Neonatal hyperoxia exposure induces aortic biomechanical alterations and cardiac dysfunction in juvenile rats

Merline Benny, Diana R. Hernandez, Mayank Sharma, Keyvan Yousefi, Shathiyah Kulandavelu, Sunil Batlahally, Ronald Zambrano, Pingping Chen, Eliana C. Martinez, Augusto F. Schmidt, Lina A. Shehadeh, Roberto I. Vasquez-Padron, Shu Wu, Omaida C. Velazquez, Karen C. Young

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Supplemental oxygen (O2) therapy in preterm infants impairs lung development, but the impact of O2 on long-term systemic vascular structure and function has not been well-explored. The present study tested the hypothesis that neonatal O2 therapy induces long-term structural and functional alterations in the systemic vasculature, resulting in vascular stiffness observed in children and young adults born preterm. Newborn Sprague-Dawley rats were exposed to normoxia (21% O2) or hyperoxia (85% O2) for 1 and 3 weeks. A subgroup exposed to 3 weeks hyperoxia was recovered in normoxia for an additional 3 weeks. Aortic stiffness was assessed by pulse wave velocity (PWV) using Doppler ultrasound and pressure myography. Aorta remodeling was assessed by collagen deposition and expression. Left ventricular (LV) function was assessed by echocardiography. We found that neonatal hyperoxia exposure increased vascular stiffness at 3 weeks, which persisted after normoxic recovery at 6 weeks of age. These findings were accompanied by increased PWV, aortic remodeling, and altered LV function as evidenced by decreased ejection fraction, cardiac output, and stroke volume. Importantly, these functional changes were associated with increased collagen deposition in the aorta. Together, these findings demonstrate that neonatal hyperoxia induces early and sustained biomechanical alterations in the systemic vasculature and impairs LV function. Early identification of preterm infants who are at risk of developing systemic vascular dysfunction will be crucial in developing targeted prevention strategies that may improve the long-term cardiovascular outcomes in this vulnerable population.

Original languageEnglish (US)
Article numbere14334
JournalPhysiological Reports
Issue number1
StatePublished - Jan 1 2020


  • LV dysfunction
  • developmental programming
  • neonatal hyperoxia
  • systemic vascular stiffness

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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