Vascular Endothelial Mitochondrial Function Predicts Death or Pulmonary Outcomes in Preterm Infants

Vascular endothelial mitochondrial dysfunction contributes to the pathogenesis of several oxidant stress-associated disorders. Oxidant stress is a major contributor to the pathogenesis of bronchopulmonary dysplasia (BPD), a chronic lung disease of prematurity that often leads to sequelae in adult survivors.

This study was conducted to identify whether differences in mitochondrial bioenergetic function and oxidant generation in human umbilical vein endothelial cells (HUVECs) obtained from extremely preterm infants were associated with risk for BPD or death before 36 weeks postmenstrual age.

HUVEC oxygen consumption and superoxide and hydrogen peroxide generation were measured in 69 infants.

Compared with HUVECs from infants who survived without BPD, HUVECs obtained from infants who developed BPD or died had a lower maximal oxygen consumption rate (mean ± SEM, 107 ± 8 vs. 235 ± 22 pmol/min/30,000 cells; P < 0.001), produced more superoxide after exposure to hyperoxia (mean ± SEM, 89,807 ± 16,616 vs. 162,706 ± 25,321 MitoSOX Red fluorescence units; P < 0.05), and released more hydrogen peroxide into the supernatant after hyperoxia exposure (mean ± SEM, 1,879 ± 278 vs. 842 ± 119 resorufin arbitrary fluorescence units; P < 0.001).

Our results indicating that endothelial cells of premature infants who later develop BPD or die have impaired mitochondrial bioenergetic capacity and produce more oxidants at birth suggest that the vascular endothelial mitochondrial dysfunction seen at birth in these infants persists through their postnatal life and contributes to adverse pulmonary outcomes and increased early mortality.