Document Detail

Thrombin and its receptor enhance ST-segment elevation in acute myocardial infarction by activating the KATP channel.
MedLine Citation:
PMID:  20386871     Owner:  NLM     Status:  MEDLINE    
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.
Ming Long; Lei Yang; Genya Huang; Liping Liu; Yugang Dong; Zhimin Du; Anli Tang; Chenghen Hu; Ruimin Gu; Xiuren Gao; Lilong Tang
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-04-09
Journal Detail:
Title:  Molecular medicine (Cambridge, Mass.)     Volume:  16     ISSN:  1528-3658     ISO Abbreviation:  Mol. Med.     Publication Date:    2010 Jul-Aug
Date Detail:
Created Date:  2010-07-19     Completed Date:  2010-11-08     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  9501023     Medline TA:  Mol Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  322-32     Citation Subset:  IM    
Division of Cardiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
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MeSH Terms
Analysis of Variance
Electrocardiography / drug effects*,  methods
Guinea Pigs
Hirudins / pharmacology
KATP Channels / metabolism*
Myocardial Infarction / metabolism*
Receptors, Thrombin / metabolism*
Thrombin / antagonists & inhibitors,  metabolism*
Reg. No./Substance:
0/Hirudins; 0/KATP Channels; 0/Receptors, Thrombin; EC

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