Superoxide Dismutase Improves Oxygenation and Reduces Oxidation in Neonatal Pulmonary Hypertension
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. To compare the effect of intratrachea...
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| Veröffentlicht in: | American journal of respiratory and critical care medicine 2006-12, Vol.174 (12), p.1370-1377 |
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| creator | Lakshminrusimha, Satyan Russell, James A Wedgwood, Stephen Gugino, Sylvia F Kazzaz, Jeffrey A Davis, Jonathan M Steinhorn, Robin H |
| description | 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.
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.
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.
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.
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. |
| doi_str_mv | 10.1164/rccm.200605-676OC |
| format | Article |
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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.
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.
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.
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.</description><identifier>ISSN: 1073-449X</identifier><identifier>EISSN: 1535-4970</identifier><identifier>DOI: 10.1164/rccm.200605-676OC</identifier><identifier>PMID: 17008638</identifier><language>eng</language><publisher>New York, NY: Am Thoracic Soc</publisher><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Animals ; Animals, Newborn ; Arterial hypertension. Arterial hypotension ; Biological and medical sciences ; Blood and lymphatic vessels ; Cardiology. Vascular system ; Clinical manifestations. Epidemiology. Investigative techniques. Etiology ; Female ; G. Pulmonary Vascular Disease ; Humans ; Hypotension ; Infant, Newborn ; Intensive care medicine ; Isoprostanes - analysis ; Laboratory animals ; Lung - chemistry ; Male ; Medical sciences ; Newborn babies ; Nitric oxide ; Nitric Oxide - pharmacology ; Norepinephrine - pharmacology ; Ostomy ; Oxidation ; Oxidation-Reduction - drug effects ; Oxygen - metabolism ; Persistent Fetal Circulation Syndrome - physiopathology ; Pneumology ; Potassium Chloride - pharmacology ; Pulmonary arteries ; Pulmonary Artery - drug effects ; Pulmonary hypertension ; Pulmonary hypertension. Acute cor pulmonale. Pulmonary embolism. Pulmonary vascular diseases ; Reactive Oxygen Species ; Recombinant Proteins - pharmacology ; Sheep ; Smooth muscle ; Superoxide Dismutase - pharmacology ; Tyrosine - analogs & derivatives ; Tyrosine - analysis ; Vasoconstriction - drug effects ; Ventilators</subject><ispartof>American journal of respiratory and critical care medicine, 2006-12, Vol.174 (12), p.1370-1377</ispartof><rights>2007 INIST-CNRS</rights><rights>Copyright American Thoracic Society Dec 15, 2006</rights><rights>Copyright © 2006, American Thoracic Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c490t-713f90a45717736f08f52a5ef1e05e6fbc4dcacada0f17b7ec39063860b76d1b3</citedby><cites>FETCH-LOGICAL-c490t-713f90a45717736f08f52a5ef1e05e6fbc4dcacada0f17b7ec39063860b76d1b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,4011,4012,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18368462$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17008638$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lakshminrusimha, Satyan</creatorcontrib><creatorcontrib>Russell, James A</creatorcontrib><creatorcontrib>Wedgwood, Stephen</creatorcontrib><creatorcontrib>Gugino, Sylvia F</creatorcontrib><creatorcontrib>Kazzaz, Jeffrey A</creatorcontrib><creatorcontrib>Davis, Jonathan M</creatorcontrib><creatorcontrib>Steinhorn, Robin H</creatorcontrib><title>Superoxide Dismutase Improves Oxygenation and Reduces Oxidation in Neonatal Pulmonary Hypertension</title><title>American journal of respiratory and critical care medicine</title><addtitle>Am J Respir Crit Care Med</addtitle><description>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.
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.
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.
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.
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.</description><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Arterial hypertension. Arterial hypotension</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Cardiology. Vascular system</subject><subject>Clinical manifestations. Epidemiology. Investigative techniques. Etiology</subject><subject>Female</subject><subject>G. Pulmonary Vascular Disease</subject><subject>Humans</subject><subject>Hypotension</subject><subject>Infant, Newborn</subject><subject>Intensive care medicine</subject><subject>Isoprostanes - analysis</subject><subject>Laboratory animals</subject><subject>Lung - chemistry</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Newborn babies</subject><subject>Nitric oxide</subject><subject>Nitric Oxide - pharmacology</subject><subject>Norepinephrine - pharmacology</subject><subject>Ostomy</subject><subject>Oxidation</subject><subject>Oxidation-Reduction - drug effects</subject><subject>Oxygen - metabolism</subject><subject>Persistent Fetal Circulation Syndrome - physiopathology</subject><subject>Pneumology</subject><subject>Potassium Chloride - pharmacology</subject><subject>Pulmonary arteries</subject><subject>Pulmonary Artery - drug effects</subject><subject>Pulmonary hypertension</subject><subject>Pulmonary hypertension. Acute cor pulmonale. Pulmonary embolism. Pulmonary vascular diseases</subject><subject>Reactive Oxygen Species</subject><subject>Recombinant Proteins - pharmacology</subject><subject>Sheep</subject><subject>Smooth muscle</subject><subject>Superoxide Dismutase - pharmacology</subject><subject>Tyrosine - analogs & derivatives</subject><subject>Tyrosine - analysis</subject><subject>Vasoconstriction - drug effects</subject><subject>Ventilators</subject><issn>1073-449X</issn><issn>1535-4970</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNpdkVuP0zAQhSMEYi_wA3hBERK8oCwztmMnL0ioXHalFUVcJN4sx3FaV4ld7GR3--9xm4oFnjwaf3Nmjk6WPUO4QOTsTdB6uCAAHMqCC75cPMhOsaRlwWoBD1MNghaM1T9PsrMYNwBIKoTH2QkKgIrT6jRrvk1bE_ydbU3-3sZhGlU0-dWwDf7GxHx5t1sZp0brXa5cm3817aQPfdvOXevyz8YnRPX5l6kfUhl2-eUuqY7GxYQ8yR51qo_m6fE9z358_PB9cVlcLz9dLd5dF5rVMBYCaVeDYqVAISjvoOpKokrToYHS8K7RrNVKq1ZBh6IRRtMakgcOjeAtNvQ8ezvrbqdmMK02bgyql9tgh3SS9MrKf3-cXcuVv5EEEYHxJPDqKBD8r8nEUQ42atP3yhk_RckrQgk5gC_-Azd-Ci6Zk1jXnFSCYYJwhnTwMQbT_bkEQe7jk_v45ByfPMSXZp7_beF-4phXAl4eARW16rugnLbxnqsorxgniXs9c2u7Wt_aYGQcVN8nWZRqs1-MgkkkEqkA-hs6wLVo</recordid><startdate>20061215</startdate><enddate>20061215</enddate><creator>Lakshminrusimha, Satyan</creator><creator>Russell, James A</creator><creator>Wedgwood, Stephen</creator><creator>Gugino, Sylvia F</creator><creator>Kazzaz, Jeffrey A</creator><creator>Davis, Jonathan M</creator><creator>Steinhorn, Robin H</creator><general>Am Thoracic Soc</general><general>American Lung Association</general><general>American Thoracic Society</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20061215</creationdate><title>Superoxide Dismutase Improves Oxygenation and Reduces Oxidation in Neonatal Pulmonary Hypertension</title><author>Lakshminrusimha, Satyan ; Russell, James A ; Wedgwood, Stephen ; Gugino, Sylvia F ; Kazzaz, Jeffrey A ; Davis, Jonathan M ; Steinhorn, Robin H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c490t-713f90a45717736f08f52a5ef1e05e6fbc4dcacada0f17b7ec39063860b76d1b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Arterial hypertension. Arterial hypotension</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Cardiology. Vascular system</topic><topic>Clinical manifestations. Epidemiology. Investigative techniques. Etiology</topic><topic>Female</topic><topic>G. Pulmonary Vascular Disease</topic><topic>Humans</topic><topic>Hypotension</topic><topic>Infant, Newborn</topic><topic>Intensive care medicine</topic><topic>Isoprostanes - analysis</topic><topic>Laboratory animals</topic><topic>Lung - chemistry</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Newborn babies</topic><topic>Nitric oxide</topic><topic>Nitric Oxide - pharmacology</topic><topic>Norepinephrine - pharmacology</topic><topic>Ostomy</topic><topic>Oxidation</topic><topic>Oxidation-Reduction - drug effects</topic><topic>Oxygen - metabolism</topic><topic>Persistent Fetal Circulation Syndrome - physiopathology</topic><topic>Pneumology</topic><topic>Potassium Chloride - pharmacology</topic><topic>Pulmonary arteries</topic><topic>Pulmonary Artery - drug effects</topic><topic>Pulmonary hypertension</topic><topic>Pulmonary hypertension. Acute cor pulmonale. Pulmonary embolism. Pulmonary vascular diseases</topic><topic>Reactive Oxygen Species</topic><topic>Recombinant Proteins - pharmacology</topic><topic>Sheep</topic><topic>Smooth muscle</topic><topic>Superoxide Dismutase - pharmacology</topic><topic>Tyrosine - analogs & derivatives</topic><topic>Tyrosine - analysis</topic><topic>Vasoconstriction - drug effects</topic><topic>Ventilators</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lakshminrusimha, Satyan</creatorcontrib><creatorcontrib>Russell, James A</creatorcontrib><creatorcontrib>Wedgwood, Stephen</creatorcontrib><creatorcontrib>Gugino, Sylvia F</creatorcontrib><creatorcontrib>Kazzaz, Jeffrey A</creatorcontrib><creatorcontrib>Davis, Jonathan M</creatorcontrib><creatorcontrib>Steinhorn, Robin H</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>American journal of respiratory and critical care medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lakshminrusimha, Satyan</au><au>Russell, James A</au><au>Wedgwood, Stephen</au><au>Gugino, Sylvia F</au><au>Kazzaz, Jeffrey A</au><au>Davis, Jonathan M</au><au>Steinhorn, Robin H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Superoxide Dismutase Improves Oxygenation and Reduces Oxidation in Neonatal Pulmonary Hypertension</atitle><jtitle>American journal of respiratory and critical care medicine</jtitle><addtitle>Am J Respir Crit Care Med</addtitle><date>2006-12-15</date><risdate>2006</risdate><volume>174</volume><issue>12</issue><spage>1370</spage><epage>1377</epage><pages>1370-1377</pages><issn>1073-449X</issn><eissn>1535-4970</eissn><abstract>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.
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.
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.
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.
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.</abstract><cop>New York, NY</cop><pub>Am Thoracic Soc</pub><pmid>17008638</pmid><doi>10.1164/rccm.200605-676OC</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; American Thoracic Society (ATS) Journals Online; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection; Journals@Ovid Complete |
| subjects | Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Animals Animals, Newborn Arterial hypertension. Arterial hypotension Biological and medical sciences Blood and lymphatic vessels Cardiology. Vascular system Clinical manifestations. Epidemiology. Investigative techniques. Etiology Female G. Pulmonary Vascular Disease Humans Hypotension Infant, Newborn Intensive care medicine Isoprostanes - analysis Laboratory animals Lung - chemistry Male Medical sciences Newborn babies Nitric oxide Nitric Oxide - pharmacology Norepinephrine - pharmacology Ostomy Oxidation Oxidation-Reduction - drug effects Oxygen - metabolism Persistent Fetal Circulation Syndrome - physiopathology Pneumology Potassium Chloride - pharmacology Pulmonary arteries Pulmonary Artery - drug effects Pulmonary hypertension Pulmonary hypertension. Acute cor pulmonale. Pulmonary embolism. Pulmonary vascular diseases Reactive Oxygen Species Recombinant Proteins - pharmacology Sheep Smooth muscle Superoxide Dismutase - pharmacology Tyrosine - analogs & derivatives Tyrosine - analysis Vasoconstriction - drug effects Ventilators |
| title | Superoxide Dismutase Improves Oxygenation and Reduces Oxidation in Neonatal Pulmonary Hypertension |
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