| Superoxide dismutase improves oxygenation and reduces oxidation in neonatal pulmonary hypertension. | |
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MedLine Citation:
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PMID: 17008638 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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RATIONALE: Hyperoxic ventilation in the management of persistent pulmonary hypertension of the newborn (PPHN) can result in the formation of reactive oxygen species, such as superoxide anions, which can inactivate nitric oxide (NO) and cause vasoconstriction and oxidation. OBJECTIVE: To compare the effect of intratracheal recombinant human superoxide dismutase (rhSOD) and/or inhaled NO (iNO) on systemic oxygenation, contractility of pulmonary arteries (PAs), and lung reactive oxygen species (isoprostane, 3-nitrotyrosine) levels in neonatal lambs with PPHN. METHODS: Six newborn lambs with PPHN (induced by antenatal ductal ligation) were killed at birth. Twenty-six PPHN lambs were ventilated for 24 h with 100% O(2) alone (n = 6) or O(2) combined with rhSOD (5 mg/kg intratracheally) at birth (n = 4), rhSOD at 4 h of age (n = 5), iNO (20 ppm, n = 5), or rhSOD + iNO (n = 6). Contraction responses of fifth-generation PAs to norepinephrine and KCl, lung isoprostane levels, and 3-nitrotyrosine fluorescent intensity were measured. RESULTS: Systemic oxygenation was impaired in PPHN lambs and significantly improved (up to threefold) in both rhSOD groups with or without iNO. Oxygenation improved more rapidly with the combination of rhSOD + iNO compared with either intervention alone. Norepinephrine- and KCl-induced contractions and lung isoprostane levels were significantly increased by 100% O(2) compared with nonventilated newborn lambs with PPHN. Both rhSOD and iNO mitigated the increased PA contraction response and lung isoprostane levels. Intratracheal rhSOD decreased the enhanced lung 3-nitrotyrosine fluorescence observed with iNO therapy. CONCLUSION: Intratracheal rhSOD and/or iNO rapidly increase oxygenation and reduce both vasoconstriction and oxidation in newborn lambs with PPHN. This has important implications for clinical trials of rhSOD and iNO in newborn infants with PPHN. |
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Authors:
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Satyan Lakshminrusimha; James A Russell; Stephen Wedgwood; Sylvia F Gugino; Jeffrey A Kazzaz; Jonathan M Davis; Robin H Steinhorn |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2006-09-28 |
Journal Detail:
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Title: American journal of respiratory and critical care medicine Volume: 174 ISSN: 1073-449X ISO Abbreviation: Am. J. Respir. Crit. Care Med. Publication Date: 2006 Dec |
Date Detail:
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Created Date: 2006-12-12 Completed Date: 2007-01-26 Revised Date: 2010-07-06 |
Medline Journal Info:
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Nlm Unique ID: 9421642 Medline TA: Am J Respir Crit Care Med Country: United States |
Other Details:
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Languages: eng Pagination: 1370-7 Citation Subset: AIM; IM |
Affiliation:
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Department of Pediatrics, State University of New York at Buffalo, NY, USA. slakshmi@buffalo.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Animals, Newborn Female Humans Infant, Newborn Isoprostanes / analysis Lung / chemistry Male Nitric Oxide / pharmacology Norepinephrine / pharmacology Oxidation-Reduction / drug effects Oxygen / metabolism Persistent Fetal Circulation Syndrome / physiopathology* Potassium Chloride / pharmacology Pulmonary Artery / drug effects Reactive Oxygen Species Recombinant Proteins / pharmacology Sheep Superoxide Dismutase / pharmacology* Tyrosine / analogs & derivatives, analysis Vasoconstriction / drug effects |
| Grant Support | |
ID/Acronym/Agency:
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HL-54705/HL/NHLBI NIH HHS; R01 HL054705-10/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Isoprostanes; 0/Reactive Oxygen Species; 0/Recombinant Proteins; 10102-43-9/Nitric Oxide; 3604-79-3/3-nitrotyrosine; 51-41-2/Norepinephrine; 55520-40-6/Tyrosine; 7447-40-7/Potassium Chloride; 7782-44-7/Oxygen; EC 1.15.1.1/Superoxide Dismutase |
| Comments/Corrections | |
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