title: Progressive Vascular Functional and Structural Damage in a Bronchopulmonary Dysplasia Model in Preterm Rabbits Exposed to Hyperoxia.
abstract: 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.
authors: Department of Development and Regeneration, Group Biomedical Sciences, KU Leuven, 3000 Leuven, Belgium. juliojimenez@gmail.com.|Department of Obstetrics and Gynaecology, Clínica Alemana Universidad del Desarrollo, 7650568 Santiago, Chile. juliojimenez@gmail.com.
authors: Julio
authors: J
authors: Jiménez
authors: Department of Development and Regeneration, Group Biomedical Sciences, KU Leuven, 3000 Leuven, Belgium. jute.richter@uzleuven.be.
authors: Jute
authors: J
authors: Richter
authors: Department of Pediatrics, Ehime Prefectural Central Hospital, 790-0024 Ehime, Japan. ctnagatomo@gmail.com.
authors: Taro
authors: T
authors: Nagatomo
authors: Department of Development and Regeneration, Group Biomedical Sciences, KU Leuven, 3000 Leuven, Belgium. thomas.1.salaets@uzleuven.be.
authors: Thomas
authors: T
authors: Salaets
authors: Respiratory Division, Department of Clinical and Experimental Medicine, University of Leuven, 3000 Leuven, Belgium. Rozenn.Quarck@kuleuven.be.
authors: Rozenn
authors: R
authors: Quarck
authors: Respiratory Division, Department of Clinical and Experimental Medicine, University of Leuven, 3000 Leuven, Belgium. allard.wagenaar@kuleuven.be.
authors: Allard
authors: A
authors: Wagennar
authors: Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong University, 250021 Jinan, China. whmeisd@163.com.
authors: Hongmei
authors: H
authors: Wang
authors: Centre for Environment and Health, Department of Public Health and Primary Care, KU Leuven, 3000 Leuven, Belgium. Jeroen.Vanoirbeek@kuleuven.be.
authors: Jeroen
authors: J
authors: Vanoirbeek
authors: Department of Development and Regeneration, Group Biomedical Sciences, KU Leuven, 3000 Leuven, Belgium. jan.deprest@uzleuven.be.|Department of Obstetrics and Gynaecology, University College London, WC1E 6HX London, UK. jan.deprest@uzleuven.be.
authors: Jan
authors: J
authors: Deprest
authors: Division of Woman and Child, University Hospitals Leuven, 3000 Leuven, Belgium. jaan.toelen@uzleuven.be.
authors: Jaan
authors: J
authors: Toelen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001997:Bronchopulmonary Dysplasia / Q000209:etiology* / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D006801:Humans; D018496:Hyperoxia / Q000150:complications*; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D008168:Lung / Q000098:blood supply* / Q000473:pathology* / Q000503:physiopathology; D011650:Pulmonary Alveoli / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D011651:Pulmonary Artery / Q000473:pathology / Q000503:physiopathology; D011817:Rabbits; D012129:Respiratory Function Tests
keywords: animal models; bronchopulmonary dysplasia; lung chronic disease; lung function; rabbit