Monoclonal antibody against the platelet glycoprotein (GP) IIb/IIIa receptor prevents coronary artery reocclusion after reperfusion with recombinant tissue-type plasminogen activator in dogs.
Monoclonal antibody against the platelet glycoprotein (GP) IIb/IIIa receptor prevents coronary artery reocclusion after reperfusion with recombinant tissue-type plasminogen activator in dogs.
复制标题
抗血小板糖蛋白 (GP) IIb/IIIa 受体的单克隆抗体可预防犬用重组组织型纤溶酶原激活剂再灌注后冠状动脉再闭塞。
DOI：
10.1172/jci113446
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Coller,BS
中科院分区：
文献类型：
--
作者：
Yasuda,T;Gold,HK;Fallon,JT;Leinbach,RC;Guerrero,JL;Scudder,LE;Kanke,M;Shealy,D;Ross,MJ;Collen,D;Coller,BS
在开胸犬的左前降支（LAD）冠状动脉中，通过收缩一段使狭窄大于90%（使血流量减少至基线的40±/- 10%）产生局部血栓，通过诱导内皮细胞损伤并灌注血液和凝血酶的混合物在狭窄的近端段放置血栓。重组组织型纤溶酶原激活剂（rt-PA）以15-30微克/公斤/分钟的速度静脉输注30或60分钟，8只狗在23 +/- 7分钟内（平均+/- SD）诱导冠状动脉再灌注，但尽管有肝素抗凝，除1只狗外，其余狗在7 +/- 5分钟内发生再闭塞。静脉注射针对血小板GPIIb/IIIa受体的单克隆抗体（7E3）的F（ab’）2片段0.8 mg/kg，在2小时的观察期内，10/10只狗可防止再闭塞（与单独rt-PA相比P < 0.001）。抗体消除adp诱导的血小板聚集，明显延长出血时间。分别只有2/7和1/6的狗静脉注射阿司匹林或双嘧达莫能预防1小时或更长时间的再闭塞。我们得出结论，单克隆抗体在用rt-PA成功溶栓闭塞的冠状动脉后非常有效地防止再闭塞。图片
Localized thrombosis was produced in the left anterior descending (LAD) coronary artery of open chest dogs by constricting a segment so as to produce greater than 90% stenosis (reducing blood flow to 40 +/- 10% of baseline), and placing a thrombus in the segment immediately proximal to the stenosis by inducing endothelial cell injury and instilling a mixture of blood and thrombin. Intravenous infusion of recombinant tissue-type plasminogen activator (rt-PA) at a rate of 15-30 micrograms/kg per min for 30 or 60 min in eight dogs induced coronary artery reperfusion within 23 +/- 7 min (mean +/- SD), but reocclusion occurred despite heparin anticoagulation in all but one of these dogs within 7 +/- 5 min. Intravenous injection of 0.8 mg/kg of the F(ab')2 fragment of a monoclonal antibody (7E3) directed against the platelet GPIIb/IIIa receptor, prevented reocclusion in 10/10 dogs during an observation period of 2 h (P less than 0.001 vs. rt-PA alone). The antibody abolished ADP-induced platelet aggregation and markedly prolonged the bleeding time. Intravenous aspirin or dipyridamole prevented reocclusion for 1 h or more in only 2/7 and 1/6 dogs, respectively. We conclude that the monoclonal antibody is very effective in preventing reocclusion after successful thrombolysis of occluded coronary arteries with rt-PA.Images