Oxidant Stress Responses in Premature Infants during Exposure to Hyperoxia

Abstract

ABSTRACT. To assess oxidant stress responses in newborn infants treated with elevated concentrations of oxygen, we measured plasma concentrations of glutathione (GSH) and glutathione disulfide (GSSG) in newborn infants ranging from 23 to 42 wk gestational age. All infants recruited into the study were mechanically ventilated and had catheters placed in their umbilical arteries a s part of their normal clinical management. Blood samples were obtained on d 1,3, and 5 and weekly thereafter or until the catheters were removed. W e observed plasma concentrations of GSSG in these infants that were frequently an order of magnitude higher than the 0.1 to 0.3 pM we find in adults. Interestingly, plasma GSSG concentrations were inversely correlated to the inspired oxygen tensions. This effect appeared to arise from the patient selection criteria whereby, of the infants studied, those breathing the lowest partial pressures of oxygen were the smallest and gestationally youngest. A second observation was that plasma concentrations of G S H in the premature infants were substantially, indeed often dramatically, lower than we have observed in adult humans (6 to 10 pM). Finally, we found that in patients with both umbilical arterial and umbilical venous catheters arterial GSSG concentrations were consistently higher than venous concentrations; conversely, arterial GSI4 concentrations were lower than venous concentrations. The elevated GSSG concentrations we observed in these infants indicate marked oxidant stress responses in prematurely born infants, even in those infants exposed only to room air. The positive arteriovenous gradients of GSSG concentrations across the lungs of these infants suggest that a t least some of the increased plasma GSSG originates in the lung. The low plasma G S H concentrations we observed in these same infants suggest deficiencies in an antioxidant that has been shown in numerous animal studies to be critical for prevention of hyperoxia-induced lung injury. Finally, the negative arteriovenous gradients of G S H concentrations across the lung provide the first evidence in humans for pulmonary uptake of GSH. (Pediatr Res 34: 360-365,1993) Abbreviations Fi02, fraction inspired oxygen GGT, y-glutamyltranspeptidase GSH, glutathione GSSG, glutathione disulfide PAO~, alveolar oxygen tension Pao2, arterial oxygen tension

Maternal and fetal indicators of oxidative stress during intrauterine growth retardation (IUGR)

“…Free radical reactions have been evaluated in healthy term infants and critically iII preterm infants (4,24). In premature newborns, both antioxidative enzymes and the level of scavengers are lower (25,26). Complications of the newborns such as bronchopulmonary dysplasia, retinopathy of prematurity, subependymal and intraventricular hemorrhage and necrotizing enterocolitis are thought to be due to the increased susceptibility of the newborns to free radical injury (27).…”

Neonatal resuscitation for the preterm infant: evidence versus practice

“…radicals occurring in infants who are intrinsically deficient in enzymatic antioxidants such as superoxide dismutase, catalase and glutathione peroxidase. [18][19][20] Preterm rabbits are unable to upregulate deficient antioxidants, 21 and Silvers et al 22 have reported that low plasma antioxidant activity at birth in premature infants was an independent risk factor for mortality. It is known that, during hypoxia, metabolic alterations prime cells to produce free oxygen radicals when the cells are subsequently exposed to oxygen.…”

Early inflammation in the absence of overt infection in preterm neonates exposed to intensive care

“…Our study also lacks a causative mechanism to explain what triggers the early systemic inflammatory responses observed in absence of infection, which certainly deserves further investigation in larger cohorts. Although we have not directly measured oxidative stress, others have widely reported increases in plasma oxidant markers in infants exposed to supplemental oxygen [9,10,27,28]. The fact that anti-inflammatory medication marginally correlated with this early inflammation may reflect the tendency of clinicians to use more aggressive pharmacologic management in infants needing increased intensive care therapies, combined with a delayed anti-inflammatory effect of those drugs.…”