Exposure to supplemental oxygen downregulates antioxidant enzymes and increases pulmonary arterial contractility in premature lambs.
BACKGROUND
The optimal oxygen concentration for the resuscitation of premature infants remains controversial.


OBJECTIVE
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.
Center for Developmental Biology of the Lung, Department of Pediatrics, University at Buffalo, Buffalo, NY 14222-2006, USA.
Anupama
A
Patel
Satyan
S
Lakshminrusimha
Rita M
RM
Ryan
Daniel D
DD
Swartz
Huamei
H
Wang
Karen A
KA
Wynn
Vasanth H
VH
Kumar
D000818:Animals; D000831:Animals, Newborn; D002374:Catalase / Q000378:metabolism / Q000494:pharmacology; D004195:Disease Models, Animal; D015536:Down-Regulation; D004347:Drug Interactions; D005865:Gestational Age; D019803:Glutathione Disulfide / Q000097:blood; D066298:In Vitro Techniques; D008054:Lipid Peroxides / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000201:enzymology; D009638:Norepinephrine / Q000494:pharmacology; D010088:Oxidoreductases / Q000378:metabolism*; D010100:Oxygen / Q000008:administration & dosage* / Q000097:blood; D011189:Potassium Chloride / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000502:physiology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000201:enzymology; D012121:Respiration, Artificial; D012151:Resuscitation; D012756:Sheep; D013482:Superoxide Dismutase / Q000378:metabolism / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D008054:Lipid Peroxides; D011189:Potassium Chloride; D010088:Oxidoreductases; D002374:Catalase; D013482:Superoxide Dismutase; D010100:Oxygen; D019803:Glutathione Disulfide; D009638:Norepinephrine