Stroughton J, Ouriel K, Shortell C K, Cho J S, Marder V J
Department of Surgery, University of Rochester, NY 14642.
J Vasc Surg. 1994 Feb;19(2):298-303; discussion 303-5. doi: 10.1016/s0741-5214(94)70105-9.
A relative deficiency of plasminogen within the thrombus may be the rate limiting factor in clot lysis.
To investigate this hypothesis, we used an in vitro perfusion system and expanded polytetrafluoroethylene graft segments filled with radiolabeled human thrombus. Three groups of five perfusions were compared: (1) urokinase infusion (333 IU/min) into clots laced with buffer, (2) urokinase infusion (333 IU/min) into clots laced with plasminogen (44 CU), and (3) control, D5W infusion into clots laced with buffer. Two end points were measured over time: the amount of lysed thrombus and the flow through the graft.
Urokinase infusion resulted in augmented flow through the graft when compared with control (p < 0.05). Lacing with plasminogen resulted in more rapid restoration of flow when compared with urokinase infusion alone (p < 0.05). Similarly, the rate of clot dissolution was significantly greater in plasminogen-laced thrombi (p < 0.05) when compared with the control and urokinase groups. Embolization of particles of thrombus was uniformly observed in the urokinase group, resulting in a temporary decrease in flow through the thrombosed graft. This event characteristically occurred after 60 minutes of infusion but was never seen in the urokinase/plasminogen treatment group.
These results suggest that plasminogen supplementation of urokinase thrombolysis may result in significant clinical benefits with respect to the rate of clot lysis and the uniformity of clot dissolution with a lower likelihood of secondary embolization.
血栓内纤溶酶原相对缺乏可能是凝块溶解的限速因素。
为研究这一假设，我们使用体外灌注系统和填充有放射性标记人血栓的膨体聚四氟乙烯移植段。比较了三组，每组进行五次灌注：（1）向用缓冲液处理的凝块中注入尿激酶（333 IU/分钟）；（2）向用纤溶酶原（44 CU）处理的凝块中注入尿激酶（333 IU/分钟）；（3）对照组，向用缓冲液处理的凝块中注入5%葡萄糖注射液。随着时间推移测量两个终点指标：溶解的血栓量和通过移植段的血流量。
与对照组相比，注入尿激酶后通过移植段的血流量增加（p < 0.05）。与单独注入尿激酶相比，用纤溶酶原处理能使血流量恢复得更快（p < 0.05）。同样，与对照组和尿激酶组相比，用纤溶酶原处理的血栓的溶解速率显著更高（p < 0.05）。在尿激酶组中均观察到血栓颗粒的栓塞，导致通过血栓形成的移植段的血流量暂时下降。这一情况通常在注入60分钟后发生，但在尿激酶/纤溶酶原治疗组中从未出现。
这些结果表明，在尿激酶溶栓治疗中补充纤溶酶原可能在凝块溶解速率、凝块溶解的均匀性方面带来显著的临床益处，且二次栓塞的可能性更低。
