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dc.contributor.authorWillems, L
dc.contributor.authorHeadrick, JP
dc.date.accessioned2017-05-03T11:16:41Z
dc.date.available2017-05-03T11:16:41Z
dc.date.issued2005
dc.date.modified2009-09-23T02:38:58Z
dc.identifier.issn0305-1870
dc.identifier.doi10.1111/j.1440-1681.2005.04168.x
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.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherBlackwell Publishing Asia
dc.publisher.placeAustralia
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom179
dc.relation.ispartofpageto183
dc.relation.ispartofissue3
dc.relation.ispartofjournalClinical and Experimental Pharmacology & Physiology
dc.relation.ispartofvolume32
dc.rights.retentionY
dc.subject.fieldofresearchZoology
dc.subject.fieldofresearchPharmacology and pharmaceutical sciences
dc.subject.fieldofresearchMedical physiology
dc.subject.fieldofresearchClinical sciences
dc.subject.fieldofresearchcode3109
dc.subject.fieldofresearchcode3214
dc.subject.fieldofresearchcode3208
dc.subject.fieldofresearchcode3202
dc.titleProtecting murine hearts from ischaemia-reperfusion using selective inhibitors of adenosine metabolism
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.rights.copyright© 2005 Blackwell Publishing. The definitive version is available at [www.blackwell-synergy.com.]
gro.date.issued2005
gro.hasfulltextNo Full Text
gro.griffith.authorHeadrick, John P.


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