Strony J, Song A, Rusterholtz L, Adelman B
Department of Medicine, Case Western Reserve University Hospital, Cleveland, OH 44106, USA.
Arterioscler Thromb Vasc Biol. 1995 Mar;15(3):359-66. doi: 10.1161/01.atv.15.3.359.
Acute rethrombosis following thrombolytic therapy occurs in 5% to 25% of patients. We evaluated the effect of aurintricarboxylic acid (ATA), a triphenyl dye that blocks von Willebrand factor (vWF) binding to platelet glycoprotein Ib, on arterial reperfusion and acute rethrombosis following fibrinolytic therapy. Primary thrombosis was induced in the femoral arteries of anesthetized dogs by application of anodal current and partial arterial constriction. Blood flow was monitored with an electromagnetic flow probe, and primary thrombosis was considered to have occurred when blood flow was reduced to and remained at zero. Reperfusion was induced by intravenous streptokinase 30 minutes after thrombosis. Streptokinase reduced plasma fibrinogen levels from an average of 144 mg/dL to < 5 mg/dL resulting in inhibition of ADP- and epinephrine-induced platelet aggregation ex vivo. Acute rethrombosis following reperfusion occurred within 37 +/- 18 (mean +/- SD) minutes in 89% (16/18) of animals receiving thrombolytic activator treatment. Histological examination of reoccluding thrombi revealed densely aggregated platelets and erythrocytes with no detectable fibrin. In the two other study groups, ATA was infused in conjunction with thrombolytic therapy (10 arteries) or at near completion of acute rethrombosis following fibrinolytic activator treatment (6 arteries). In each case ATA prevented rethrombosis. However, concomitant administration of ATA and thrombolytic therapy delayed restoration of blood flow. ATA had no direct effect on hemodynamics, thrombin time, platelet count, or platelet aggregation response to ADP, epinephrine, or collagen. These data indicate that inhibition of vWF-platelet glycoprotein Ib interaction is effective in preventing acute rethrombosis following thrombolytic therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
溶栓治疗后急性再血栓形成发生在5%至25%的患者中。我们评估了金精三羧酸（ATA）的作用，ATA是一种三苯基染料，可阻断血管性血友病因子（vWF）与血小板糖蛋白Ib的结合，观察其对纤溶治疗后动脉再灌注和急性再血栓形成的影响。在麻醉犬的股动脉中，通过施加阳极电流和局部动脉收缩诱导原发性血栓形成。用电磁流量探头监测血流，当血流降至并维持在零时，认为原发性血栓形成。血栓形成30分钟后，通过静脉注射链激酶诱导再灌注。链激酶使血浆纤维蛋白原水平从平均144mg/dL降至<5mg/dL，导致体外ADP和肾上腺素诱导的血小板聚集受到抑制。接受溶栓激活剂治疗的动物中，89%（16/18）在再灌注后37±18（平均值±标准差）分钟内发生急性再血栓形成。对再闭塞血栓的组织学检查显示，血小板和红细胞密集聚集，未检测到纤维蛋白。在另外两个研究组中，ATA与溶栓治疗联合输注（10条动脉）或在纤溶激活剂治疗后急性再血栓形成接近完成时输注（6条动脉）。在每种情况下，ATA都可预防再血栓形成。然而，ATA与溶栓治疗同时给药会延迟血流恢复。ATA对血流动力学、凝血酶时间、血小板计数或血小板对ADP、肾上腺素或胶原的聚集反应无直接影响。这些数据表明，抑制vWF-血小板糖蛋白Ib相互作用可有效预防溶栓治疗后的急性再血栓形成。（摘要截短至250字）
