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

Abstract

Supplemental oxygen (O 2 ) therapy in preterm infants impairs lung development, but the impact of O 2 on long-term systemic vascular structure and function has not been well-explored. The present study tested the hypothesis that neonatal O 2 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% O 2 ) or hyperoxia (85% O 2 ) 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. K E Y W O R D Sdevelopmental programming, LV dysfunction, neonatal hyperoxia, systemic vascular stiffness

Programming of Vascular Dysfunction by Maternal Stress: Immune System Implications

“…Still, larger vessels in these animals exhibit remodeling characterized by augmented collagen deposition, and reduced elastin ( Walton et al, 2016 ). Similar observations were made in rat aortas, along with cardiac remodeling ( Benny et al, 2020 ). IUGR also favors arterial remodeling in the adult offspring, as observed in sheep ( Dodson et al, 2014 ).…”

Impact of the Vulnerable Preterm Heart and Circulation on Adult Cardiovascular Disease Risk

“… 38 Disruption of elastin synthesis at the end of gestation or with preterm birth may increase arterial stiffness as supported by experimental models. 39 , 40 Desmosine levels—an elastin breakdown product—were also elevated in a cohort of young adults born extremely preterm, though they did not correlate with PWV or augmentation index. 41 Boardman et al 34 performed a detailed study of major systemic arteries in 102 young adults born very preterm at an average of 30 weeks’ gestation compared with 102 term-born age-matched controls.…”

Cardiac Left Ventricle Mitochondrial Dysfunction After Neonatal Exposure to Hyperoxia: Relevance for Cardiomyopathy After Preterm Birth

“…11,12,14 When birth is preterm, an immature myocardium must undertake the transition. Clinical [3][4][5][6][7] and experimental 8,9,15,37 studies have demonstrated morphological and functional cardiac alterations in adults born preterm, as well as in animal models 37,38 simulating conditions associated with preterm birth. However, mechanisms of cardiac alterations after preterm birth are not well known.…”