title: The cardioprotection of the late phase of ischemic preconditioning is enhanced by postconditioning via a COX-2-mediated mechanism in conscious rats.
abstract: 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.
authors: Institute of Molecular Cardiology, Department of Medicine, University of Louisville, Louisville, Kentucky 40202, USA.
authors: Hiroshi
authors: H
authors: Sato
authors: Roberto
authors: R
authors: Bolli
authors: Gregg D
authors: GD
authors: Rokosh
authors: Qiuli
authors: Q
authors: Bi
authors: Shujing
authors: S
authors: Dai
authors: Gregg
authors: G
authors: Shirk
authors: Xian-Liang
authors: XL
authors: Tang
mesh_terms: D000818:Animals; D000068579:Celecoxib; D003243:Consciousness; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D019194:Ischemic Preconditioning / Q000379:methods; D008297:Male; D009203:Myocardial Infarction / Q000201:enzymology / Q000378:metabolism / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000378:metabolism / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D011720:Pyrazoles / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011916:Rats, Inbred F344; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D000068579:Celecoxib; D015232:Dinoprostone
references: Cardiovasc Res. 2004 Oct 1;64(1):61-71
references: 15364614
references: J Am Coll Cardiol. 2003 Apr 2;41(7):1183-94
references: 12679220
references: Circulation. 2005 Jan 18;111(2):194-7
references: 15642769
references: Circ Res. 1997 Dec;81(6):1094-107
references: 9400391
references: Cardiovasc Res. 2006 May 1;70(2):315-24
references: 16443207
references: Am J Physiol Heart Circ Physiol. 2006 Nov;291(5):H2308-17
references: 16815986
references: J Am Coll Cardiol. 2003 Apr 2;41(7):1195-7
references: 12679221
references: Basic Res Cardiol. 2005 Jan;100(1):57-63
references: 15614590
references: Anesthesiology. 2004 Mar;100(3):547-54
references: 15108967
references: J Am Coll Cardiol. 2004 Sep 1;44(5):1103-10
references: 15337225
references: Circulation. 1998 Aug 4;98(5):441-9
references: 9714095
references: Basic Res Cardiol. 2005 Jul;100(4):295-310
references: 15793629
references: Proc Natl Acad Sci U S A. 2000 Aug 29;97(18):10197-202
references: 10963682
references: Life Sci. 2006 Apr 25;78(22):2543-9
references: 16325209
references: Trends Cardiovasc Med. 2005 Feb;15(2):69-75
references: 15885573
references: Basic Res Cardiol. 1996 Jan-Feb;91(1):1-4
references: 8660246
references: Life Sci. 2004 May 28;75(2):129-40
references: 15120566
references: Am J Physiol Heart Circ Physiol. 2005 Oct;289(4):H1618-26
references: 15937101
references: Cardiovasc Res. 2002 Aug 15;55(3):495-505
references: 12160946
references: Am J Physiol Heart Circ Physiol. 2007 Jan;292(1):H19-27
references: 16963615
references: Circ Res. 2004 Aug 6;95(3):230-2
references: 15242972
references: Expert Rev Cardiovasc Ther. 2005 Nov;3(6):1035-45
references: 16292995
references: Am J Physiol Heart Circ Physiol. 2003 Aug;285(2):H579-88
references: 12860564
references: Basic Res Cardiol. 2000 Dec;95(6):479-84
references: 11192369
references: Basic Res Cardiol. 2006 Nov;101(6):502-7
references: 16830072
references: Cardiovasc Res. 2005 Jul 1;67(1):124-33
references: 15949476
references: Am J Physiol Heart Circ Physiol. 2006 May;290(5):H1960-8
references: 16339820
references: Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11693-7
references: 8265610
references: Anesthesiology. 2004 Mar;100(3):525-31
references: 15108964
references: Anesthesiology. 2005 Jan;102(1):102-9
references: 15618793
references: Circ Res. 2000 Nov 24;87(11):972-83
references: 11090541
references: Am J Physiol Heart Circ Physiol. 2005 Feb;288(2):H971-6
references: 15358610
references: Am J Physiol Heart Circ Physiol. 2002 Nov;283(5):H1943-57
references: 12384473
references: Trends Cardiovasc Med. 1992 Sep-Dec;2(5):170-6
references: 21239250
references: Basic Res Cardiol. 2006 Jul;101(4):354-6
references: 16568250
references: Cardiovasc Res. 2003 Jun 1;58(3):582-8
references: 12798431
references: Circ Res. 2003 Apr 18;92(7):741-8
references: 12702642
references: Circ Res. 2002 Mar 22;90(5):602-8
references: 11909825
references: J Mol Cell Cardiol. 2003 May;35(5):525-37
references: 12738234
references: J Am Coll Cardiol. 2005 May 17;45(10):1707-15
references: 15893191
references: Circ Res. 2002 Aug 9;91(3):240-6
references: 12169650
references: Ann Thorac Surg. 2004 Sep;78(3):961-9; discussion 969
references: 15337028
references: Am J Physiol. 1997 Dec;273(6 Pt 2):H2931-6
references: 9435634
references: Am J Physiol Heart Circ Physiol. 2004 Apr;286(4):H1273-80
references: 14684373