Comparison of intravenous bolus injection or continuous infusion of recombinant single chain urokinase-type plasminogen activator (saruplase) for thrombolysis. A canine model of combined coronary arterial and femoral venous thrombosis.

Comparison of intravenous bolus injection or continuous infusion of recombinant single chain urokinase-type plasminogen activator (saruplase) for thrombolysis. A canine model of combined coronary arterial and femoral venous thrombosis.
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静脉推注或持续输注重组单链尿激酶型纤溶酶原激活剂(沙鲁普酶)溶栓的比较。

DOI:
10.1182/blood.v76.8.1558.bloodjournal7681558
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发表时间:
1990
期刊:
影响因子:
20.3
通讯作者:
D. Collen
D. Collen
中科院分区:
医学1区
文献类型:
--
作者:
H. Rapold;Z. Wu;T. Stassen;F. J. Van de Werf;D. Collen

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研究了重组无糖基化全长单链尿激酶型纤溶酶原激活剂(rscu-PA, saruplase)单次静脉滴注或连续滴注60分钟的溶栓效果,并将5只铜线圈诱导的冠状动脉血栓和125i -纤维蛋白标记的股静脉凝块合并纳入随机盲法组。输注1 mg/kg recu-PA (I组)诱导5只狗中的4只冠状动脉再通,98 +/- 1%(平均+/- SEM)静脉凝块溶解。注射1 mg/kg recu-PA (II组),5只狗中有3只出现再流,88 +/- 5%的静脉凝块溶解。注射0.5 mg/kg的rescue - pa (III组),5只狗中有3只实现了血流,52只+/- 6%的静脉血栓溶解。静脉注射0.5 mg/kg rscu-PA (IV组),5只狗中有4只出现再流,48只出现+/- 12%的静脉血栓溶解。安慰剂输注(V组)与5只狗中1只的晚期再通和18 +/- 8%的静脉凝块溶解相关。ⅰ组和ⅱ组均未见冠状动脉再闭塞,而ⅲ组3只动物中有2只出现冠状动脉再闭塞,ⅳ组4只动物中有3只出现冠状动脉再闭塞(P = 0.02)。反应性动物滴注rscu-PA 0.5或1 mg/kg时回流时间为22 +/- 5分钟,单次注射0.5或1 mg/kg时回流时间为14 +/- 1分钟(P = .14)。注射1 mg/kg rscu-PA的5只狗和输注1 mg/kg rscu-PA的3只狗的纤维蛋白原和α 2-抗纤溶酶的消耗低于基线水平的25%,但接受0.5 mg/kg rscu-PA的狗没有出现纤维蛋白原和α 2-抗纤溶酶的消耗(P < 0.001)。注射后血浆清除率分别为170 +/- 44和230 +/- 30 mL/min,注射1 mg/kg和0.5 mg/kg剂量的rscu-PA时血浆清除率分别为190 +/- 47和310 +/- 56 mL/min。因此,对于冠状动脉溶栓和静脉溶栓,静脉大剂量注射rscu-PA (saruplase)似乎与静脉输注60分钟具有同等效力。这种动脉和静脉联合溶栓的动物模型可能有助于评估新的溶栓策略。
The thrombolytic efficacy of recombinant unglycosylated full length single chain urokinase-type plasminogen activator (rscu-PA, saruplase), applied either as single intravenous bolus or as a continuous infusion over 60 minutes, was studied in 5 randomized blinded groups of 5 dogs with combined copper coil induced coronary artery thrombosis and 125I-fibrin labeled femoral vein clots. Infusion of 1 mg/kg recu-PA (group I) induced coronary recanalization in 4 of 5 dogs and 98 +/- 1% (mean +/- SEM) venous clot lysis. Bolus injection of 1 mg/kg recu-PA (group II) caused reflow in 3 of 5 dogs and 88 +/- 5 percent venous clot lysis. Infusion of 0.5 mg/kg rescu-PA (group III) achieved reflow in 3 of 5 dogs and 52 +/- 6% venous clot lysis. Bolus injection of 0.5 mg/kg rscu-PA (group IV) induced reflow in 4 of 5 dogs and 48 +/- 12% venous clot lysis. Placebo infusion (group V) was associated with late recanalization in 1 of 5 dogs and 18 +/- 8% venous clot lysis. Coronary artery reocclusion after reflow was not observed in groups I and II, but occurred in 2 of 3 animals in group III and in 3 of 4 animals in group IV (P = .02). The time to reflow in responsive animals was 22 +/- 5 minutes with infusion of 0.5 or 1 mg/kg rscu-PA and 14 +/- 1 minute with bolus injection of 0.5 or 1 mg/kg (P = .14). Depletion of fibrinogen and alpha 2-antiplasmin to less than 25% of baseline levels was observed in the 5 dogs given 1 mg/kg rscu-PA by bolus and in 3 of the 5 dogs given 1 mg/kg rscu-PA via infusion, but in none of the dogs that received 0.5 mg/kg rscu-PA (P less than .001). Plasma clearance rates were 170 +/- 44 and 230 +/- 30 mL/minute after bolus injection and 190 +/- 47 and 310 +/- 56 mL/minute during infusion of rscu-PA for the 1 mg/kg and 0.5 mg/kg doses respectively. Thus, intravenous bolus injection of rscu-PA (saruplase) appears to be equipotent to an infusion over 60 minutes for both coronary and venous thrombolysis. This animal model of combined arterial and venous thrombolysis may be useful for the evaluation of new thrombolytic strategies.
DOI: 10.1016/0735-1097(90)90327-l
发表时间: 1990-12
影响因子: 24
作者:
Tsunehiro Yasuda;H. Gold;R. Leinbach;Tomiyoshi Saito;J.Luis Guerrero;Ik-Kyung Jang;Robert D. Holt;John T. Fallon;D. Collen
通讯作者: Tsunehiro Yasuda;H. Gold;R. Leinbach;Tomiyoshi Saito;J.Luis Guerrero;Ik-Kyung Jang;Robert D. Holt;John T. Fallon;D. Collen
DOI: 10.1161/01.cir.79.4.920
发表时间: 1989-04-01
期刊: CIRCULATION
影响因子: 37.8
作者:
JANG, IK;GOLD, HK;COLLEN, D
通讯作者: COLLEN, D
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DOI: 10.1161/01.cir.77.3.670
发表时间: 1988
期刊: Circulation
影响因子: 37.8
作者:
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通讯作者: Collen,D
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
发表时间: 1988
期刊: The Journal of clinical investigation
影响因子: --
作者:
Yasuda,T;Gold,HK;Fallon,JT;Leinbach,RC;Guerrero,JL;Scudder,LE;Kanke,M;Shealy,D;Ross,MJ;Collen,D;Coller,BS
通讯作者: Coller,BS
使用血小板糖蛋白 IIb/IIIa 受体的新型肽拮抗剂预防犬股动脉中富含血小板的血栓再闭塞。
DOI: 10.1161/01.cir.80.6.1775
发表时间: 1989
期刊: Circulation
影响因子: 37.8
作者:
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通讯作者: Abendschein,DR