OXIDANT STRESS RESPONSES IN PREMATURE-INFANTS DURING EXPOSURE TO HYPEROXIA

To assess oxidant stress responses in newborn infants treated with ele vated concentrations of oxygen, we measured plasma concentrations of g lutathione (GSH) and glutathione disulfide (GSSG) in newborn infants r anging from 23 to 42 wk gestational age. All infants recruited into th e study were mechanically ventilated and had catheters placed in their umbilical arteries as 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. We observed plasma concentrations of GSSG in these infants that were frequently an order of magnitude higher th an the 0.1 to 0.3 muM we find in adults. Interestingly, plasma GSSG co ncentrations were inversely correlated to the inspired oxygen tensions . This effect appeared to arise from the patient selection criteria wh ereby, of the infants studied, those breathing the lowest partial pres sures of oxygen were the smallest and gestationally youngest. A second observation was that plasma concentrations of GSH in the premature in fants were substantially, indeed often dramatically, lower than we hav e observed in adult humans (6 to 10 muM). Finally, we found that in pa tients with both umbilical arterial and umbilical venous catheters art erial GSSG concentrations were consistently higher than venous concent rations; conversely, arterial GSH concentrations were lower than venou s concentrations. The elevated GSSG concentrations we observed in thes e 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 th ese infants suggest that at least some of the increased plasma GSSG or iginates in the lung. The low plasma GSH concentrations we observed in these same infants suggest deficiencies in an antioxidant that has be en shown in numerous animal studies to be critical for prevention of h yperoxia-induced lung injury. Finally, the negative arteriovenous grad ients of GSH concentrations across the lung provide the first evidence in humans for pulmonary uptake of GSH.