Helft G, Elalamy I, Beygui F, Dambrin G, Lecompte T, Le Pailleur C, Le Feuvre C, Metzger J P, Vacheron A, Samama M M
Clinique cardiologique, hôpital Necker, Paris.
Arch Mal Coeur Vaiss. 1999 Apr;92(4):411-7.
Myocardial infarction is the result of thrombotic coronary artery occlusion. Although present-day thrombolytics have major value by increasing the frequency of reopening of arteries responsible for myocardial infarction, by preserving myocardial function and, thereby, significantly reduce mortality. Nevertheless, they are subject to the following limitations: 1) excellent arterial partency is only obtained in 50% of cases: 2) reocclusion occurs in 5 to 10% of cases; 3) severe complications such as cerebral haemorrhage are observed in about 0.5% of cases. Therefore, the search to improve thrombolytic agents is intense. This article reports the recent advances in concept and production of new thrombolytic agents. The most recent results concern the production of mutants of T-PA (tissue plasmogen activator). Of these mutants, the reteplase (r-PA) has already received authorization for its commercialisation. Other t-PA mutants under development (phase 3) include TNK-t-PA and lanoteplase. Over the last few years, there has been renewed interest in staphylokinase. The results of the initial clinical trials with this agent have also been reported. Paradoxically, the mode of action of thrombolytic agents has an inherent pro-thrombotic effect. This explains some of the interest for anti-thrombotic agents as an adjuvant treatment of thrombolysis. The initial results of the association of thrombolytics with new glycoprotein IIb/IIIa platelet inhibitors and anti-thrombin agents are reported.
心肌梗死是冠状动脉血栓形成阻塞的结果。尽管当今的溶栓剂通过增加导致心肌梗死的动脉再通频率、保护心肌功能从而显著降低死亡率而具有重要价值。然而,它们存在以下局限性:1)仅50%的病例能实现良好的动脉通畅;2)5%至10%的病例会发生再闭塞;3)约0.5%的病例会出现严重并发症,如脑出血。因此,对改进溶栓剂的研究十分激烈。本文报道了新型溶栓剂在概念和生产方面的最新进展。最新成果涉及组织型纤溶酶原激活剂(T-PA)突变体的生产。在这些突变体中,瑞替普酶(r-PA)已获得商业化授权。其他正在研发(3期)的T-PA突变体包括替奈普酶(TNK-t-PA)和拉诺替普酶。在过去几年中,对葡萄球菌激酶重新产生了兴趣。也报道了该药物初步临床试验的结果。矛盾的是,溶栓剂的作用方式具有内在的促血栓形成作用。这解释了将抗血栓药物作为溶栓辅助治疗的部分原因。报道了溶栓剂与新型糖蛋白IIb/IIIa血小板抑制剂及抗凝血酶药物联合使用的初步结果。