Gulba D C, Fischer K, Barthels M, Polensky U, Reil G H, Daniel W G, Welzel D, Lichtlen P R
Cardiology Department, Hannover Medical School, Federal Republic of Germany.
Am J Cardiol. 1989 May 1;63(15):1025-31. doi: 10.1016/0002-9149(89)90072-6.
By inducing minimal free-fibrinolytic activity with low dose urokinase, the lag phase of prourokinase can be overcome, and the rate of thrombolysis with this substance can be strongly enhanced. The thrombolytic potency of a combination of 250,000 IU of urokinase and 2 doses of prourokinase (4.5 or 6.5 megaunits) was evaluated in an open-label, nonrandomized dose-finding study. Thirty-one patients participated. With 4.5 megaunits of prourokinase (group 1, 15 patients) patency was demonstrated angiographically at 60 minutes in 33% while with 6.5 megaunits (group II, 16 patients) 75% patency was achieved (p less than 0.01). A second angiogram recorded 24 to 36 hours after thrombolysis revealed reocclusion in 60 versus 8% of primarily patent coronary arteries (p less than 0.05). Hemostatic monitoring in both groups revealed only slight to moderate consumption of fibrinogen (-9 vs -13%), plasminogen (-29 vs -34%) and alpha 2-antiplasmin (-59 vs -63%), and an increase in D-dimers, the split products of cross-linked fibrin, to a maximum of 1.008 +/- 1.211 vs 0.547 +/- 0.684 micrograms/liter. None of these differences was significant. Bleeding complications were more frequently observed in group II (13 vs 37%) (difference not significant), but were mild and related to puncture sites, except in 1 patient with mild oozing from the gum. No major hemorrhage was observed. These results suggest that low dose urokinase preactivation enhances the thrombolytic potency of prourokinase, without affecting its high fibrin specificity. Compared to previous studies using only prourokinase, low dose urokinase preactivation reduces by 50% the prourokinase dose as required for effective thrombolysis.(ABSTRACT TRUNCATED AT 250 WORDS)
通过用低剂量尿激酶诱导最小的游离纤维蛋白溶解活性，可以克服纤溶酶原激活剂的延迟期，并能显著提高该物质的溶栓速率。在一项开放标签、非随机剂量探索性研究中，评估了250,000国际单位尿激酶与2剂纤溶酶原激活剂（450万或650万单位）联合使用的溶栓效力。31名患者参与了研究。使用450万单位纤溶酶原激活剂的患者（第1组，15名患者）在60分钟时血管造影显示血管通畅率为33%，而使用650万单位的患者（第II组，16名患者）血管通畅率达到75%（p<0.01）。溶栓后24至36小时记录的第二次血管造影显示，主要通畅的冠状动脉中，再闭塞率分别为60%和8%（p<0.05）。两组的止血监测仅显示纤维蛋白原（-9%对-13%）、纤溶酶原（-29%对-34%）和α2-抗纤溶酶（-59%对-63%）有轻微至中度消耗，以及交联纤维蛋白的裂解产物D-二聚体增加，最高分别达到1.008±1.211与0.547±0.684微克/升。这些差异均无统计学意义。第II组更频繁地观察到出血并发症（13%对37%）（差异无统计学意义），但均为轻度且与穿刺部位有关，除1名患者牙龈有轻度渗血外。未观察到严重出血。这些结果表明，低剂量尿激酶预激活可增强纤溶酶原激活剂的溶栓效力，而不影响其高纤维蛋白特异性。与以往仅使用纤溶酶原激活剂的研究相比，低剂量尿激酶预激活可将有效溶栓所需的纤溶酶原激活剂剂量减少50%。（摘要截取自250字）
