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dc.contributor.authorWillems, Lauraen_US
dc.contributor.authorHeadrick, Johnen_US
dc.date.accessioned2017-04-24T08:09:06Z
dc.date.available2017-04-24T08:09:06Z
dc.date.issued2005en_US
dc.date.modified2009-09-23T02:38:58Z
dc.identifier.issn03051870en_US
dc.identifier.doi10.1111/j.1440-1681.2005.04168.xen_AU
dc.identifier.urihttp://hdl.handle.net/10072/4735
dc.description.abstract1. By selectively modifying adenosine metabolism via adenosine deaminase or adenosine kinase inhibitors, it may be possible to enhance the receptor-mediated protective actions of adenosine in a site- and event-specific fashion. 2. We characterized cardioprotective actions of the adenosine deaminase inhibitor erythro-2-(2-hydroxy-3-non-yl)adenine (EHNA) and the adenosine kinase inhibitor iodotubercidin in C57/Bl6 mouse hearts subjected to 20 min global normothermic ischaemia and 40 min reperfusion. 3. Ventricular pressure development only recovered to 45 ᠲ% of baseline levels (67 ᠵ mmHg) in untreated hearts, with sustained and pronounced diastolic contracture (25 ᠲ mmHg). Treatment with 20 孯l/L EHNA increased recovery of ventricular pressure (107 ᠹ mmHg), reduced postischaemic diastolic pressure (13 ᠱ mmHg) and reduced loss of lactate dehydrogenase (LDH; an indicator of necrotic damage) by 50% (9 ᠲ vs 19 ᠲ IU/g). Adenosine kinase inhibition with 10 孯l/L iodotubercidin also improved pressure development (to 100 ᠸ mmHg) and reduced LDH efflux (5 ᠲ IU/g). 4. Protective actions were mimicked by adenosine and inhibited by adenosine receptor antagonism (50 孯l/L 8-?-sulfophenyltheophylline) and mitochondrial KATP channel inhibition (50 孯l/L 5-hydroxydecanoate). 5. Coinfusion of the inhibitors, 'trapping' formed adenosine, failed to exert protection and, in some instances, was detrimental. Although substantial benefit was gained by these agents in hearts from young animals, neither inhibitor was effective in 'aged' hearts (18 months). 6. Our data demonstrate that adenosine deaminase or kinase inhibition substantially limits injury during ischaemia-reperfusion. Protection involves adenosine receptor activation. However, cardioprotection via either enzyme inhibitor requires an alternative purine-salvage pathway to be functional and was reduced in aged hearts known to be increasingly susceptible to ischaemic damage.en_US
dc.description.peerreviewedYesen_US
dc.description.publicationstatusYesen_AU
dc.languageEnglishen_US
dc.language.isoen_AU
dc.publisherBlackwell Publishing Asiaen_US
dc.publisher.placeAustraliaen_US
dc.relation.ispartofstudentpublicationNen_AU
dc.relation.ispartofpagefrom179en_US
dc.relation.ispartofpageto183en_US
dc.relation.ispartofissue3en_US
dc.relation.ispartofjournalClinical and Experimental Pharmacology & Physiologyen_US
dc.relation.ispartofvolume32en_US
dc.rights.retentionYen_AU
dc.subject.fieldofresearchcode320502en_US
dc.titleProtecting murine hearts from ischaemia-reperfusion using selective inhibitors of adenosine metabolismen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.rights.copyrightCopyright 2005 Blackwell Publishing. The definitive version is available at [www.blackwell-synergy.com.]en_AU
gro.date.issued2005
gro.hasfulltextNo Full Text


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