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

HG Machens, J Salehi, H Weich, S Münch… - Journal of Surgical …, 2003 - Elsevier
HG Machens, J Salehi, H Weich, S Münch, F Siemers, BD Krapohl, KH Herter, S Krüger…
Journal of Surgical Research, 2003Elsevier
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 …
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.
Elsevier