Pyruvate-dependent preconditioning and cardioprotection in murine myocardium

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Title Pyruvate-dependent preconditioning and cardioprotection in murine myocardium
Author Zatta, Amanda Jane; Hack, Benjamin Daniel Noel; Headrick, John Patrick
Journal Name Clinical and Experimental Pharmacology & Physiology
Year Published 2003
Place of publication Australia
Publisher Blackwell Publishing Asia
Abstract 1. Whether pyruvate inhibits or can actually initiate myocardial preconditioning is unclear and whether pyruvate provides protection via its action as a 'cosubstrate' with glucose or via alternative mechanisms also remains controversial. We examined effects of a high concentration of pyruvate (10 mmol/L) alone or with 15 mmol/L glucose in mouse hearts subjected to 20 min ischaemia and 30 min reperfusion. 2. Provision of 10 mmol/L pyruvate alone or as a cosubstrate markedly reduced ischaemic contracture and enhanced postischaemic recovery. Time to contracture was increased from approximately 3 min to over 8 min, peak contracture was reduced from 90 mmHg to less than 60 mmHg and postischaemic pressure development was also improved. Effects on contracture were independent of the presence of pyruvate during ischaemia and improved postischaemic recovery was evident with pre-ischaemic pyruvate perfusion. 3. Cardioprotection did not require the presence of pyruvate during ischaemia or reperfusion and effects of pyruvate pretreatment could be mimicked by pretreatment with 1 mmol/L dichloroacetate (DCA), an activator of pyruvate dehydrogenase. 4. Myocardial adenosine efflux and Ca2+ content were elevated (by 215 and 65%, respectively) following pretreatment with pyruvate, potentially triggering a preconditioned state. A role for adenosine A1 receptors is supported by lack of added protection with pyruvate in hearts transgenically overexpressing adenosine A1 receptors. 5. Collectively, these observations demonstrate that pre-ischaemic treatment with pyruvate or DCA provides a beneficial preconditioning-like effect in ischaemic and postischaemic myocardium. The response appears unrelated to glycolytic inhibition, but may be mediated via transient changes in adenosine levels and/or cellular Ca2+.
Peer Reviewed Yes
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Copyright Statement Copyright 2003 Blackwell Publishing. The definitive version is available at []
Volume 30
Page from 145
Page to 152
ISSN 0305-1870
Date Accessioned 2004-04-07
Language en_AU
Research Centre Heart Foundation Research Centre; Menzies Health Institute Qld
Faculty Griffith Health Faculty
Subject Medical Physiology
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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