Cercek B, Lew A S, Hod H, Yano J, Reddy N K, Ganz W
Circulation. 1986 Sep;74(3):583-7. doi: 10.1161/01.cir.74.3.583.
The effect of pretreatment with heparin on lysis of arterial thrombi by tissue-type plasminogen activator (rt-PA) was studied in 19 dogs. Copper coil-induced carotid artery thrombi were weighed, inserted into the femoral arteries, and exposed to a 15 min infusion of rt-PA at 10 micrograms/kg/min either with (n = 6 thrombi) or without pretreatment with a 200 unit/kg bolus of heparin (n = 6 thrombi). The infusion of rt-PA without pretreatment reduced the thrombus weight by 27.6 +/- 7.4%, while infusion of rt-PA with pretreatment reduced it by 79.1 +/- 12.3% (p less than .0001). To test the hypothesis that heparin enhanced thrombolysis by preventing continued incorporation of new fibrin into the thrombus during thrombolysis we repeated the experiments using pretreatment with 8 U/kg of ancrod, which rapidly depletes fibrinogen. Pretreatment with ancrod (n = 6 thrombi) depleted fibrinogen and enhanced the lytic effect of rt-PA to a similar degree as pretreatment with heparin, resulting in a 67.6 +/- 12.3% (NS) decrease in thrombus weight. We conclude that heparin significantly enhances the thrombolytic effect of rt-PA, probably by preventing new fibrin formation and its incorporation into the thrombus during lysis.
在19只犬中研究了肝素预处理对组织型纤溶酶原激活剂（rt-PA）溶解动脉血栓的作用。将铜圈诱导形成的颈动脉血栓称重后，插入股动脉，然后以10微克/千克/分钟的速度输注rt-PA 15分钟，其中6个血栓在输注前给予200单位/千克的肝素推注进行预处理，另外6个血栓则不进行预处理。未预处理而输注rt-PA使血栓重量减少了27.6±7.4%，而预处理后输注rt-PA则使其减少了79.1±12.3%（p＜0.0001）。为了检验肝素通过在溶栓过程中防止新的纤维蛋白持续掺入血栓而增强溶栓作用这一假说，我们重复了实验，使用8单位/千克的抗栓酶进行预处理，抗栓酶可迅速消耗纤维蛋白原。用抗栓酶预处理（6个血栓）使纤维蛋白原消耗，并使rt-PA的溶解作用增强到与肝素预处理相似的程度，导致血栓重量下降67.6±12.3%（无显著性差异）。我们得出结论，肝素可能通过在溶解过程中防止新的纤维蛋白形成及其掺入血栓，从而显著增强rt-PA的溶栓作用。
