5 years ago

Structural and functional changes of the pulmonary vasculature after hypoxia exposure in the neonatal period - a new swine model of pulmonary vascular disease.

Dirk J Duncker, Daphne Merkus, Richard W B van Duin, Irwin K M Reiss, Claudio Sartori, Urs Scherrer, Daphne P M de Wijs-Meijler
Pulmonary vascular disease (PVD) represents an underestimated and increasing clinical burden in the neonatal period, but also later in life, when exercise-tolerance is decreased. Animal models performing long-term follow-up after a perinatal insult are lacking. This study aimed to develop and characterize a neonatal swine model with hypoxia-induced PVD, during long-term follow-up after re-exposure to normoxia, and to investigate the exercise response in this model. Piglets were exposed to a normoxic (N=10) or hypoxic environment (N=9) for four weeks. Neonatal hypoxia exposure resulted in pulmonary hypertension (PH). Mean pulmonary artery pressure (PAP) was elevated one day after re-exposure to normoxia (30.2 ± 3.3 mmHg vs. 14.3 ± 0.9 mmHg), and remained significantly higher in the second week (32.8 ± 3.8 mmHg vs. 21.4 ± 1.2 mmHg), accompanied by decreased exercise tolerance. Exercise resulted in a trend towards an exaggerated increase of PAP in the hypoxia-exposed animals (week 6, P=0.086). Although PH was transient, thickening of pulmonary arterioles was found at the end of follow-up. Furthermore, right ventricular dilation, and lower right ventricular fractional area change (RVFAC week 8, 40.0 ± 2.7% vs. 29.5 ± 4.7%) and tricuspid annular plane systolic excursion (TAPSE week 8, 27.0 ± 2.5 mm vs. 22.9 ± 2.1 mm) persisted during follow-up. Male animals showed more severe PVD than female animals. In conclusion, we developed a neonatal swine model that allows examination of the long-term sequelae of damage to the developing neonatal lung, the course of the disease, and the effect of therapy on long-term outcome.

Publisher URL: http://doi.org/10.1152/ajpheart.00362.2017

DOI: 10.1152/ajpheart.00362.2017

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