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dc.contributor.authorPeart, J
dc.contributor.authorMatherne, GP
dc.contributor.authorCerniway, RJ
dc.contributor.authorHeadrick, JP
dc.description.abstractObjectives: To characterize the 'anti-ischemic' effects of adenosine metabolism inhibition in ischemic-reperfused myocardium. Methods: Perfused C57/B16 mouse hearts were subjected to 20 min ischemia 40 min reperfusion in the absence or presence of adenosine deaminase inhibition (50 占erythro-2-(2-hydroxy-3-nonyl)adenine; EHNA) adenosine kinase inhibition (10 占iodotubercidin; IODO), or 10 占adenosine. Hearts overexpressing A1 adenosine receptors (A1ARs) were also studied. Results: EHNA treatment reduced ischemic contracture and post-ischemic diastolic pressure (14Რvs. 20ᱠmmHg), increased recovery of developed pressure (66᳠vs. 53Ქ) and reduced LDH efflux (8.9ᱮ6 vs. 18.0ᱮ7 I.U./g). IODO also improved functional recovery (to 60Ქ) and reduced LDH efflux (5.3ᱮ7 I.U./g), as did treatment with 10 占adenosine. Protection with EHNA was reversed by co-infusion of IODO or 50 占8-?-sulfophenyltheophylline (adenosine receptor antagonist), but unaltered by 20 占inosine+10 孠hypoxanthine. Similarly, effects of iodotubercidin were inhibited by EHNA and 8-?-sulfophenyltheophylline. A1AR overexpression exerted similar effects to EHNA and EHNA or IODO alone enhanced recovery while EHNA+IODO reduced recovery in transgenic hearts. Functional recoveries and xanthine oxidase reactant levels were unrelated in the groups studied. Conclusions: Adenosine deaminase or kinase inhibition protects from ischemia-reperfusion. Cardioprotection via these enzyme inhibitors requires a functioning purine salvage pathway and involves enhanced adenosine receptor activation. Reduced formation of inosine is unimportant in EHNA-mediated protection.
dc.publisherElsevier Science
dc.relation.ispartofjournalCardiovascular Research
dc.subject.fieldofresearchCardiovascular medicine and haematology
dc.titleCardioprotection with adenosine metabolism inhibitors in ischemic-reperfused mouse heart
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.facultyGriffith Health, School of Medical Science
gro.rights.copyright© 2001 Elsevier : Reproduced in accordance with the copyright policy of the publisher : This journal is available online - use hypertext links.
gro.hasfulltextNo Full Text
gro.griffith.authorHeadrick, John P.
gro.griffith.authorPeart, Jason N.

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