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Int. J. Mol. Sci. 2016, 17(10), 1776;

Progressive Vascular Functional and Structural Damage in a Bronchopulmonary Dysplasia Model in Preterm Rabbits Exposed to Hyperoxia

Department of Development and Regeneration, Group Biomedical Sciences, KU Leuven, 3000 Leuven, Belgium
Department of Obstetrics and Gynaecology, Clínica Alemana Universidad del Desarrollo, 7650568 Santiago, Chile
Department of Pediatrics, Ehime Prefectural Central Hospital, 790-0024 Ehime, Japan
Respiratory Division, Department of Clinical and Experimental Medicine, University of Leuven, 3000 Leuven, Belgium
Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong University, 250021 Jinan, China
Centre for Environment and Health, Department of Public Health and Primary Care, KU Leuven, 3000 Leuven, Belgium
Department of Obstetrics and Gynaecology, University College London, WC1E 6HX London, UK
Division of Woman and Child, University Hospitals Leuven, 3000 Leuven, Belgium
Author to whom correspondence should be addressed.
Academic Editor: Shaker Mousa
Received: 16 August 2016 / Revised: 10 October 2016 / Accepted: 17 October 2016 / Published: 24 October 2016
(This article belongs to the Special Issue Vascular Biology and Therapeutics)
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Bronchopulmonary dysplasia (BPD) is caused by preterm neonatal lung injury and results in oxygen dependency and pulmonary hypertension. Current clinical management fails to reduce the incidence of BPD, which calls for novel therapies. Fetal rabbits have a lung development that mimics humans and can be used as a translational model to test novel treatment options. In preterm rabbits, exposure to hyperoxia leads to parenchymal changes, yet vascular damage has not been studied in this model. In this study we document the early functional and structural changes of the lung vasculature in preterm rabbits that are induced by hyperoxia after birth. Pulmonary artery Doppler measurements, micro-CT barium angiograms and media thickness of peripheral pulmonary arteries were affected after seven days of hyperoxia when compared to controls. The parenchyma was also affected both at the functional and structural level. Lung function testing showed higher tissue resistance and elastance, with a decreased lung compliance and lung capacity. Histologically hyperoxia leads to fewer and larger alveoli with thicker walls, less developed distal airways and more inflammation than normoxia. In conclusion, we show that the rabbit model develops pulmonary hypertension and developmental lung arrest after preterm lung injury, which parallel the early changes in human BPD. Thus it enables the testing of pharmaceutical agents that target the cardiovascular compartment of the lung for further translation towards the clinic. View Full-Text
Keywords: bronchopulmonary dysplasia; animal models; lung chronic disease; rabbit; lung function bronchopulmonary dysplasia; animal models; lung chronic disease; rabbit; lung function

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Jiménez, J.; Richter, J.; Nagatomo, T.; Salaets, T.; Quarck, R.; Wagennar, A.; Wang, H.; Vanoirbeek, J.; Deprest, J.; Toelen, J. Progressive Vascular Functional and Structural Damage in a Bronchopulmonary Dysplasia Model in Preterm Rabbits Exposed to Hyperoxia. Int. J. Mol. Sci. 2016, 17, 1776.

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