Cardioprotection with adenosine metabolism inhibitors in ischemic-reperfused mouse heart

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Title Cardioprotection with adenosine metabolism inhibitors in ischemic-reperfused mouse heart
Author Peart, Jason Nigel John; Matherne, Paul; Cerniway, Rachel; Headrick, John Patrick
Journal Name Cardiovascular Research
Year Published 2001
Place of publication Netherlands
Publisher Elsevier Science
Abstract Objectives: To characterize the anti-ischemic' effects of adenosine metabolism inhibition in ischemicreperfused 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 ¼M erythro-2-(2-hydroxy-3-nonyl)adenine; EHNA) adenosine kinase inhibition (10 ¼M iodotubercidin; IODO), or 10 ¼M adenosine. Hearts overexpressing A1 adenosine receptors (A1ARs) were also studied. Results: EHNA treatment reduced ischemic contracture and post-ischemic diastolic pressure (14±2 vs. 20±1 mmHg), increased recovery of developed pressure (66±3 vs. 53±2%) and reduced LDH efflux (8.9±1.6 vs. 18.0±1.7 I.U./g). IODO also improved functional recovery (to 60±2%) and reduced LDH efflux (5.3±1.7 I.U./g), as did treatment with 10 ¼M adenosine. Protection with EHNA was reversed by co-infusion of IODO or 50 ¼M 8-Á-sulfophenyltheophylline (adenosine receptor antagonist), but unaltered by 20 ¼M inosine+10 ¼m hypoxanthine. Similarly, effects of iodotubercidin were inhibited by EHNA and 8-Á-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 ischemiareperfusion. 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.
Peer Reviewed Yes
Published Yes
Publisher URI
Copyright Statement Copyright 2001 Elsevier : Reproduced in accordance with the copyright policy of the publisher : This journal is available online - use hypertext links.
Volume 52
Page from 120
Page to 129
ISSN 0008-6363
Date Accessioned 2002-04-16
Language en_AU
Research Centre Heart Foundation Research Centre; Menzies Health Institute Qld
Subject Cardiology (incl. Cardiovascular Diseases)
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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