Curdiovnsculal-Re,rearch, T h R a y n~Suppnrt of preterm infants with ventilation and oxygen therapy frequently leads to Lhe development of chronic lung disease. Oxidative stress, rhmugh the generation of excess oxygen free radicals, is thought to play a major role in this condition. At present the radical species responsible for oxidative lung ~n j u r y is not known, and cKcctive antioxidant based therapies are not available. The purposc of this study was to determine whether hydroxyl rad~cals, potent reactive oxygen species, are ~nvolved in chronic oxidative lung injury. To obtain this information we developed a animal model of chronic lung injury using the pretcrm guinea pig and analyzed lung tissuc from these pups for o-tyrosine, a specific marker of hydroxyl radical attack. In normoxia control pups the pulmonary content of n-tyrosine was low during the first 4 wk of life (range 0.1 1-0.12% tyrosine). Pups Thc role of oxygen in the development of neonatal Iung disease is unequivocal (1). Since the initial pmposal by Gerschman et al.(Z), the evidencc implicating oxygen free radicals in hyperoxiainduced lung injury has increased steadily. In 1981 Freeman and Ctapo (3) demonstrated that hypcroxic-exposure resulted in increased oxygen radical production jn rat lungs. These investigators subsequently showed that augmentation of superoxide disrnutase in endotheljal cells prt?vented oxidative injury, implicating superoxide anions in the injury p r m s (4). These findings were examined in newborn infants with lung disease, and supcroxide dismutase was found to provide some benefit (5), reinforcing the free radical hypothesis but without providing any further information as to which radicals were involved. Pitkaenen et 01. (6) added further weight to this hypothesis when they reported increased ethane and pentane levels in expired air of ventilated neonates. Schlenzig er 01, (7) also reported increased urinary excretion of malondialdchyde in ventilated premature infants which corsetated with FiOz levcls. None of the above clinical studies provided information regarding the oxygen free radical species involved in neonatal lung injury. Indeed, similar studies in maintained in 85% oxygen were found to have increasing rung a-tyrosine over this period (d
METHODSAnimals. Virgin, female Hartley strain guinea pigs (500 g) obtained horn our colony west caged in pairs in a room