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The cardioprotection of the late phase of ischemic preconditioning is enhanced by postconditioning via a COX-2-mediated mechanism in conscious rats

Institute of Molecular Cardiology, Department of Medicine, University of Louisville, Louisville, Kentucky Submitted 23 July 2007 ; accepted in final form 16 August 2007 The present study sought to determine whether the combination of late preconditioning (PC) with postconditioning enhances the reduc...

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Published in:American journal of physiology. Heart and circulatory physiology 2007-10, Vol.293 (4), p.H2557-H2564
Main Authors: Sato, Hiroshi, Bolli, Roberto, Rokosh, Gregg D, Bi, Qiuli, Dai, Shujing, Shirk, Gregg, Tang, Xian-Liang
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description Institute of Molecular Cardiology, Department of Medicine, University of Louisville, Louisville, Kentucky Submitted 23 July 2007 ; accepted in final form 16 August 2007 The present study sought to determine whether the combination of late preconditioning (PC) with postconditioning enhances the reduction in infarct size. Chronically instrumented rats were assigned to a 45-min ( subset 1 ) or 60-min ( subset 2 ) coronary occlusion followed by 24 h of reperfusion. In each subset, rats received no further intervention (control) or were preconditioned 24 h before occlusion (PC), postconditioned at the onset of reperfusion following occlusion, or preconditioned and postconditioned without (PC + postconditioning) or with the COX-2 inhibitor celecoxib (3 mg/kg ip; PC + postconditioning + celecoxib) 10 min before postconditioning. Myocardial cyclooxygenase-2 (COX-2) protein expression and COX-2 activity (assessed as myocardial levels of PGE 2 ) were measured 6 min after reperfusion in an additional five groups (control, PC, postconditioning, PC + postconditioning, and PC + postconditioning + celecoxib) subjected to a 45-min occlusion. PC alone reduced infarct size after a 45-min occlusion but not after a 60-min occlusion. Postconditioning alone did not reduce infarct size in either setting. However, the combination of late PC and postconditioning resulted in a robust infarct-sparing effect in both settings, suggesting additive cardioprotection. Celecoxib completely abrogated the infarct-sparing effect of the combined interventions in both settings. Late PC increased COX-2 protein expression and PGE 2 content. PGE 2 content (but not COX-2 protein) was further increased by the combination of both interventions, suggesting that postconditioning increases the activity of COX-2 induced by late PC. In conclusion, the combination of late PC and postconditioning produces additive protection, likely due to a postconditioning-induced enhancement of COX-2 activity. myocardium; ischemia; infarct size; cyclooxygenase-2 Address for reprint requests and other correspondence: X.-L. Tang, Institute of Molecular Cardiology, Univ. of Louisville, Louisville, KY 40202 (e-mail: xltang{at}louisville.edu )
doi_str_mv 10.1152/ajpheart.00858.2007
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Chronically instrumented rats were assigned to a 45-min ( subset 1 ) or 60-min ( subset 2 ) coronary occlusion followed by 24 h of reperfusion. In each subset, rats received no further intervention (control) or were preconditioned 24 h before occlusion (PC), postconditioned at the onset of reperfusion following occlusion, or preconditioned and postconditioned without (PC + postconditioning) or with the COX-2 inhibitor celecoxib (3 mg/kg ip; PC + postconditioning + celecoxib) 10 min before postconditioning. Myocardial cyclooxygenase-2 (COX-2) protein expression and COX-2 activity (assessed as myocardial levels of PGE 2 ) were measured 6 min after reperfusion in an additional five groups (control, PC, postconditioning, PC + postconditioning, and PC + postconditioning + celecoxib) subjected to a 45-min occlusion. PC alone reduced infarct size after a 45-min occlusion but not after a 60-min occlusion. Postconditioning alone did not reduce infarct size in either setting. However, the combination of late PC and postconditioning resulted in a robust infarct-sparing effect in both settings, suggesting additive cardioprotection. Celecoxib completely abrogated the infarct-sparing effect of the combined interventions in both settings. Late PC increased COX-2 protein expression and PGE 2 content. PGE 2 content (but not COX-2 protein) was further increased by the combination of both interventions, suggesting that postconditioning increases the activity of COX-2 induced by late PC. In conclusion, the combination of late PC and postconditioning produces additive protection, likely due to a postconditioning-induced enhancement of COX-2 activity. myocardium; ischemia; infarct size; cyclooxygenase-2 Address for reprint requests and other correspondence: X.-L. 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Heart and circulatory physiology</title><addtitle>Am J Physiol Heart Circ Physiol</addtitle><description>Institute of Molecular Cardiology, Department of Medicine, University of Louisville, Louisville, Kentucky Submitted 23 July 2007 ; accepted in final form 16 August 2007 The present study sought to determine whether the combination of late preconditioning (PC) with postconditioning enhances the reduction in infarct size. Chronically instrumented rats were assigned to a 45-min ( subset 1 ) or 60-min ( subset 2 ) coronary occlusion followed by 24 h of reperfusion. In each subset, rats received no further intervention (control) or were preconditioned 24 h before occlusion (PC), postconditioned at the onset of reperfusion following occlusion, or preconditioned and postconditioned without (PC + postconditioning) or with the COX-2 inhibitor celecoxib (3 mg/kg ip; PC + postconditioning + celecoxib) 10 min before postconditioning. Myocardial cyclooxygenase-2 (COX-2) protein expression and COX-2 activity (assessed as myocardial levels of PGE 2 ) were measured 6 min after reperfusion in an additional five groups (control, PC, postconditioning, PC + postconditioning, and PC + postconditioning + celecoxib) subjected to a 45-min occlusion. PC alone reduced infarct size after a 45-min occlusion but not after a 60-min occlusion. Postconditioning alone did not reduce infarct size in either setting. However, the combination of late PC and postconditioning resulted in a robust infarct-sparing effect in both settings, suggesting additive cardioprotection. Celecoxib completely abrogated the infarct-sparing effect of the combined interventions in both settings. Late PC increased COX-2 protein expression and PGE 2 content. PGE 2 content (but not COX-2 protein) was further increased by the combination of both interventions, suggesting that postconditioning increases the activity of COX-2 induced by late PC. 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Heart and circulatory physiology</jtitle><addtitle>Am J Physiol Heart Circ Physiol</addtitle><date>2007-10-01</date><risdate>2007</risdate><volume>293</volume><issue>4</issue><spage>H2557</spage><epage>H2564</epage><pages>H2557-H2564</pages><issn>0363-6135</issn><eissn>1522-1539</eissn><abstract>Institute of Molecular Cardiology, Department of Medicine, University of Louisville, Louisville, Kentucky Submitted 23 July 2007 ; accepted in final form 16 August 2007 The present study sought to determine whether the combination of late preconditioning (PC) with postconditioning enhances the reduction in infarct size. Chronically instrumented rats were assigned to a 45-min ( subset 1 ) or 60-min ( subset 2 ) coronary occlusion followed by 24 h of reperfusion. In each subset, rats received no further intervention (control) or were preconditioned 24 h before occlusion (PC), postconditioned at the onset of reperfusion following occlusion, or preconditioned and postconditioned without (PC + postconditioning) or with the COX-2 inhibitor celecoxib (3 mg/kg ip; PC + postconditioning + celecoxib) 10 min before postconditioning. Myocardial cyclooxygenase-2 (COX-2) protein expression and COX-2 activity (assessed as myocardial levels of PGE 2 ) were measured 6 min after reperfusion in an additional five groups (control, PC, postconditioning, PC + postconditioning, and PC + postconditioning + celecoxib) subjected to a 45-min occlusion. PC alone reduced infarct size after a 45-min occlusion but not after a 60-min occlusion. Postconditioning alone did not reduce infarct size in either setting. However, the combination of late PC and postconditioning resulted in a robust infarct-sparing effect in both settings, suggesting additive cardioprotection. Celecoxib completely abrogated the infarct-sparing effect of the combined interventions in both settings. Late PC increased COX-2 protein expression and PGE 2 content. PGE 2 content (but not COX-2 protein) was further increased by the combination of both interventions, suggesting that postconditioning increases the activity of COX-2 induced by late PC. In conclusion, the combination of late PC and postconditioning produces additive protection, likely due to a postconditioning-induced enhancement of COX-2 activity. myocardium; ischemia; infarct size; cyclooxygenase-2 Address for reprint requests and other correspondence: X.-L. Tang, Institute of Molecular Cardiology, Univ. of Louisville, Louisville, KY 40202 (e-mail: xltang{at}louisville.edu )</abstract><cop>United States</cop><pmid>17704286</pmid><doi>10.1152/ajpheart.00858.2007</doi><oa>free_for_read</oa></addata></record>
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identifier ISSN: 0363-6135
ispartof American journal of physiology. Heart and circulatory physiology, 2007-10, Vol.293 (4), p.H2557-H2564
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source American Physiological Society Free
subjects Animals
Celecoxib
Consciousness
Cyclooxygenase 2 - metabolism
Cyclooxygenase 2 Inhibitors - pharmacology
Cyclooxygenase 2 Inhibitors - therapeutic use
Dinoprostone - metabolism
Disease Models, Animal
Ischemic Preconditioning - methods
Male
Myocardial Infarction - enzymology
Myocardial Infarction - metabolism
Myocardial Infarction - prevention & control
Myocardial Reperfusion Injury - enzymology
Myocardial Reperfusion Injury - metabolism
Myocardial Reperfusion Injury - prevention & control
Myocardium - enzymology
Myocardium - metabolism
Myocardium - pathology
Pyrazoles - pharmacology
Pyrazoles - therapeutic use
Rats
Rats, Inbred F344
Sulfonamides - pharmacology
Sulfonamides - therapeutic use
Time Factors
Up-Regulation
title The cardioprotection of the late phase of ischemic preconditioning is enhanced by postconditioning via a COX-2-mediated mechanism in conscious rats
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