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一氧化氮供体可抑制急性心肌梗死和不稳定型心绞痛中的血小板活化。

Platelet activation in acute myocardial infarction and unstable angina is inhibited by nitric oxide donors.

作者信息

Langford E J, Wainwright R J, Martin J F

机构信息

Cardiology Department, King's College Hospital, London, UK.

出版信息

Arterioscler Thromb Vasc Biol. 1996 Jan;16(1):51-5. doi: 10.1161/01.atv.16.1.51.

DOI:10.1161/01.atv.16.1.51
PMID:8548426
Abstract

Platelet activation and thrombus formation within the coronary artery are major factors in acute myocardial infarction (AMI) and unstable angina (UA), and continuing platelet activation is associated with an adverse prognosis. We assessed platelet activation by using flow cytometry to measure platelet surface expression of P-selectin and glycoprotein IIb/IIIa in 20 patients with AMI and 20 with UA, all of whom were treated with aspirin. Platelet studies were repeated after the infusion of a nitric oxide donor (glyceryl trinitrate or S-nitrosoglutathione) that produced a fall in mean arterial pressure of no more than 10 mm Hg. P-selectin was expressed on 2.5% (range, 1.4% to 6.3%) of platelets from AMI and 2.3% (range, 1.6% to 3.3%) from UA subjects compared with 1.0% (range, 0.6% to 1.9%) of platelets from 20 control volunteers without angina (P < .001). Glycoprotein IIb/IIIa expression was 101.6 +/- 2.7 arbitrary units of relative fluorescence in AMI and 100.2 +/- 3.3 in UA compared with 87.8 +/- 2.5 in control subjects (P < .01). In both AMI and UA, S-nitrosoglutathione reduced P-selectin (P < .001) and glycoprotein IIb/IIIa (P < .05) expression, as did glyceryl trinitrate (P < .02 and P < .01, respectively). In 3 of 20 patients receiving glyceryl trinitrate the lowest dose was not tolerated due to headache or hypotension. These findings show that platelet activation persists in AMI and UA despite aspirin treatment and that this can be inhibited by using glyceryl trinitrate or S-nitrosoglutathione. S-nitrosoglutathione is better tolerated at the doses required.

摘要

冠状动脉内的血小板活化和血栓形成是急性心肌梗死(AMI)和不稳定型心绞痛(UA)的主要因素,持续的血小板活化与不良预后相关。我们通过流式细胞术检测20例AMI患者和20例UA患者血小板表面P-选择素和糖蛋白IIb/IIIa的表达来评估血小板活化情况,所有患者均接受阿司匹林治疗。在输注一氧化氮供体(硝酸甘油或S-亚硝基谷胱甘肽)使平均动脉压下降不超过10 mmHg后重复进行血小板研究。与20名无心绞痛的对照志愿者的血小板相比,AMI患者血小板上P-选择素的表达率为2.5%(范围1.4%至6.3%),UA患者为2.3%(范围1.6%至3.3%),而对照志愿者为1.0%(范围0.6%至1.9%)(P <.001)。AMI患者糖蛋白IIb/IIIa的表达为101.6±2.7相对荧光任意单位,UA患者为100.2±3.3,而对照受试者为87.8±2.5(P <.01)。在AMI和UA患者中,S-亚硝基谷胱甘肽均可降低P-选择素(P <.001)和糖蛋白IIb/IIIa(P <.05)的表达,硝酸甘油也有同样作用(分别为P <.02和P <.01)。20例接受硝酸甘油治疗的患者中有3例因头痛或低血压无法耐受最低剂量。这些结果表明,尽管接受了阿司匹林治疗,AMI和UA患者的血小板活化仍然持续存在,而使用硝酸甘油或S-亚硝基谷胱甘肽可以抑制这种活化。在所需剂量下,S-亚硝基谷胱甘肽的耐受性更好。

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