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Influence of fatty acids on cardioprotection by preischaemic inhibition of the malate-aspartate shuttle.
MedLine Citation:
PMID:  22831462     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The malate-aspartate shuttle (MAS) is the main pathway for balancing extra- and intramitochondrial glucose metabolism. Preischaemic shutdown of the MAS by aminooxyacetate (AOA) mimics ischaemic preconditioning (IPC) in glucose perfused rat hearts. We aimed to determine the influence of fatty acids (FA) on cardioprotection by preischaemic inhibition of the MAS. Isolated rat hearts were perfused with 11 mM glucose, 3% bovine serum albumin plus 0, 0.4 or 1.2 mM FA and compared in a) control, b) preischaemic AOA (0.2 mM), c) IPC and d) AOA+IPC. The perfusion protocol included 30 min global no-flow ischaemia and 120 min reperfusion. Infarct size (IS), haemodynamic recovery, glucose oxidation and lactate release were evaluated. AOA reduced IS of the left ventricle in hearts perfused with 0, 0.4 and 1.2 mM FA vs. control hearts (26±2 vs. 53±4, 29±3 vs. 53±4, and 61±4 vs. 81±3% respectively, p<0.01 for all). After 2 hours of reperfusion AOA improved haemodynamic recovery in the absence (52±2 vs. 27±3 mmHg, p<0.001) but not in the presence of FA. IPC and AOA+IPC reduced IS and improved haemodynamic recovery irrespective of FA levels. Postischaemic glucose oxidation was suppressed by FA and did not significantly differ between intervention groups. We conclude that infarct reduction induced by preischaemic MAS shutdown is not compromised by physiological FA concentrations. Transient MAS shutdown may be involved but is not a sufficient underlying mechanism behind IPC. © 2012 The Authors Clinical and Experimental Pharmacology and Physiology © 2012 Blackwell Publishing Asia Pty Ltd.
Authors:
Christian Dalgas; Jonas Agerlund Povlsen; Bo Løfgren; Sune Brinck Erichsen; Hans Erik Bøtker
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-25
Journal Detail:
Title:  Clinical and experimental pharmacology & physiology     Volume:  -     ISSN:  1440-1681     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-26     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0425076     Medline TA:  Clin Exp Pharmacol Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 The Authors Clinical and Experimental Pharmacology and Physiology © 2012 Blackwell Publishing Asia Pty Ltd.
Affiliation:
Department of Cardiology, Aarhus University Hospital Skejby, Brendstrupgaardsvej 100, DK-8200, Aarhus N, Denmark; Institute of Clinical Medicine, Aarhus University, Brendstrupgaardsvej 100, DK-8200, Aarhus N, Denmark.
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