抗血小板药物对猪急性心肌梗死再灌注后无再流的影响

Effects of anti-platelet drugs on myocardial no-reflow after acute myocardial infarction and reperfusion: experiment with mini-swine model

目的评价抗血小板药物防治猪急性心肌梗死(AMI)再灌注后无再流的作用。方法中华小型猪32只随机分成(1)对照组,(2)氯吡格雷与阿司匹林合用组(氯吡格雷第一天300mg/d,以后3mg·kg-1·d-1,阿司匹林10mg·kg-1·d-1,每天喂药一次,共3天),(3)替罗非斑治疗组(以15μg/kg静脉推注后继以0.5μg·kg-1·min-1的剂量持续静点直至实验结束)和(4)假手术组,每组8只。对照组和两治疗组行冠状动脉结扎3h,松解1h制备AMI再灌注模型。AMI前、后和再灌注后均行血流动力学测定和心肌声学造影(MCE)检查,最终行病理学分析。结果替罗非斑和氯吡格雷与阿司匹林合用组均使血小板最大聚集率显著降低(给药前分别为46.8%和45.7%,给药后分别为12.9%和14.3%)。与对照组相比,替罗非斑可显著改善心功能(P<0.05～0.01),冠脉血流量增加(对照组45.8%;替罗非斑组73.2%,P<0.01),减少无再流结扎区心肌范围(LA)(MCE对照组LA78.5%;病理染色测定LA为82.3%;替罗非斑组:MCE染色测定LA22.8%病理染色测定LA为23.2%(P<0.01),减少无再流结扎区心肌坏死范围(NA)(对照组:98.5%;替罗非斑组:89.2%LA,P<0.05)。然而,氯吡格雷与阿司匹林合用组血流动力学指标、冠脉血流量、无再流范围及心肌坏死范围与对照组相比差异无统计学意义(P均>0.05)。结论替罗非斑能有效地防治心肌梗死再灌注后无再流,而氯吡格雷与阿司匹林合用则完全无效。

Objective To evaluate the effects of anti-platelet drugs on myocardial no-reflow after acute myocardial infarction （AMI） and reperfusion. Methods Thirty-two mini-swine were randomized into 4 equal groups ： Control Group, without any intervention; Group A ～ C, pretreated with aspirin-clopidogrel（A-C） combination （300 mg loading dose followed by 75 mg per day of clopidogrel and 10 mg · kg^-1 · d^-1 of aspirin for 3 days）, Group Tirofiban, given an intravenous infusion of tirofiban （ 15 μg/kg in intravenous bolus followed by 0. 5 μg· kg^-1 ·min^- 1 in continuous intravenous infusion from 30 rain before occlusion to the end of protocol ; and Sham Operation Group, undergoing sham operation. The former 3 groups underwent three-hour occlusion of the left anterior descending （LAD） coronary artery followed by one-hour reperfusion Before the adminisfration of drngs and hefore lipation of LAD flood sanpks were collocfed to detoif the platelet aggregation rate （PAR）. Hemodynamic examination and myocardial contrast echocardiography （MCE） were performed before AMI, 3 h after AMI, and 1 h after reperfusion. The coronary ligation area （LA） and area of no-reflow （ANR） were determined with both MCE in vivo and pathological examination after the swine were killed. Results The platelet aggregation rates （MAR） after AMI were 46. 8% and 45.7% respectively in tirofiban group and A-C Combination group, and significantly decreased to 12. 9% and 14. 3% respectively after the administration of drugs （ both P 〈 0. 01 ） with equivalent potency （ P 〉 0. 05 ）.The left ventricular function was significantly improved in tirofiban group in comparison with control group （P 〈0. 05～0. 01 ）, the coronary blood flow volume （CBV） 1 h after reperfusion was 73.2% in tirofiban group, significantly higher than that of control group （45.8%, P 〈0. 01 ）, and the ANR of tirofiban group was 22. 8% and 23.2% judged by MCE and pathological examination respectively, both significantly smaller than those of control group （ 78.5% and 82. 3% , both P 〈 0. 01 ） , and the NA of tirofiban group was 89. 2% , significantly smaller than that of Control Group （ 98.5% , P 〈 0.05 ）. However, there were not significant differences in left ventricular function, central blood volume, ANR and NA between A-C combination group and control group （ all P 〉 0. 05 ）. Conclusion Tirofiban is markedly effective in attenuating myocardial no-reflow after reperfusion; in contrast, A-C combination is totally ineffective.