Rapid and sustained coronary artery recanalization with combined bolus injection of recombinant tissue-type plasminogen activator and monoclonal antiplatelet GPIIb/IIIa antibody in a canine preparation.

Rapid and sustained coronary artery recanalization with combined bolus injection of recombinant tissue-type plasminogen activator and monoclonal antiplatelet GPIIb/IIIa antibody in a canine preparation.
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在犬制剂中联合推注重组组织型纤溶酶原激活剂和单克隆抗血小板 GPIIb/IIIa 抗体,可快速、持续地实现冠状动脉再通。

DOI:
10.1161/01.cir.77.3.670
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发表时间:
1988
期刊:
影响因子:
37.8
通讯作者:
Collen,D
Collen,D
中科院分区:
医学1区
文献类型:
--
作者:
Gold,HK;Coller,BS;Yasuda,T;Saito,T;Fallon,JT;Guerrero,JL;Leinbach,RC;Ziskind,AA;Collen,D

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在冠状动脉血栓形成和高度狭窄的犬标本中,研究了快速注射重组单链组织型纤溶酶原激活剂(rt-PA)和抗人血小板GPIIb/IIIa受体的鼠单克隆抗体(7 E3)的F(ab ')2片段[7 E3-F(ab')2]对冠状动脉血栓溶解和再闭塞的影响。以0.45 mg/kg的剂量静脉推注rt-PA,以15 min的间隔重复,直至发生再灌注(最多注射4次),在100 min内(33 ± 15 min,平均值± SD),7只犬中有5只发生再灌注。再灌注后迅速(一般在10分钟内),再闭塞,然后周期性复流和再闭塞。单次静脉注射0.8mg/kg的7 E3-F(ab ')2在100分钟内在6只狗中的两只中引起再灌注(19和37分钟),而没有随后的再闭塞。然后将不同量(0.1至0.8 mg/kg)的7 E3-F(ab ')2的单次推注与0.45 mg/kg的rt-PA的推注组合。0.8或0.6 mg/kg 7 E3-F(ab ')2和单次注射0.45 mg/kg rt-PA分别在6 +/- 3 min(n = 6,p小于0.01)和8 +/- 5 min(n = 5,p小于0.02)内实现稳定再灌注而无再闭塞。这些动物均未发生冠状动脉再闭塞。较低剂量(0.1至0.2 mg/kg)的7 E3-F(ab ')2没有显著缩短再灌注时间,也没有防止再闭塞。(250字处删节)
The effects of bolus injections of recombinant single-chain tissue-type plasminogen activator (rt-PA) and of F(ab')2 fragments of a murine monoclonal antibody (7E3) against the human platelet GPIIb/IIIa receptor [7E3-F(ab')2] on coronary arterial thrombolysis and reocclusion was studied in a canine preparation of coronary artery thrombosis superimposed on high-grade stenosis. Bolus intravenous injections of rt-PA at a dose of 0.45 mg/kg, repeated at 15 min intervals until reperfusion occurred (maximum of four injections) caused reperfusion in five of seven dogs within 100 min (33 +/- 15 min, mean +/- SD). Reperfusion was rapidly followed (generally within 10 min) by reocclusion and then by periods of cyclical reflow and reocclusion. A single intravenous injection of 7E3-F(ab')2 alone at 0.8 mg/kg caused reperfusion within 100 min in two of six dogs (19 and 37 min) without subsequent reocclusion. Single bolus injections of different amounts (0.1 to 0.8 mg/kg) of 7E3-F(ab')2 were then combined with bolus injections of 0.45 mg/kg of rt-PA. Stable reperfusion without reocclusion was accomplished with 0.8 or 0.6 mg/kg 7E3-F(ab')2 and a single injection of 0.45 mg/kg rt-PA within 6 +/- 3 min (n = 6, p less than .01) and 8 +/- 5 min (n = 5, p less than .02), respectively. None of these animals suffered reocclusion of the coronary artery. Lower doses (0.1 to 0.2 mg/kg) of 7E3-F(ab')2 did not significantly shorten the time to reperfusion and did not prevent reocclusion.(ABSTRACT TRUNCATED AT 250 WORDS)