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A PLACEBO CONTROLLED STUDY ON LUNG MECHANICS AFTER INTRA-AMNIOTIC INJECTION OF VEGF IN PRETERM RABBITS
  1. A Debeer2,
  2. S Mayer2,
  3. E Done2,
  4. X Roubliova2,
  5. G Naulaers1,
  6. P Carmeliet3,
  7. J Deprest2
  1. 1Neonatology, Department of Women and Child, UZ Leuven, Leuven, Belgium
  2. 2Centre for Surgical Technologies, Catholic University Leuven, Leuven, Belgium
  3. 3Centre of Transgene Technology and Gene Therapy, Catholic University Leuven, Leuven, Belgium

Abstract

Background Vascular endothelial growth factor (VEGF) is critical for angiogenesis, vasculogenesis and alveolar type II cell differentiation. We aimed to study the functional pulmonary effects of antenatal intra-amniotic VEGF administration in a preterm rabbit model.

Methods At 26 d gestational age (GA; term = 31–32 d), 60 μg recombinant rat VEGF164 in 250 μL vehicle or 250 μL placebo were injected intra-amniotically. Unexposed littermates served as internal controls At 28 d GA, fetuses were harvested (11 VEGF, 10 placebo, 10 control) for morphologic assessment or ventilated (11VEGF, 9 placebo, 8 control) with a Flexivent (Scireq, Montreal) ventilator allowing measurement of total lung capacity, resistance, compliance. Morphologic assessment includes airway and vascular morphometry and immunohistochemistry for Sp B, Flk 1, apoptotic (caspase 3) and proliferative markers (PCNA).

Results Lung mechanics as well as number of Flk-1 positive cells were higher in treated pups than in placebo and control animals (ANOVA p<0.05) (figure 1).

Conclusion Antenatal intra-amniotic injection of VEGF during the canalicular phase results in a significant improvement in lung mechanics and a higher number of Flk-1 positive cells at 28 d (saccular stage). This may be a new approach to improve lung maturation.

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