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dc.contributor.authorWillems, Lauraen_US
dc.contributor.authorGarnham, Bronwynen_US
dc.contributor.authorHeadrick, Johnen_US
dc.date.accessioned2017-04-24T08:09:02Z
dc.date.available2017-04-24T08:09:02Z
dc.date.issued2003en_US
dc.date.modified2007-03-15T21:37:10Z
dc.identifier.issn05315565en_US
dc.identifier.urihttp://hdl.handle.net/10072/6140
dc.description.abstractImpaired tolerance to ischemia-reperfusion in older hearts may stem in part from alterations in purine catabolism, impacting on maintenance of energy state and protective signaling via extracellular adenosine. We characterized effects of aging on normoxic and post-ischemic purine metabolism in hearts from young (2-4 month), middle-aged (12 month), old (18 month), and senescent (24-28 month) C57/Bl6 mice. Normoxic function was similar in all age groups while normoxic purine efflux increased gradually with age. This was the result of enhanced efflux of hypoxanthine, xanthine and uric acid, with extracellular accumulation of adenosine and inosine remaining unchanged. While total purine washout during 60 min reperfusion following 20 min global ischemia was unaltered by aging (1057ᱰ9 nmoles/g in young vs. 1221ᱲ7 nmoles/g in senescent hearts), selective changes in purine catabolism were evident. Accumulation of adenosine and inosine were reduced by 50 and 80%, respectively, matched by 400 and 300% elevations in hypoxanthine and xanthine accumulation, respectively. Uric acid remained unchanged. Thus, while adenosine and inosine represented 15Რand 47᳥ of total purine efflux in young hearts, these values decreased to only 6ᱠand 9Ქ in senescent hearts. Efflux of IMP also increased 500% with aging whereas 5'-AMP was unaltered. These changes were associated with a substantial fall in ischemic tolerance, with left ventricular developed pressure recovering to 46᳥ in young hearts vs. only 24ᶬ 16ᴬ and 19ᴥ in middle-age, old and senescent hearts, respectively. Our data collectively support a pronounced shift in purine catabolism, with reduced accumulation of salvageable and cardioprotective adenosine, and enhanced accumulation of poorly salvaged (and potentially injurious) hypoxanthine and xanthine. Mechanisms underlying this shift have yet to be determined. However, this may play a role in the marked decline in myocardial tolerance to ischemia with aging and senescence.en_US
dc.description.peerreviewedYesen_US
dc.description.publicationstatusYesen_AU
dc.languageEnglishen_US
dc.language.isoen_AU
dc.publisherElsevier Inc.en_US
dc.publisher.placeUKen_US
dc.publisher.urihttp://www.elsevier.com/wps/find/journaldescription.cws_home/525468/description#descriptionen_AU
dc.relation.ispartofpagefrom1169en_US
dc.relation.ispartofpageto1177en_US
dc.relation.ispartofjournalEXPERIMENTAL GERONTOLOGYen_US
dc.relation.ispartofvolume38en_US
dc.subject.fieldofresearchcode320699en_US
dc.titleAging-related changes in myocardial purine metabolism and ischemic toleranceen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.rights.copyrightCopyright 2003 Elsevier : Reproduced in accordance with the copyright policy of the publisher : This journal is available online - use hypertext links.en_AU
gro.date.issued2003
gro.hasfulltextNo Full Text


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