅ (1C), and 10 μg sFLT-1 with 1.0 μg VEGF₁₆₅ (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 VEGF₁₆₅ 1 week prior to ischemia dose not have significant clinical angiogenic effects. In this experimental setting, VEGF₁₆₅-induced angiogenic effects can be significantly inhibited by adding sFLT1 in vivo. A single-dose of VEGF₁₆₅ under ischemic conditions causes no significantly better flap survival in this model.