Effects of unfractionated heparin and glycoprotein IIb/IIIa antagonists versus bivalirdin on myeloperoxidase release from neutrophils
Effects of unfractionated heparin and glycoprotein IIb/IIIa antagonists versus bivalirdin on myeloperoxidase release from neutrophils
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DOI：
10.1161/atvbaha.107.144576
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发表时间：
2007-08-01
影响因子：
8.7
通讯作者：
Smyth, Susan S.
中科院分区：
文献类型：
--
作者：
Li, Guohong;Keenan, Alison C.;Smyth, Susan S.
目的-本研究的目的是确定经皮冠状动脉介入治疗（PCI）期间的连续治疗是否影响全身炎症或血小板活化的标志物。尽管作用机制不同，在REPLACE-2和ACUITY试验中，与普通肝素（UFH）加计划使用GPIIb/IIIa拮抗剂相比，PCI期间使用比伐卢定直接凝血酶抑制剂提供了类似的围手术期和慢性缺血并发症保护。依替巴肽PCI术后两组患者白细胞介素（IL）-6和C反应蛋白（CRP）均一过性升高。在UFH +依替巴肽组，而不是比伐卢定组，髓过氧化物酶（MPO）水平升高2.3倍以上的基线（P = 0.004）后立即PCI。在体外试验中，肝素和较小程度的依诺肝素，但不是比伐卢定或依替巴肽，刺激MPO从中性粒细胞释放并与中性粒细胞结合和中性粒细胞活化。一个小鼠模型的腔内股动脉剥脱被用来进一步调查的重要性，MPO在动脉injury.Conclusions的背景下，辅助治疗在PCI可能有不希望的影响中性粒细胞活化，MPO释放，全身炎症。
Objectives - The objective of this study was to determine whether adjunctive therapy during percutaneous coronary intervention ( PCI) affects markers of systemic inflammation or platelet activation. Despite different mechanisms of action, direct-thrombin inhibition with bivalirudin during PCI provided similar protection from periprocedural and chronic ischemic complications as compared with unfractionated heparin ( UFH) plus planned use of GPIIb/IIIa antagonists in the REPLACE-2 and ACUITY trials.Methods and Results - Patients undergoing nonurgent PCI of a native coronary artery were randomized to receive adjunctive therapy with bivalirudin or UFH + eptifibatide. Interleukin (IL)- 6 and C-reactive protein (CRP) transiently increased in both groups after PCI. In the UFH + eptifibatide, but not the bivalirudin group, myeloperoxidase (MPO) levels were elevated 2.3-fold above baseline (P = 0.004) immediately after PCI. In an in vitro assay, heparin and to a lesser extent enoxaparin, but not bivalirudin or eptifibatide, stimulated MPO release from and binding to neutrophils and neutrophil activation. A mouse model of endoluminal femoral artery denudation was used to investigate further the importance of MPO in the context of arterial injury.Conclusions - Adjuvant therapy during PCI may have undesired effects on neutrophil activation, MPO release, and systemic inflammation.