Antenatal fetal VEGF therapy to promote pulmonary maturation in a preterm rabbit model.
OBJECTIVE
To assess the effects of fetal tracheal administration of VEGF on pulmonary maturation in a preterm rabbit model.


METHODS
On day 26 (term=31days), fetal rabbits received recombinant rat VEGF (30microg in 70microL normal saline) or placebo (normal saline 70microL) intratracheally, with or without subsequent tracheal occlusion. Non-operated littermates served as internal controls. Fetuses were harvested on day 28 for morphometric study of the lungs or for mechanical ventilation and measurement of lung mechanics. In total, 96 fetuses from 42 does were used, 47 for ventilation and 49 for morphometry.


RESULTS
In fetuses receiving intratracheal VEGF, an increase in immunoreactivity for Flk-1 was observed throughout the lung parenchyma. Tracheal occlusion (TO) adversely affected pulmonary mechanics as compared to un-occluded controls. That effect is partly reversed by intratracheal VEGF. Intratracheal injection of VEGF without tracheal occlusion improves lung mechanics but no more than what was observed in placebo injected controls.


CONCLUSIONS
Antenatal intratracheal VEGF administration was associated with an increase in Flk-1 immunoreactivity. It also improves lung mechanics, however more so when the trachea is occluded. Without TO, the effects were comparable to placebo controls.
Debeer
A
A
Centre for Surgical Technologies, Faculty of Medicine, KU Leuven, Leuven, Belgium. anne.debeer@uzleuven.be <anne.debeer@uzleuven.be>
Sbragia
L
L
Vrancken
K
K
Hendriks
A
A
Roubliova
X
X
Jani
J
J
Naulaers
G
G
Carmeliet
P
P
Deprest
J
J
D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D005325:Fetal Organ Maturity / Q000187:drug effects* / Q000502:physiology; D005865:Gestational Age; D007442:Intubation, Intratracheal; D008168:Lung / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D011247:Pregnancy; D037701:Pulmonary Surfactant-Associated Protein B / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011994:Recombinant Proteins; D012129:Respiratory Function Tests; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D015415:Biomarkers; D037701:Pulmonary Surfactant-Associated Protein B; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D040301:Vascular Endothelial Growth Factor Receptor-2