低剂量氯吡格雷在冠状动脉再狭窄家猪模型中应用的初步探讨

The initial use investigation of lower dose clopidogrel in the domestic porcine model for coronary artery restenosis

目的评价低剂量氯吡格雷在冠状动脉再狭窄家猪模型中的应用效果。方法选取健康家猪6头,抽取静脉血测定ADP(Adenosine Diphosphate,二磷酸腺苷)诱导的血小板聚集率作为基础值,然后开始喂食氯吡格雷(25mg/d)和常规剂量的阿司匹林,开始给药后第4天行介入手术构建冠状动脉过度扩张再狭窄模型并行支架植入术,同时在给药后第4、8﹑14天再次抽血测定ADP诱导的血小板聚集率,评价氯吡格雷对血小板聚集率的抑制效果,记录术后压迫止血情况及术中、术后的安全性,14天时处死动物并血管取材评价支架内血栓情况。采用SPSS10.0进行统计学分析。结果家猪平均体重为(23.1±4.4)Kg,ADP诱导的血小板聚集率基础值为(43.08±5.06)%。用药后第4天,血小板聚集率值较基础值明显下降[(29.05±9.26)%:(43.08±5.06)%,P=0.008],用药后8天血小板聚集率值进一步下降,用药后14天,血小板聚集率值趋于稳定,达到并维持抗血小板聚集的效果,术中和术后24小时均未发生冠状动脉事件,14天时血管取材病理切片未见支架内血栓形成。结论在冠状动脉再狭窄家猪模型中,低剂量氯吡格雷可以达到抑制ADP诱导的血小板聚集的效果,同时低剂量氯吡格雷联合常规剂量的阿司匹林可以保证冠状动脉再狭窄家猪模型的安全性,并降低实验费用。

Objective To investigate the effect and safety of the lower clopidogrel in domestic porcine model for coronary artery restenosis.Methods We took the 6 samples of domestic porcine blood and measured the inhibition of platelet aggregation value before administration of Clopidogrel and 4-day,8-day,14-day after administration.4-day after administration,we build the porcine model for coronary artery restenosis and implant stents.We evaluate the effects of inhibition of platelet aggregation induced by ADP,compression hemostasis and safety of peri-operation.The data were analyzed with SPSS 10.0.Result 4-day after administration the value of inhibition of platelet aggregation is lower than base line significantly,[(29.05±9.26)% vs.(43.08±5.06)%,P=0.008].8-day,14-day after administration,the inhibitions of Platelet Aggregation are still low.No peri-operation coronary events were found.After 14-day,no thrombosis was found in the pathological sections.Conclusions Our data demonstrates that administration of Clopidogrel 25 mg/d can inhibit platelet aggregation induced by ADP,administration of Clopidogrel 25 mg/d combining with routine aspirin may provide the peri-operation safety and reduce the cost in the domestic porcine model for coronary artery restenosis.