title: Thrombin and its receptor enhance ST-segment elevation in acute myocardial infarction by activating the KATP channel.
abstract: ST-segment elevation is the major clinical criterion for committing patients with chest pain to have emergent coronary revascularizations; however, the mechanism responsible for ST-segment elevation is unknown. In a guinea pig model of ST-segment elevation acute myocardial infarction (AMI), local application of hirudin, a thrombin antagonist, significantly decreased AMI-induced ST-segment elevation in a dose-dependent manner. Hirudin-induced (5 antithrombin units [ATU]) decrease in ST elevation was reversed by 250 nmol/L thrombin receptor activator peptide (TRAP). TRAP (250 nmol/L [100 microL]) significantly induced ST-segment elevation in hearts without AMI. The TRAP effect was blocked by 4 mg/kg glibenclamide and 4 mg/kg HMR1098 and partially blocked by 3 mg/kg 5HD. Pinacidil (0.45 mg/kg) simulated the effect of TRAP (250 nmol/L [100 microL]) on hearts without AMI. Moreover, single-channel recordings showed that TRAP induced ATP-sensitive K+ channel (KATP channel) activity, and this effect was blocked by HMR1098 but not 5HD. Finally, TRAP significantly shortened the monophasic action potential (MAP) at 90% repolarization (MAP90) and epicardial MAP (EpiMAP) duration. These effects of TRAP were completely reversed by HMR1098 and partially reversed by 5HD. Thrombin and its receptor activation enhanced ST-segment elevation in an AMI model by activating the sarcolemmal KATP channel.
authors.affiliation: Division of Cardiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Long
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.forename: Genya
authors.initials: G
authors.lastname: Huang
authors.forename: Liping
authors.initials: L
authors.lastname: Liu
authors.forename: Yugang
authors.initials: Y
authors.lastname: Dong
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Du
authors.forename: Anli
authors.initials: A
authors.lastname: Tang
authors.forename: Chenghen
authors.initials: C
authors.lastname: Hu
authors.forename: Ruimin
authors.initials: R
authors.lastname: Gu
authors.forename: Xiuren
authors.initials: X
authors.lastname: Gao
authors.forename: Lilong
authors.initials: L
authors.lastname: Tang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D004562:Electrocardiography / Q000187:drug effects* / Q000379:methods; D006168:Guinea Pigs; D006629:Hirudins / Q000494:pharmacology; D054086:KATP Channels / Q000378:metabolism*; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism*; D010477:Perfusion; D018179:Receptors, Thrombin / Q000378:metabolism*; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D006629:Hirudins; D054086:KATP Channels; D018179:Receptors, Thrombin; D013917:Thrombin
references.citation: Circ Res. 1991 Jun;68(6):1693-702
references.pmid: 2036719
references.citation: J Am Coll Cardiol. 1989 Oct;14(4):1053-66
references.pmid: 2551947
references.citation: Br J Pharmacol. 2008 May;154(1):41-50
references.pmid: 18297097
references.citation: N Engl J Med. 2008 May 22;358(21):2218-30
references.pmid: 18499566
references.citation: Am J Physiol Heart Circ Physiol. 2008 Sep;295(3):H990-H998
references.pmid: 18621854
references.citation: Circulation. 1984 Mar;69(3):593-604
references.pmid: 6692520
references.citation: Circulation. 1986 Aug;74(2):401-9
references.pmid: 3731429
references.citation: J Mol Cell Cardiol. 1984 May;16(5):389-94
references.pmid: 6737481
references.citation: Circ Res. 2000 Nov 10;87(10):837-9
references.pmid: 11073877
references.citation: Am J Physiol. 1991 Nov;261(5 Pt 2):H1387-91
references.pmid: 1951725
references.citation: J Pharmacol Exp Ther. 1996 Dec;279(3):1365-78
references.pmid: 8968361
references.citation: Pharmacol Rev. 2001 Jun;53(2):245-82
references.pmid: 11356985
references.citation: Ann Surg. 1954 Nov;140(5):675-82
references.pmid: 13208115
references.citation: Cell. 1991 Mar 22;64(6):1057-68
references.pmid: 1672265
references.citation: Circ Res. 1990 Oct;67(4):835-43
references.pmid: 2119912
references.citation: Circ Res. 1996 Apr;78(4):553-63
references.pmid: 8635212
references.citation: Acta Physiol (Oxf). 2008 May;193(1):25-36
references.pmid: 18005217
references.citation: Am J Cardiol. 2006 Jan 1;97(1):48-54
references.pmid: 16377283
references.citation: Circ Res. 1980 Jun;46(6):814-25
references.pmid: 7379247
references.citation: Cardiovasc Drugs Ther. 1994 Oct;8(5):749-56
references.pmid: 7873472
references.citation: Eur J Pharmacol. 1998 May 1;348(1):11-23
references.pmid: 9650826
references.citation: Basic Res Cardiol. 1984 Jan-Feb;79(1):59-67
references.pmid: 6732720
references.citation: J Pharmacol Exp Ther. 1992 Feb;260(2):702-8
references.pmid: 1738118
references.citation: Exp Biol Med (Maywood). 2008 Jan;233(1):84-93
references.pmid: 18156310
references.citation: Circ Res. 1960 Jul;8:780-7
references.pmid: 14441272
references.citation: Br Heart J. 1983 Aug;50(2):127-34
references.pmid: 6882602
references.citation: Mol Med. 2008 Mar-Apr;14(3-4):131-40
references.pmid: 18224254
references.citation: Arterioscler Thromb. 1992 May;12(5):548-53
references.pmid: 1576116
references.citation: Circulation. 2005 Sep 20;112(12):1701-10
references.pmid: 16157773
references.citation: J Biol Chem. 1995 Sep 15;270(37):21619-25
references.pmid: 7665575
references.citation: Cardiovasc Res. 1986 Oct;20(10):740-51
references.pmid: 3791340
references.citation: Circulation. 1993 Oct;88(4 Pt 1):1845-51
references.pmid: 8403330
references.citation: Cardiovasc Res. 1997 Aug;35(2):256-72
references.pmid: 9349389
references.citation: Cardiovasc Res. 1999 Jan;41(1):25-40
references.pmid: 10325951