Zhao Jing-lin, Yang Yue-jin, Wu Yong-jian, Jing Zhi-cheng, You Shi-jie, Yang Wei-xian, Meng Liang, Tian Yi, Chen Ji-lin, Gao Run-lin, Chen Zai-jia
Department of Cardiology, Fuwai Heart Hospital, Beijing 100037, China.
Zhonghua Yi Xue Za Zhi. 2005 Aug 17;85(31):2187-91.
To evaluate the effects of anti-platelet drugs on myocardial no-reflow after acute myocardial infarction (AMI) and reperfusion.
Thirty-two mini-swine were randomized into 4 equal groups: Control Group, without any intervention; Group A approximately C, pretreated with aspirin-clopidogrel (A-C) combination (300 mg loading dose followed by 75 mg per day of clopidogrel and 10 mg x kg(-1) x d(-1) of aspirin for 3 days), Group Tirofiban, given an intravenous infusion of tirofiban (15 microg/kg in intravenous bolus followed by 0.5 microg x kg(-1) x min(-1) in continuous intravenous infusion from 30 min 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.
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).
Tirofiban is markedly effective in attenuating myocardial no-reflow after reperfusion; in contrast, A-C combination is totally ineffective.
评估抗血小板药物对急性心肌梗死(AMI)及再灌注后心肌无复流的影响。
32只小型猪随机分为4组,每组8只:对照组,不做任何干预;A - C联合组,给予阿司匹林 - 氯吡格雷联合预处理(氯吡格雷负荷剂量300 mg,随后每天75 mg,阿司匹林10 mg·kg⁻¹·d⁻¹,共3天);替罗非班组,静脉输注替罗非班(静脉推注15 μg/kg,随后从冠状动脉闭塞前30分钟至实验结束持续静脉输注0.5 μg·kg⁻¹·min⁻¹);假手术组,行假手术。前3组均进行3小时左前降支(LAD)冠状动脉闭塞,随后1小时再灌注。在给药前及LAD闭塞前采集血液样本检测血小板聚集率(PAR)。在AMI前、AMI后3小时及再灌注后1小时进行血流动力学检查及心肌对比超声心动图(MCE)检查。猪处死后,通过体内MCE及病理检查确定冠状动脉结扎区域(LA)和无复流区域(ANR)。
AMI后替罗非班组和A - C联合组的血小板聚集率(MAR)分别为46.8%和45.7%,给药后分别显著降至12.9%和14.3%(均P < 0.01),且效力相当(P > 0.05)。与对照组相比,替罗非班组左心室功能显著改善(P < 0.05 - 0.01),再灌注后1小时替罗非班组冠状动脉血流量(CBV)为73.2%,显著高于对照组(45.8%,P < 0.01),替罗非班组通过MCE和病理检查判断的ANR分别为22.8%和23.2%,均显著小于对照组(78.5%和82.3%,均P < 0.01),替罗非班组的坏死面积(NA)为89.2%,显著小于对照组(98.5%,P < 0.05)。然而,A - C联合组与对照组在左心室功能、中心血量、ANR和NA方面均无显著差异(均P > 0.05)。
替罗非班在减轻再灌注后心肌无复流方面显著有效;相比之下,A - C联合治疗完全无效。