氯吡格雷、阿司匹林及联合治疗在猪高剪切力诱导支架内血栓形成离体模型中的作用

Effects of clopidogrel, aspirin and combined therapy in a porcine ex vivo model of high-shear induced stent thrombosis.

作者信息

Makkar R R, Eigler N L, Kaul S, Frimerman A, Nakamura M, Shah P K, Forrester J S, Herbert J M, Litvack F

机构信息

Department of Medicine, Burns and Allens Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

出版信息

Eur Heart J. 1998 Oct;19(10):1538-46. doi: 10.1053/euhj.1998.1042.

DOI:10.1053/euhj.1998.1042

PMID:9820993

Abstract

AIMS

Use of ticlopidine in coronary stenting is limited by delayed onset of action. We studied the effects of clopidogrel, a rapidly acting analog of ticlopidine alone, and in combination with aspirin, in inhibiting stent thrombosis.

METHODS

Unpolished nitinol stents were deployed in a porcine ex vivo arteriovenous shunt and exposed to flowing arterial blood at a shear rate of approximately 1500. s-1. Stent thrombus, platelet aggregation and bleeding times were measured at baseline and after treatment.

RESULTS

Intravenous clopidogrel produced a rapid (within 30 min) and dose-dependent inhibition of stent thrombosis, with 87% reduction at a dose of 10 mg.kg-1 (P < 0.001). Aspirin alone (10 mg.kg-1) was minimally effective (20% inhibition P > 0.05) in inhibiting stent thrombosis. Combined treatment with clopidogrel and aspirin produced 95-98% inhibition of stent thrombosis, even at low doses of clopidogrel (2.5-5.0 mg.kg-1) (P < 0.0001). At effective doses both clopidogrel and combined therapy produced significant prolongation of bleeding time (P < 0.05) and inhibition of platelet aggregation (P < 0.05).

CONCLUSION

Clopidogrel, either alone or combined with aspirin, may have a potential role in preventing stent thrombosis in high-risk clinical situations.

摘要

目的

噻氯匹定在冠状动脉支架置入术中的应用因起效延迟而受限。我们研究了氯吡格雷（一种起效迅速的噻氯匹定类似物）单独使用以及与阿司匹林联合使用对抑制支架内血栓形成的作用。

方法

将未抛光的镍钛合金支架植入猪的离体动静脉分流处，并使其暴露于剪切速率约为1500 s⁻¹的流动动脉血中。在基线和治疗后测量支架内血栓、血小板聚集和出血时间。

结果

静脉注射氯吡格雷可迅速（30分钟内）且剂量依赖性地抑制支架内血栓形成，剂量为10 mg·kg⁻¹时抑制率降低87%（P < 0.001）。单独使用阿司匹林（10 mg·kg⁻¹）在抑制支架内血栓形成方面效果甚微（抑制率20%，P > 0.05）。氯吡格雷与阿司匹林联合治疗即使在氯吡格雷低剂量（2.5 - 5.0 mg·kg⁻¹）时也能产生95 - 98%的支架内血栓形成抑制率（P < 0.0001）。在有效剂量下，氯吡格雷及联合治疗均显著延长出血时间（P < 0.05）并抑制血小板聚集（P < 0.05）。