Van de Werf F, Ludbrook P A, Bergmann S R, Tiefenbrunn A J, Fox K A, de Geest H, Verstraete M, Collen D, Sobel B E
N Engl J Med. 1984 Mar 8;310(10):609-13. doi: 10.1056/NEJM198403083101001.
Tissue-type plasminogen activator is a naturally occurring, clot-selective activator of fibrinolysis. We recently reported that human tissue-type plasminogen activator isolated from a Bowes-melanoma-tissue-culture supernate lysed coronary thrombi in dogs without depleting circulating fibrinogen or alpha 2-antiplasmin, in contrast to the case with streptokinase and urokinase. In the present study coronary thrombolysis, confirmed angiographically, was induced within 19 to 50 minutes with intravenous or intracoronary tissue-type plasminogen activator in six of seven patients with evolving myocardial infarction. Circulating fibrinogen, plasminogen, and alpha 2-antiplasmin were not depleted by this agent, in contrast to the case in the two patients subsequently given streptokinase. In the one patient in whom lysis was not inducible with tissue-type plasminogen activator, it was also not inducible with streptokinase. These observations indicate that clot-selective coronary thrombolysis can be induced in patients with evolving myocardial infarction by means of tissue-type plasminogen activator, without concomitant induction of a systemic lytic state. Definition of its therapeutic benefit must await greater availability of the agent and the performance of appropriate clinical trials.
组织型纤溶酶原激活剂是一种天然存在的、具有凝块选择性的纤溶激活剂。我们最近报告称，从鲍伊斯黑色素瘤组织培养上清液中分离出的人组织型纤溶酶原激活剂可溶解犬的冠状动脉血栓，而不会消耗循环纤维蛋白原或α2-抗纤溶酶，这与链激酶和尿激酶的情况不同。在本研究中，7例进展性心肌梗死患者中有6例在静脉内或冠状动脉内给予组织型纤溶酶原激活剂后19至50分钟内，经血管造影证实诱导了冠状动脉溶栓。与随后给予链激酶的2例患者不同，该药物未消耗循环纤维蛋白原、纤溶酶原和α2-抗纤溶酶。在1例不能用组织型纤溶酶原激活剂诱导溶解的患者中，也不能用链激酶诱导溶解。这些观察结果表明，通过组织型纤溶酶原激活剂可在进展性心肌梗死患者中诱导凝块选择性冠状动脉溶栓，而不会同时诱导全身性溶解状态。其治疗益处的定义必须等待该药物更广泛的应用和适当临床试验的开展。
