Thrombin and Its Receptor Enhance ST-Segment Elevation in Acute Myocardial Infarction by Activating the KATP Channel
Thrombin and Its Receptor Enhance ST-Segment Elevation in Acute Myocardial Infarction by Activating the KATP Channel
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DOI：
10.2119/molmed.2010.00006
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发表时间：
2010-07-01
影响因子：
5.7
通讯作者：
Tang, Lilong
中科院分区：
文献类型：
--
作者：
Long, Ming;Yang, Lei;Tang, Lilong
st段抬高是胸痛患者急诊冠脉重建术的主要临床判断标准；然而，导致st段抬高的机制尚不清楚。在st段抬高型急性心肌梗死（AMI）豚鼠模型中，局部应用水蛭素（一种凝血酶拮抗剂）可显著降低AMI诱导的st段抬高，且呈剂量依赖性。250 nmol/L凝血酶受体激活肽（TRAP）可逆转水蛭素诱导的（5个抗凝血酶单位（ATU）） ST段升高。250 nmol/L (100 [A。L))显著诱导无AMI心脏的st段抬高。4 mg/kg格列苯脲和4 mg/kg HMR1098阻断TRAP作用，3 mg/kg 5HD部分阻断TRAP作用。Pinacidil （0.45 mg/kg）模拟TRAP （250 nmol/L (100 [IL)）对无AMI心脏的影响。此外，单通道记录显示，TRAP诱导atp敏感的K+通道（K- atp通道）活性，HMR1098能阻断这种作用，而5HD不能。最后，TRAP显著缩短了90%复极时的单相动作电位（MAP）和心外膜MAP （EpiMAP）持续时间。TRAP的这些作用被HMR1098完全逆转，被5HD部分逆转。凝血酶及其受体激活通过激活肌层K-ATP通道增强AMI模型st段抬高。(C) 2010年，范斯坦医学研究所，www.feinsteininstitute.org
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 AMIinduced 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 [A. L)) significantly induced STsegment 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 [IL)) on hearts without AMI. Moreover, single-channel recordings showed that TRAP induced ATP-sensitive K+ channel (K-ATP 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 K-ATP channel. (C) 2010 The Feinstein Institute for Medical Research, www.feinsteininstitute.org