TY - JOUR
T1 - Long-term pulmonary and cardiovascular morbidities of neonatal hyperoxia exposure in mice
AU - Menon, Renuka T.
AU - Shrestha, Amrit Kumar
AU - Reynolds, Corey L.
AU - Barrios, Roberto
AU - Shivanna, Binoy
N1 - Funding Information:
This work was supported by National Institutes of Health grants: HD-073323 to B.S., U54 HG006348 to the Mouse Phenotyping Core at Baylor College of Medicine (BCM) , and P30DK056338 to the Digestive Disease Center Core at BCM , and grants from the American Heart Association BGIA-20190008 and American Lung Association RG-349917 to B.S.
Publisher Copyright:
© 2017 Elsevier Ltd
PY - 2018/1
Y1 - 2018/1
N2 - 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.
AB - 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.
KW - Bronchopulmonary dysplasia
KW - Cardiac magnetic resonance imaging
KW - Echocardiography
KW - Hyperoxia
KW - Long-term morbidities
KW - Pulmonary hypertension
KW - Male
KW - Feasibility Studies
KW - Ventricular Dysfunction, Right/diagnostic imaging
KW - Time Factors
KW - Myocardium/pathology
KW - Female
KW - Hyperoxia/physiopathology
KW - Disease Models, Animal
KW - Animals, Newborn
KW - Bronchopulmonary Dysplasia/physiopathology
KW - Mice, Inbred C57BL
KW - Lung/blood supply
KW - Organ Size
KW - Hypertension, Pulmonary/diagnostic imaging
KW - Pulmonary Circulation
KW - Stroke Volume
KW - Heart/diagnostic imaging
KW - Magnetic Resonance Imaging
KW - Animals
KW - Atmosphere Exposure Chambers
KW - Ultrasonography, Doppler, Pulsed
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UR - http://www.scopus.com/inward/citedby.url?scp=85037644253&partnerID=8YFLogxK
U2 - 10.1016/j.biocel.2017.12.001
DO - 10.1016/j.biocel.2017.12.001
M3 - Article
C2 - 29223466
AN - SCOPUS:85037644253
SN - 1357-2725
VL - 94
SP - 119
EP - 124
JO - International Journal of Biochemistry and Cell Biology
JF - International Journal of Biochemistry and Cell Biology
ER -