Faculty Collaboration Database

Acute and chronic changes in the control of breathing in a rat model of bronchopulmonary dysplasia. Am J Physiol Lung Cell Mol Physiol 2019 Mar 01;316(3):L506-L518

Date

01/18/2019

Pubmed ID

30652496

Pubmed Central ID

PMC6459293

DOI

10.1152/ajplung.00086.2018

Scopus ID

2-s2.0-85063934830 (requires institutional sign-in at Scopus site)   16 Citations

Abstract

Infants born very prematurely (<28 wk gestation) have immature lungs and often require supplemental oxygen. However, long-term hyperoxia exposure can arrest lung development, leading to bronchopulmonary dysplasia (BPD), which increases acute and long-term respiratory morbidity and mortality. The neural mechanisms controlling breathing are highly plastic during development. Whether the ventilatory control system adapts to pulmonary disease associated with hyperoxia exposure in infancy remains unclear. Here, we assessed potential age-dependent adaptations in the control of breathing in an established rat model of BPD associated with hyperoxia. Hyperoxia exposure ( FIO2 ; 0.9 from 0 to 10 days of life) led to a BPD-like lung phenotype, including sustained reductions in alveolar surface area and counts, and modest increases in airway resistance. Hyperoxia exposure also led to chronic increases in room air and acute hypoxic minute ventilation (V̇e) and age-dependent changes in breath-to-breath variability. Hyperoxia-exposed rats had normal oxygen saturation ( SpO2 ) in room air but greater reductions in SpO2 during acute hypoxia (12% O₂) that were likely due to lung injury. Moreover, acute ventilatory sensitivity was reduced at P12 to P14. Perinatal hyperoxia led to greater glial fibrillary acidic protein expression and an increase in neuron counts within six of eight or one of eight key brainstem regions, respectively, controlling breathing, suggesting astrocytic expansion. In conclusion, perinatal hyperoxia in rats induced a BPD-like phenotype and age-dependent adaptations in V̇e that may be mediated through changes to the neural architecture of the ventilatory control system. Our results suggest chronically altered ventilatory control in BPD.

Author List

Mouradian GC Jr, Alvarez-Argote S, Gorzek R, Thuku G, Michkalkiewicz T, Wong-Riley MTT, Konduri GG, Hodges MR

Authors

Matthew R. Hodges PhD Professor in the Physiology department at Medical College of Wisconsin
Girija Ganesh Konduri MD Chief, Professor in the Pediatrics department at Medical College of Wisconsin
Gary C. Mouradian PhD Assistant Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Age Factors
Animals
Bronchopulmonary Dysplasia
Disease Models, Animal
Hyperoxia
Hypertension, Pulmonary
Hypoxia
Lung
Lung Injury
Rats