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Published on: August 25, 2017
Long-term pulmonary and cardiovascular morbidities of neonatal hyperoxia exposure in mice
Renuka T Menon1, Amrit Kumar Shrestha1, Corey L Reynolds2
1Section of Neonatology, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Insights
Neonatal hyperoxia exposure in mice leads to lasting lung and heart problems, including pulmonary hypertension and right ventricular dysfunction, persisting into adulthood. This model is crucial for developing new therapies for infants with bronchopulmonary dysplasia.
Area of Science:
- Cardiovascular Research
- Pulmonary Medicine
- Neonatalogy
Background:
- Bronchopulmonary dysplasia (BPD) in infants often causes pulmonary hypertension (PH) and persistent right ventricular (RV) dysfunction.
- Identifying a suitable animal model is critical for developing effective therapeutic strategies for BPD-associated PH.
Purpose of the Study:
- To characterize the long-term cardiopulmonary morbidities in a mouse model of neonatal hyperoxia exposure.
- To evaluate the utility of advanced imaging techniques like cardiac magnetic resonance imaging (cMRI) for assessing chronic effects.
Main Methods:
- Wild-type (WT) mice were exposed to hyperoxia (70% O2) or normoxia (21% O2) for the first two weeks of life, followed by six weeks of normoxic recovery.
- Lung morphometry, echocardiography (Echo), and cMRI were employed at eight weeks to assess alveolarization, vascularization, PH, and RV function.
Main Results:
- Neonatal hyperoxia exposure resulted in persistent simplification of lung alveoli and pulmonary vasculature.
- Echocardiography and cMRI revealed sustained signs of PH and RV dysfunction, including increased RV pressure and mass, altered volumes, and reduced ejection fractions.
Conclusions:
- Neonatal hyperoxia in mice induces chronic cardiopulmonary morbidities that persist into adulthood.
- This mouse model effectively replicates long-term BPD-related PH and RV dysfunction, serving as a valuable platform for therapeutic development.
Abstract:
Pulmonary hypertension (PH) frequently occurs in infants with bronchopulmonary dysplasia (BPD), causing increased mortality and right ventricular (RV) dysfunction that persists into adulthood. A first step in developing better therapeutic options is identifying and characterizing an appropriate animal model. Previously, we characterized the short-term morbidities of a model in which C57BL/6J wild-type (WT) mice were exposed to 70% O2 (hyperoxia) during the neonatal period. Here, we aimed to determine the long-term morbidities using lung morphometry, echocardiography (Echo), and cardiac magnetic resonance imaging (cMRI). The major highlight of this study is the use of the state-of-the art imaging technique, cMRI, in mice to characterize the long-term cardiac effects of neonatal hyperoxia exposure. To this end, WT mice were exposed to 21% O2 (normoxia) or hyperoxia for two weeks of life, followed by recovery in normoxia for six weeks. Alveolarization, pulmonary vascularization, pulmonary hypertension, and RV function were quantified at eight weeks. We found that hyperoxia exposure resulted in persistent alveolar and pulmonary vascular simplification. Furthermore, the Echo and cMRI studies demonstrated that hyperoxia-exposed mice had signs of PH and RV dysfunction as indicated by increased RV pressure, mass, and end-systolic and -diastolic volumes, and decreased RV stroke volume and ejection fractions. Taken together, our results demonstrate that neonatal hyperoxia exposure in mice cause cardiopulmonary morbidities that persists into adulthood and provides evidence for the use of this model to develop novel therapies for BPD infants with PH.
