Vascular Endothelial Growth Factor Enhances Compensatory Lung Growth in Piglets

Duy T. Dao, Lorenzo Anez-Bustillos, Amy Pan, Alison A. O'Loughlin, Paul D. Mitchell, Gillian L. Fell, Meredith A. Baker, Bennet S. Cho, Prathima Nandivada, Arthur P. Nedder, Charles J. Smithers, Nancy Chen, Robert Comeau, Kevin Holmes, Susan Kalled, Angela Norton, Bohong Zhang, Mark Puder

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Vascular endothelial growth factor has been found to accelerate compensatory lung growth after left pneumonectomy in mice. The aim of this study was to determine the natural history and the effects of vascular endothelial growth factor on compensatory lung growth in a large animal model. Methods: To determine the natural history of compensatory lung growth, female Yorkshire piglets underwent a left pneumonectomy on days of life 10–11. Tissue harvest and volume measurement of the right lung were performed at baseline (n = 5) and on postoperative days 7 (n = 5), 14 (n = 4), and 21 (n = 5). For pharmacokinetic studies, vascular endothelial growth factor was infused via a central venous catheter, with plasma vascular endothelial growth factor levels measured at various time points. To test the effect of vascular endothelial growth factor on compensatory lung growth, 26 female Yorkshire piglets underwent a left pneumonectomy followed by daily infusion of vascular endothelial growth factor at 200 µg/kg or isovolumetric 0.9% NaCl (saline control). Lungs were harvested on postoperative day 7 for volume measurement and morphometric analyses. Results: Compared with baseline, right lung volume after left pneumonectomy increased by factors of 2.1 ± 0.6, 3.3 ± 0.6, and 3.6 ± 0.4 on postoperative days 7, 14, and 21, respectively. The half-life of VEGF ranged from 89 to 144 minutes. Lesser doses of vascular endothelial growth factor resulted in better tolerance, volume of distribution, and clearance. Compared with the control group, piglets treated with vascular endothelial growth factor had greater lung volume (P < 0.0001), alveolar volume (P = 0.001), septal surface area (P = 0.007) and total alveolar count (P = 0.01). Conclusion: Vascular endothelial growth factor enhanced alveolar growth in neonatal piglets after unilateral pneumonectomy.

Original languageEnglish (US)
Pages (from-to)1279-1286
Number of pages8
JournalSurgery (United States)
Volume164
Issue number6
DOIs
StatePublished - Dec 2018
Externally publishedYes

ASJC Scopus subject areas

  • Surgery

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