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

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 293; no. 4; p. H2557
• Main Authors: Sato, Hiroshi, Bolli, Roberto, Rokosh, Gregg D, Bi, Qiuli, Dai, Shujing, Shirk, Gregg, Tang, Xian-Liang
• Format: Journal Article
• Language: English
• Published: United States 01-10-2007
• 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
• ISSN: 0363-6135
• DOI: 10.1152/ajpheart.00858.2007

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.