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 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.


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.
Machens
Hans-Günther
HG
Clinic for Plastic, Hand and Reconstructive Surgery, Lübeck University Clinics, Lübeck, Germany. Machens@medinf.mu-luebeck.de
Salehi
Jila
J
Weich
Herbert
H
Münch
Susanne
S
Siemers
Frank
F
Krapohl
Björn D
BD
Herter
Kay-Henryk
KH
Krüger
Stefan
S
Reichert
Bert
B
Berger
Alfred
A
Vogt
Peter
P
Mailänder
Peter
P
D000818:Animals; D004247:DNA / Q000096:biosynthesis; D016228:Endothelial Growth Factors / Q000008:administration & dosage* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D006801:Humans; D007267:Injections; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage* / Q000378:metabolism; D019194:Ischemic Preconditioning; D008222:Lymphokines / Q000008:administration & dosage* / Q000378:metabolism; D023421:Models, Animal; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051381:Rats; D011917:Rats, Inbred Lew; D012995:Solubility; D013524:Surgical Flaps; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000008:administration & dosage* / Q000378:metabolism; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D004247:DNA; D040281:Vascular Endothelial Growth Factor Receptor-1