Postnatal hyperoxia exposure durably impairs right ventricular function and mitochondrial biogenesis

Kara N. Goss, Santosh Kumari, Laura H. Tetri, Greg Barton, Rudolf K. Braun, Timothy A. Hacker, Marlowe W. Eldridge

Research output: Contribution to journalArticlepeer-review

Abstract

Prematurity complicates 12% of births, and young adults with a history of prematurity are at risk to develop right ventricular (RV) hypertrophy and impairment. The long-term risk for pulmonary vascular disease, as well as mechanisms of RV dysfunction and ventricular-vascular uncoupling after prematurity, remain poorly defined. Using an established model of prematurity-related lung disease, pups from timed-pregnant Sprague Dawley rats were randomized to normoxia or hyperoxia (fraction of inspired oxygen, 0.85) exposure for the first 14 days of life. After aging to 1 year in standard conditions, rats underwent hemodynamic assessment followed by tissue harvest for biochemical and histological evaluation. Aged hyperoxia-exposed rats developed significantly greaterRVhypertrophy, associated with a40% increase inRVsystolic pressures. Although cardiac index was similar, hyperoxia-exposed rats demonstrated a reduced RV ejection fraction and significant RV-pulmonary vascular uncoupling. Hyperoxia-exposed RV cardiomyocytes demonstrated evidence of mitochondrial dysregulation and mitochondrial DNA damage, suggesting potential mitochondrial dysfunction as a cause of RV dysfunction. Aged rats exposed to postnatal hyperoxia recapitulate many features of young adults born prematurely, including increased RV hypertrophy and decreased RV ejection fraction. Our data suggest that postnatal hyperoxia exposure results in mitochondrial dysregulation that persists into adulthood with eventual RV dysfunction. Further evaluation of long-term mitochondrial function is warranted in both animal models of premature lung disease and in human adults who were born preterm.

Original languageEnglish (US)
Pages (from-to)609-619
Number of pages11
JournalAmerican journal of respiratory cell and molecular biology
Volume56
Issue number5
DOIs
StatePublished - May 2017
Externally publishedYes

Keywords

  • Mitochondrial biogenesis
  • Prematurity
  • Pulmonary hypertension

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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