Nitroaspirin plus clopidogrel versus aspirin plus clopidogrel against platelet thromboembolism and intimal thickening in mice
Nitroaspirin plus clopidogrel versus aspirin plus clopidogrel against platelet thromboembolism and intimal thickening in mice
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DOI：
10.1160/th04-07-0464
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发表时间：
2005-03-01
影响因子：
6.7
通讯作者：
Gresele, P
中科院分区：
文献类型：
--
作者：
Momi, S;Pitchford, SC;Gresele, P
氯吡格雷加阿司匹林是接受经皮冠状动脉介入术和支架植入术患者的首选治疗方法，但不能预防再狭窄。NCX-4016是一种释放一氧化氮的阿司匹林（硝基阿司匹林），与阿司匹林相比，具有更广泛的抗血小板作用，具有上级抗血栓活性，并可减少动物动脉损伤后的再狭窄。本研究的目的是比较硝基阿司匹林+氯吡格雷与阿司匹林+氯吡格雷在小鼠血小板肺血栓栓塞、出血和内膜增厚模型中的组合。药物口服给药5天，抗血栓形成的影响进行了评价，对胶原蛋白加肾上腺素诱导的肺血栓栓塞症，出血的影响，尾部横断出血时间和新生内膜增生的影响，光化学损伤的股动脉的组织形态学。硝基阿司匹林加氯吡格雷组（-56%，p < 0.05 vs对照组）比阿司匹林加氯吡格雷组（-26%，p <0.05 vs对照组）显著且更有效地减少了肺血小板栓塞。体外血小板聚集抑制最大的硝基阿司匹林加氯吡格雷。阿司匹林加氯吡格雷明显延长出血时间，而硝基阿司匹林加氯吡格雷引起的延长较小。硝基阿司匹林加氯吡格雷显着减少股动脉内膜增厚，而阿司匹林加氯吡格雷无效。硝基阿司匹林+氯吡格雷在小鼠中比阿司匹林+氯吡格雷更有效，出血更少;如果这些数据在其他动物模型中得到证实，硝基阿司匹林+氯吡格雷可能代表一种新的方案，用于接受冠状动脉血运重建术的患者。
Clopidogrel plus aspirin is the treatment of choice for patients undergoing percutaneous, coronary interventions with stenting, but it does not prevent restenosis. NCX-4016,a nitric oxide-releasing aspirin (nitroaspirin), exerts a wider range of antiplatelet actions compared to aspirin, superior antithrombotic activity and reduces restenosis after arterial injury in animals. The aim of the present study was to compare the combination of nitroaspirin plus clopidogrel with aspirin plus clopidogrel in a model of platelet pulmonary thromboembolism, bleeding and intimal thickening in mice. Drugs were administered orally for 5 days; the antithrombotic effects were evaluated against collagen plus epinephrine-induced pulmonary thromboembolism, the haemorrhagic effects by tail transection bleeding time and the effects on neointima proliferation by histomorphology of photochemically injured femoral arteries. Lung platelet emboli were reduced significantly and more effectively by nitroaspirin plus clopidogrel (-56%, p < 0.05 vs control) than by aspirin plus clopidogrel (-26%, p < 0.05 vs control). Ex vivo platelet aggregation was inhibited maximally by nitroaspirin plus clopidogrel. Aspirin plus clopidogrel strikingly prolonged the bleeding time while nitroaspirin plus clopidogrel induced a lesser prolongation. Nitroaspirin plus clopidogrel significantly reduced intimal thickening of the femoral artery while aspirin plus clopidogrel was ineffective. Nitroaspirin plus clopidogrel is more effective and less prohaemorrhagic than aspirin plus clopidogrel in mice; provided these data are confirmed in other animal models, nitroaspirin plus clopidogrel may represent a new regimen to be tested in patients undergoing coronary revascularization procedures.