Exposure to Supplemental Oxygen Downregulates Antioxidant Enzymes and Increases Pulmonary Arterial Contractility in Premature Lambs

Abstract

Background: The optimal oxygen concentration for the resuscitation of premature infants remains controversial. Objectives: We studied the effects of 21 versus 100% oxygen at initial resuscitation and also the effects of 24-hour exposure to 100% oxygen on arterial blood gases, oxidant lung injury, activities of lung antioxidant enzymes (AOEs) and isolated pulmonary artery (PA) contractility in preterm newborn lambs. Methods: Preterm lambs at 128 days’ gestation (term = 145 days) were delivered and ventilated with 21 (RAR; n = 5) or 100% oxygen (OXR; n = 5) for the first 30 min of life. Subsequently, FiO₂ was adjusted to maintain an arterial PO₂ (PaO₂) between 45 and 70 mm Hg for 24 h. A third group of lambs was mechanically ventilated with 100% oxygen for 24 h (OX24; n = 5). Results: Oxidized glutathione levels in whole blood correlated highly with PaO₂. Reduced to oxidized glutathione ratio was significantly different between the groups, the ratio increasing with decreasing oxygen exposure. The OX24 group had significantly higher activities of lipid hydroperoxide and myeloperoxidase and significantly lower activities of superoxide dismutase, catalase and glutathione peroxidase in the lung at 24 h. Activities of AOEs correlated inversely with alveolar PO₂. PA contractility to norepinephrine and KCl was greater with increasing oxygen exposure. Pretreatment with superoxide dismutase and catalase significantly reduced PA contractility in the OXR and OX24 groups, but not in the RAR group. Conclusions: We conclude that ventilated premature lambs are unable to appropriately increase AOE activity in response to hyperoxia and that increasing exposure to oxygen aggravates systemic oxidant stress, oxidant lung injury and pulmonary arterial contractility in these lambs.

Exposure to Supplemental Oxygen and Its Effects on Oxidative Stress and Antioxidant Enzyme Activity in Term Newborn Lambs

“…These results were similar to that reported previously in preterm lambs (12). The mean FiO 2 was 0.21 to 0.25 in the RAR group and 0.24 to 0.30 in the OXR group beyond the first hour of life.…”

“…Term lambs can induce AOE activity at 24 h in the presence of maximal hyperoxia, suggesting the maturation of these pathways. Preterm newborn lambs fail to up-regulate AOE activities at 24 h in contrast to term lambs (12). The response of AOE activity in the lung to the presence of hyperoxia varies in different species.…”

Cerebral Oxygenation and Oxygen Extraction in the Preterm Infant during Desaturation: Effects of Increasing FiO₂ to Assist Recovery

“…One has to consider that the accepted arterial pO 2 values in the newborn preterm baby are substantially higher than the physiologic (in utero) norm for the same post-conceptional age and that there are poor enzymatic and cellular anti-oxidant defenses [38][39][40][41] . In the immature baby, hyperoxia interferes with vascular development of the lungs and the eyes and is capable of causing cell death in these organs [10,[40][41][42][43][44][45] . There is an growing body of evidence that exposure to an excess of oxygen may be equally damaging to the developing brain [12][13][14][15] .…”

Inflammatory Mediators in the Immunobiology of Bronchopulmonary Dysplasia

“…In ventilated premature lambs, exposure to 100% oxygen for 24 h compared to PRN oxygen exposed actually resulted in a decrease in lung homogenate SOD, catalase, and glutathione peroxidase activity. Lung AOE activity was inversely related to alveolar oxygen exposure [169].…”