Chen Jack P, Hou Dongming, Pendyala Lakshmana, Goudevenos John A, Kounis Nicholas G
Saint Joseph's Translational Research Institute, Saint Joseph's Heart and Vascular Institute, Atlanta, GA 30342, USA.
JACC Cardiovasc Interv. 2009 Jul;2(7):583-93. doi: 10.1016/j.jcin.2009.04.017.
The advent of drug-eluting stents (DES) has revolutionized the field of interventional cardiology. Their dramatic and persistent restenotic and target lesion revascularization advantages are unquestioned. However, concerns over the rare but potentially catastrophic risk of stent thrombosis (ST) have tempered universal acceptance of these devices. Although the precise mechanism of DES ST is undoubtedly multifactorial and as yet not fully elucidated, delayed or incomplete endothelial healing clearly plays a pivotal role. Detailed histopathological data have implicated a contributory allergic or hypersensitivity component, as verified by the Food and Drug Administration's Manufacturer and User Device Experience Center and the Research on Adverse Drug/device events And Reports (RADAR) project. These findings thus suggest a potential connection with the Kounis syndrome, the concurrence of acute coronary events with allergic, hypersensitivity, anaphylactic, or anaphylactoid reactions. Potential culprits responsible for this phenomenon include: arachidonic acid metabolites such as leukotrienes and thromboxane, proteolytic enzymes such as chymase and tryptase, histamine, cytokines, and chemokines. Additionally, inflammatory cells such as macrophages, T-lymphocytes, and mast cells are probably also contributory. Autopsy-confirmed infiltrates of various inflammatory cells including lymphocytes, plasma cells, macrophages, and eosinophils have been reported in all 3 vascular wall layers and are reminiscent of those associated with the Kounis syndrome. Although the concurrence of acute coronary syndromes with hypersensitivity reactions has been long established, the specific association with DES ST remains unproven. Potential incorporation of hypersensitivity suppressive agents might represent a promising paradigm shift from efficacy to safety in future DES designs.
药物洗脱支架（DES）的出现彻底改变了介入心脏病学领域。其显著且持久的减少再狭窄和靶病变血管重建的优势是毋庸置疑的。然而，对支架血栓形成（ST）这一罕见但可能具有灾难性风险的担忧，使得这些装置未能得到普遍接受。尽管DES导致ST的确切机制无疑是多因素的，且尚未完全阐明，但延迟或不完全的内皮愈合显然起着关键作用。详细的组织病理学数据表明存在过敏或超敏反应成分，美国食品药品监督管理局的制造商和用户设备体验中心以及药物/设备不良事件研究与报告（RADAR）项目已证实了这一点。因此，这些发现提示了与库尼斯综合征（Kounis syndrome）的潜在联系，即急性冠脉事件与过敏、超敏、过敏反应或类过敏反应同时发生。造成这种现象的潜在因素包括：花生四烯酸代谢产物，如白三烯和血栓素；蛋白水解酶，如糜酶和组织蛋白酶；组胺、细胞因子和趋化因子。此外，炎症细胞，如巨噬细胞、T淋巴细胞和肥大细胞可能也起了作用。尸检证实，在所有三层血管壁中均有各种炎症细胞浸润，包括淋巴细胞、浆细胞、巨噬细胞和嗜酸性粒细胞，这让人联想到与库尼斯综合征相关的炎症细胞浸润。尽管急性冠脉综合征与超敏反应同时发生早已得到证实，但与DES导致的ST之间的具体关联仍未得到证实。在未来DES的设计中，潜在地加入超敏反应抑制剂可能代表着从关注疗效到关注安全性的一个有前景的范式转变。
