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3′,4′‐Dihydroxyflavonol reduces infarct size and injury associated with myocardial ischaemia and reperfusion in sheep
The antioxidant properties of flavonols in vivo and their potential benefits in myocardial ischaemia/reperfusion (I/R) injury have been little investigated. We evaluated the ability of a synthetic flavonol, 3′,4′‐dihydroxyflavonol (DiOHF) to scavenge superoxide in post‐I/R myocardium and to prevent...
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| Published in: | British journal of pharmacology 2004-06, Vol.142 (3), p.443-452 |
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| container_title | British journal of pharmacology |
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| creator | Wang, Sheng Dusting, Gregory J May, Clive N Woodman, Owen L |
| description | The antioxidant properties of flavonols in vivo and their potential benefits in myocardial ischaemia/reperfusion (I/R) injury have been little investigated. We evaluated the ability of a synthetic flavonol, 3′,4′‐dihydroxyflavonol (DiOHF) to scavenge superoxide in post‐I/R myocardium and to prevent myocardial I/R injury.
Anaesthetized sheep were studied in four groups (n=5–6): control, ischaemic preconditioning (IPC), vehicle and DiOHF (before reperfusion, 5 mg kg−1, i.v.). The left anterior descending coronary artery was occluded distal to the second diagonal branch for 1 h followed by 2 h of reperfusion. Infarct size, myocardial function, NADPH‐activated superoxide generation and biochemical markers of injury were measured.
DiOHF (10−8–10−4 M) incubated in vitro with post‐I/R myocardium from the vehicle group suppressed superoxide production dose‐dependently. DiOHF administered in vivo also significantly reduced superoxide generation in vitro.
DiOHF and IPC markedly reduced infarct size, which was 73±2% of the area at risk in vehicle, 50±4% in DiOHF, 75±5% in control and 44±4% in IPC. Post‐I/R segment shortening within the ischaemic zone was greater in DiOHF (2.3±0.7%; P |
| doi_str_mv | 10.1038/sj.bjp.0705815 |
| format | article |
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Anaesthetized sheep were studied in four groups (n=5–6): control, ischaemic preconditioning (IPC), vehicle and DiOHF (before reperfusion, 5 mg kg−1, i.v.). The left anterior descending coronary artery was occluded distal to the second diagonal branch for 1 h followed by 2 h of reperfusion. Infarct size, myocardial function, NADPH‐activated superoxide generation and biochemical markers of injury were measured.
DiOHF (10−8–10−4 M) incubated in vitro with post‐I/R myocardium from the vehicle group suppressed superoxide production dose‐dependently. DiOHF administered in vivo also significantly reduced superoxide generation in vitro.
DiOHF and IPC markedly reduced infarct size, which was 73±2% of the area at risk in vehicle, 50±4% in DiOHF, 75±5% in control and 44±4% in IPC. Post‐I/R segment shortening within the ischaemic zone was greater in DiOHF (2.3±0.7%; P<0.01) and IPC (1.7±0.5%; P<0.01) than those in corresponding controls (−1.7±0.4; −2.1±0.4%).
DiOHF and IPC improved coronary blood flow to the ischaemic area and preserved higher levels of nitric oxide metabolites in the venous outflow from the ischaemic zone.
DiOHF attenuated superoxide production in post‐I/R myocardium, and significantly reduced infarct size and injury following I/R in anaesthetized sheep. The extent of protection by DiOHF is comparable to that afforded by IPC. Thus, DiOHF has clinical potential for improving recovery from acute myocardial infarction and other ischaemic syndromes.
British Journal of Pharmacology (2004) 142, 443–452. doi:10.1038/sj.bjp.0705815</description><identifier>ISSN: 0007-1188</identifier><identifier>EISSN: 1476-5381</identifier><identifier>DOI: 10.1038/sj.bjp.0705815</identifier><identifier>PMID: 15148246</identifier><identifier>CODEN: BJPCBM</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Animals ; antioxidant ; Antioxidants - administration & dosage ; Antioxidants - therapeutic use ; Biological and medical sciences ; Cardiology. Vascular system ; Coronary Circulation - drug effects ; Coronary heart disease ; Disease Models, Animal ; Flavonoid ; Flavonoids - administration & dosage ; Flavonoids - therapeutic use ; Heart ; ischaemia ; Medical sciences ; Myocardial Contraction - drug effects ; myocardial infarction ; Myocardial Infarction - drug therapy ; Myocardial Infarction - metabolism ; Myocardial Infarction - physiopathology ; Myocardial Reperfusion Injury - metabolism ; Myocardial Reperfusion Injury - physiopathology ; Myocardial Reperfusion Injury - prevention & control ; Myocarditis. Cardiomyopathies ; Myocardium - metabolism ; Neutrophil Infiltration - drug effects ; nitric oxide ; Nitric Oxide - metabolism ; reperfusion ; Sheep ; Superoxides - metabolism ; Time Factors</subject><ispartof>British journal of pharmacology, 2004-06, Vol.142 (3), p.443-452</ispartof><rights>2004 British Pharmacological Society</rights><rights>2004 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Jun 2004</rights><rights>Copyright 2004, Nature Publishing Group 2004 Nature Publishing Group</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4871-4fd1f8fc51533ebf0436fc184e756a13249283397f745542d365a29edb2a58483</citedby><cites>FETCH-LOGICAL-c4871-4fd1f8fc51533ebf0436fc184e756a13249283397f745542d365a29edb2a58483</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1574976/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1574976/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15866333$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15148246$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Sheng</creatorcontrib><creatorcontrib>Dusting, Gregory J</creatorcontrib><creatorcontrib>May, Clive N</creatorcontrib><creatorcontrib>Woodman, Owen L</creatorcontrib><title>3′,4′‐Dihydroxyflavonol reduces infarct size and injury associated with myocardial ischaemia and reperfusion in sheep</title><title>British journal of pharmacology</title><addtitle>Br J Pharmacol</addtitle><description>The antioxidant properties of flavonols in vivo and their potential benefits in myocardial ischaemia/reperfusion (I/R) injury have been little investigated. We evaluated the ability of a synthetic flavonol, 3′,4′‐dihydroxyflavonol (DiOHF) to scavenge superoxide in post‐I/R myocardium and to prevent myocardial I/R injury.
Anaesthetized sheep were studied in four groups (n=5–6): control, ischaemic preconditioning (IPC), vehicle and DiOHF (before reperfusion, 5 mg kg−1, i.v.). The left anterior descending coronary artery was occluded distal to the second diagonal branch for 1 h followed by 2 h of reperfusion. Infarct size, myocardial function, NADPH‐activated superoxide generation and biochemical markers of injury were measured.
DiOHF (10−8–10−4 M) incubated in vitro with post‐I/R myocardium from the vehicle group suppressed superoxide production dose‐dependently. DiOHF administered in vivo also significantly reduced superoxide generation in vitro.
DiOHF and IPC markedly reduced infarct size, which was 73±2% of the area at risk in vehicle, 50±4% in DiOHF, 75±5% in control and 44±4% in IPC. Post‐I/R segment shortening within the ischaemic zone was greater in DiOHF (2.3±0.7%; P<0.01) and IPC (1.7±0.5%; P<0.01) than those in corresponding controls (−1.7±0.4; −2.1±0.4%).
DiOHF and IPC improved coronary blood flow to the ischaemic area and preserved higher levels of nitric oxide metabolites in the venous outflow from the ischaemic zone.
DiOHF attenuated superoxide production in post‐I/R myocardium, and significantly reduced infarct size and injury following I/R in anaesthetized sheep. The extent of protection by DiOHF is comparable to that afforded by IPC. Thus, DiOHF has clinical potential for improving recovery from acute myocardial infarction and other ischaemic syndromes.
British Journal of Pharmacology (2004) 142, 443–452. doi:10.1038/sj.bjp.0705815</description><subject>Animals</subject><subject>antioxidant</subject><subject>Antioxidants - administration & dosage</subject><subject>Antioxidants - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Cardiology. Vascular system</subject><subject>Coronary Circulation - drug effects</subject><subject>Coronary heart disease</subject><subject>Disease Models, Animal</subject><subject>Flavonoid</subject><subject>Flavonoids - administration & dosage</subject><subject>Flavonoids - therapeutic use</subject><subject>Heart</subject><subject>ischaemia</subject><subject>Medical sciences</subject><subject>Myocardial Contraction - drug effects</subject><subject>myocardial infarction</subject><subject>Myocardial Infarction - drug therapy</subject><subject>Myocardial Infarction - metabolism</subject><subject>Myocardial Infarction - physiopathology</subject><subject>Myocardial Reperfusion Injury - metabolism</subject><subject>Myocardial Reperfusion Injury - physiopathology</subject><subject>Myocardial Reperfusion Injury - prevention & control</subject><subject>Myocarditis. Cardiomyopathies</subject><subject>Myocardium - metabolism</subject><subject>Neutrophil Infiltration - drug effects</subject><subject>nitric oxide</subject><subject>Nitric Oxide - metabolism</subject><subject>reperfusion</subject><subject>Sheep</subject><subject>Superoxides - metabolism</subject><subject>Time Factors</subject><issn>0007-1188</issn><issn>1476-5381</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><recordid>eNqFkc9u1DAQxi0EosvClSOKkOBEFju2Y-dSCcqfIlWCA5wtrzMmjpI42ElL4NJH4Fl4pD4Jho2gcMGHseT5zeeZ-RC6T_COYCqfxna3b8cdFphLwm-gDWGizDmV5CbaYIxFToiUR-hOjC3GKSn4bXREOGGyYOUGfaVXl9-fsBSuLr-9cM1SB_95sZ0-94PvsgD1bCBmbrA6mCmL7gtkeqjTQzuHJdMxeuP0BHV24aYm6xdvdKid7jIXTaOhd_oXH2CEYOfo_JBqs9gAjHfRLau7CPfWe4s-vHr5_uQ0P3v7-s3Js7PcMClIzmxNrLSGE04p7C1mtLSGSAaCl5rQglWFpLQSVjDOWVHTkuuignpfaC6ZpFt0fNAd530PtYFhCrpTY3C9Dovy2qm_M4Nr1Ed_rggXrBJlEni8CgT_aYY4qT5NB12nB_BzVKI4rDaBD_8BWz-HIQ2nCiJIVfAKJ2h3gEzwMQawvzshWP00VcVWJVPVamoqeHC9_z_46mICHq2AjkZ3NujBuHiNk2VJ09kieuAuXAfLf75Vz9-dFhQT-gPSE8Ap</recordid><startdate>200406</startdate><enddate>200406</enddate><creator>Wang, Sheng</creator><creator>Dusting, Gregory J</creator><creator>May, Clive N</creator><creator>Woodman, Owen L</creator><general>Blackwell Publishing Ltd</general><general>Nature Publishing</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>7QP</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</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>200406</creationdate><title>3′,4′‐Dihydroxyflavonol reduces infarct size and injury associated with myocardial ischaemia and reperfusion in sheep</title><author>Wang, Sheng ; Dusting, Gregory J ; May, Clive N ; Woodman, Owen L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4871-4fd1f8fc51533ebf0436fc184e756a13249283397f745542d365a29edb2a58483</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>antioxidant</topic><topic>Antioxidants - administration & dosage</topic><topic>Antioxidants - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Cardiology. Vascular system</topic><topic>Coronary Circulation - drug effects</topic><topic>Coronary heart disease</topic><topic>Disease Models, Animal</topic><topic>Flavonoid</topic><topic>Flavonoids - administration & dosage</topic><topic>Flavonoids - therapeutic use</topic><topic>Heart</topic><topic>ischaemia</topic><topic>Medical sciences</topic><topic>Myocardial Contraction - drug effects</topic><topic>myocardial infarction</topic><topic>Myocardial Infarction - drug therapy</topic><topic>Myocardial Infarction - metabolism</topic><topic>Myocardial Infarction - physiopathology</topic><topic>Myocardial Reperfusion Injury - metabolism</topic><topic>Myocardial Reperfusion Injury - physiopathology</topic><topic>Myocardial Reperfusion Injury - prevention & control</topic><topic>Myocarditis. Cardiomyopathies</topic><topic>Myocardium - metabolism</topic><topic>Neutrophil Infiltration - drug effects</topic><topic>nitric oxide</topic><topic>Nitric Oxide - metabolism</topic><topic>reperfusion</topic><topic>Sheep</topic><topic>Superoxides - metabolism</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Sheng</creatorcontrib><creatorcontrib>Dusting, Gregory J</creatorcontrib><creatorcontrib>May, Clive N</creatorcontrib><creatorcontrib>Woodman, Owen L</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>Calcium & Calcified Tissue Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</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>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</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)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Biological Science Journals</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>British journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Sheng</au><au>Dusting, Gregory J</au><au>May, Clive N</au><au>Woodman, Owen L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>3′,4′‐Dihydroxyflavonol reduces infarct size and injury associated with myocardial ischaemia and reperfusion in sheep</atitle><jtitle>British journal of pharmacology</jtitle><addtitle>Br J Pharmacol</addtitle><date>2004-06</date><risdate>2004</risdate><volume>142</volume><issue>3</issue><spage>443</spage><epage>452</epage><pages>443-452</pages><issn>0007-1188</issn><eissn>1476-5381</eissn><coden>BJPCBM</coden><abstract>The antioxidant properties of flavonols in vivo and their potential benefits in myocardial ischaemia/reperfusion (I/R) injury have been little investigated. We evaluated the ability of a synthetic flavonol, 3′,4′‐dihydroxyflavonol (DiOHF) to scavenge superoxide in post‐I/R myocardium and to prevent myocardial I/R injury.
Anaesthetized sheep were studied in four groups (n=5–6): control, ischaemic preconditioning (IPC), vehicle and DiOHF (before reperfusion, 5 mg kg−1, i.v.). The left anterior descending coronary artery was occluded distal to the second diagonal branch for 1 h followed by 2 h of reperfusion. Infarct size, myocardial function, NADPH‐activated superoxide generation and biochemical markers of injury were measured.
DiOHF (10−8–10−4 M) incubated in vitro with post‐I/R myocardium from the vehicle group suppressed superoxide production dose‐dependently. DiOHF administered in vivo also significantly reduced superoxide generation in vitro.
DiOHF and IPC markedly reduced infarct size, which was 73±2% of the area at risk in vehicle, 50±4% in DiOHF, 75±5% in control and 44±4% in IPC. Post‐I/R segment shortening within the ischaemic zone was greater in DiOHF (2.3±0.7%; P<0.01) and IPC (1.7±0.5%; P<0.01) than those in corresponding controls (−1.7±0.4; −2.1±0.4%).
DiOHF and IPC improved coronary blood flow to the ischaemic area and preserved higher levels of nitric oxide metabolites in the venous outflow from the ischaemic zone.
DiOHF attenuated superoxide production in post‐I/R myocardium, and significantly reduced infarct size and injury following I/R in anaesthetized sheep. The extent of protection by DiOHF is comparable to that afforded by IPC. Thus, DiOHF has clinical potential for improving recovery from acute myocardial infarction and other ischaemic syndromes.
British Journal of Pharmacology (2004) 142, 443–452. doi:10.1038/sj.bjp.0705815</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>15148246</pmid><doi>10.1038/sj.bjp.0705815</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | British journal of pharmacology, 2004-06, Vol.142 (3), p.443-452 |
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| subjects | Animals antioxidant Antioxidants - administration & dosage Antioxidants - therapeutic use Biological and medical sciences Cardiology. Vascular system Coronary Circulation - drug effects Coronary heart disease Disease Models, Animal Flavonoid Flavonoids - administration & dosage Flavonoids - therapeutic use Heart ischaemia Medical sciences Myocardial Contraction - drug effects myocardial infarction Myocardial Infarction - drug therapy Myocardial Infarction - metabolism Myocardial Infarction - physiopathology Myocardial Reperfusion Injury - metabolism Myocardial Reperfusion Injury - physiopathology Myocardial Reperfusion Injury - prevention & control Myocarditis. Cardiomyopathies Myocardium - metabolism Neutrophil Infiltration - drug effects nitric oxide Nitric Oxide - metabolism reperfusion Sheep Superoxides - metabolism Time Factors |
| title | 3′,4′‐Dihydroxyflavonol reduces infarct size and injury associated with myocardial ischaemia and reperfusion in sheep |
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