Coronary thrombolysis with clot-selective plasminogen activators

Coronary thrombolysis is at present intensively investigated in the treatment of acute myocardial infarction. One line of research focuses on the development of new, fibrin-specific agents which might induce more clot-selective thrombolysis than streptokinase and urokinase. Clot-selective thrombolytic agents preferentially activate fibrin-bound plasminogen and, thereby, minimize the generation of free circulating plasmin which is responsible for the hemostatic breakdown and bleeding risk. Intravenous administration of fibrin-specific thrombolytic agents has two major advantages over intracoronary administration: firstly, infusion is more easily and widely applicable and secondly, therapy may be initiated more rapidly, which is important for the early restoration of nutritional blood flow and salvage of functional myocardial tissue. Three clot-selective thrombolytic agents are presently investigated for coronary thrombolysis. Impressive reopening rates have been reported with acylated streptokinase-plasminogen complex, but unfortunately, its use was associated with extensive systemic fibrinolytic activation and bleeding complications. Pro-urokinase, the single chain precursor of urokinase, exhibited intrinsic, fibrin-specific thrombolytic activity in vitro and in animal models but no human trials have yet been reported. At present, the largest clinical experience has been obtained with tissue-type plasminogen activator (t-PA). After small-scale pilot studies with t-PA obtained from cell culture media, larger clinical trials have now been performed using t-PA obtained by recombinant DNA technology (rt-PA). In the first study, intravenous infusion of rt-PA in patients with acute myocardial infarction yielded a recanalization rate of about 75% without clinically relevant systemic activation of the fibrinolytic system in most patients.(ABSTRACT TRUNCATED AT 250 WORDS)