The cardioprotection of the late phase of ischemic preconditioning is enhanced by postconditioning via a COX-2-mediated mechanism in conscious rats
Autor: | Roberto Bolli, Hiroshi Sato, Qiuli Bi, Gregg Rokosh, Xian Liang Tang, Shujing Dai, Gregg Shirk |
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Rok vydání: | 2007 |
Předmět: |
Male
Time Factors Consciousness Physiology Ischemia Myocardial Infarction Myocardial Reperfusion Injury Pharmacology Dinoprostone Article Late phase Physiology (medical) medicine Animals Ischemic Preconditioning Cardioprotection Sulfonamides Cyclooxygenase 2 Inhibitors business.industry Myocardium medicine.disease Infarct size Rats Inbred F344 Rats Up-Regulation Disease Models Animal Celecoxib Cyclooxygenase 2 Anesthesia Circulatory system Ischemic preconditioning Pyrazoles Cardiology and Cardiovascular Medicine business |
Zdroj: | American journal of physiology. Heart and circulatory physiology. 293(4) |
ISSN: | 0363-6135 |
Popis: | 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 PGE2) 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 PGE2 content. PGE2 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. |
Databáze: | OpenAIRE |
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