Thrombin and its receptor enhance ST-segment elevation in acute myocardial infarction by activating the KATP channel.
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.
Long
Ming
M
Division of Cardiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Yang
Lei
L
Huang
Genya
G
Liu
Liping
L
Dong
Yugang
Y
Du
Zhimin
Z
Tang
Anli
A
Hu
Chenghen
C
Gu
Ruimin
R
Gao
Xiuren
X
Tang
Lilong
L
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*
D006629:Hirudins; D054086:KATP Channels; D018179:Receptors, Thrombin; D013917:Thrombin
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