Intermittent hypoxia during recovery from neonatal hyperoxic lung injury causes long-term impairment of alveolar development: A new rat model of BPD.

Journal Article (Journal Article)

Bronchopulmonary dysplasia (BPD) is a chronic lung injury characterized by impaired alveologenesis that may persist into adulthood. Rat models of BPD using varying degrees of hyperoxia to produce injury either cause early mortality or spontaneously recover following removal of the inciting stimulus, thus limiting clinical relevance. We sought to refine an established rat model induced by exposure to 60% O2 from birth by following hyperoxia with intermittent hypoxia (IH). Rats exposed from birth to air or 60% O2 until day 14 were recovered in air with or without IH (FIO2 = 0.10 for 10 min every 6 h) until day 28 Animals exposed to 60% O2 and recovered in air had no evidence of abnormal lung morphology on day 28 or at 10-12 wk. In contrast, 60% O2-exposed animals recovered in IH had persistently increased mean chord length, more dysmorphic septal crests, and fewer peripheral arteries. Recovery in IH also increased pulmonary vascular resistance, Fulton index, and arterial wall thickness. IH-mediated abnormalities in lung structure (but not pulmonary hypertension) persisted when reexamined at 10-12 wk, accompanied by increased pulmonary vascular reactivity and decreased exercise tolerance. Increased mean chord length secondary to IH was prevented by treatment with a peroxynitrite decomposition catalyst [5,10,15,20-Tetrakis(4-sulfonatophenyl)-21H,23H-porphyrin iron (III) chloride, 30 mg/kg/day, days 14-28], an effect accompanied by fewer inflammatory cells. We conclude that IH during recovery from hyperoxia-induced injury prevents recovery of alveologenesis and leads to changes in lung and pulmonary vascular function lasting into adulthood, thus more closely mimicking contemporary BPD.

Full Text

Duke Authors

Cited Authors

  • Mankouski, A; Kantores, C; Wong, MJ; Ivanovska, J; Jain, A; Benner, EJ; Mason, SN; Tanswell, AK; Auten, RL; Jankov, RP

Published Date

  • February 1, 2017

Published In

Volume / Issue

  • 312 / 2

Start / End Page

  • L208 - L216

PubMed ID

  • 27913427

Pubmed Central ID

  • PMC5336579

Electronic International Standard Serial Number (EISSN)

  • 1522-1504

Digital Object Identifier (DOI)

  • 10.1152/ajplung.00463.2016


  • eng

Conference Location

  • United States