Exposure to supplemental oxygen downregulates antioxidant enzymes and increases pulmonary arterial contractility in premature lambs

Anupama Patel, Satyanarayana Lakshminrusimha, Rita M. Ryan, Daniel D. Swartz, Huamei Wang, Karen A. Wynn, Vasanth H. Kumar

Research output: Contribution to journalArticle

16 Citations (Scopus)

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, FiO 2 was adjusted to maintain an arterial PO2 (PaO 2) 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 PaO 2. 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.

Original languageEnglish (US)
Pages (from-to)182-192
Number of pages11
JournalNeonatology
Volume96
Issue number3
DOIs
StatePublished - Sep 1 2009
Externally publishedYes

Fingerprint

Down-Regulation
Antioxidants
Oxygen
Lung
Enzymes
Oxidants
Pulmonary Artery
Glutathione Disulfide
Lung Injury
Resuscitation
Catalase
Superoxide Dismutase
Hyperoxia
Lipid Peroxides
Glutathione Peroxidase
Premature Infants
Peroxidase
Norepinephrine
Gases
Newborn Infant

Keywords

  • Antioxidant enzymes
  • Arterial blood gases
  • Oxygen exposure
  • Premature lambs
  • Pulmonary artery
  • Resuscitation

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Developmental Biology

Cite this

Exposure to supplemental oxygen downregulates antioxidant enzymes and increases pulmonary arterial contractility in premature lambs. / Patel, Anupama; Lakshminrusimha, Satyanarayana; Ryan, Rita M.; Swartz, Daniel D.; Wang, Huamei; Wynn, Karen A.; Kumar, Vasanth H.

In: Neonatology, Vol. 96, No. 3, 01.09.2009, p. 182-192.

Research output: Contribution to journalArticle

Patel, Anupama ; Lakshminrusimha, Satyanarayana ; Ryan, Rita M. ; Swartz, Daniel D. ; Wang, Huamei ; Wynn, Karen A. ; Kumar, Vasanth H. / Exposure to supplemental oxygen downregulates antioxidant enzymes and increases pulmonary arterial contractility in premature lambs. In: Neonatology. 2009 ; Vol. 96, No. 3. pp. 182-192.
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T1 - Exposure to supplemental oxygen downregulates antioxidant enzymes and increases pulmonary arterial contractility in premature lambs

AU - Patel, Anupama

AU - Lakshminrusimha, Satyanarayana

AU - Ryan, Rita M.

AU - Swartz, Daniel D.

AU - Wang, Huamei

AU - Wynn, Karen A.

AU - Kumar, Vasanth H.

PY - 2009/9/1

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N2 - 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, FiO 2 was adjusted to maintain an arterial PO2 (PaO 2) 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 PaO 2. 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.

AB - 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, FiO 2 was adjusted to maintain an arterial PO2 (PaO 2) 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 PaO 2. 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.

KW - Antioxidant enzymes

KW - Arterial blood gases

KW - Oxygen exposure

KW - Premature lambs

KW - Pulmonary artery

KW - Resuscitation

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