Long-term pulmonary and cardiovascular morbidities of neonatal hyperoxia exposure in mice

Renuka T. Menon, Amrit Kumar Shrestha, Corey L. Reynolds, Roberto Barrios, Binoy Shivanna

Research output: Contribution to journalArticle

11 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)119-124
Number of pages6
JournalInternational Journal of Biochemistry and Cell Biology
Volume94
DOIs
StatePublished - Jan 2018

Keywords

  • Bronchopulmonary dysplasia
  • Cardiac magnetic resonance imaging
  • Echocardiography
  • Hyperoxia
  • Long-term morbidities
  • Pulmonary hypertension

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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