Coronary thrombolysis with recombinant staphylokinase in patients with evolving myocardial infarction.
BACKGROUND Staphylokinase (STA), a protein with known profibrinolytic properties, is produced by transduced Staphylococcus aureus strains. In experimental animal models, recombinant staphylokinase (STAR) is less immunogenic and more active toward platelet-rich arterial blood clots than streptokinase.
METHODS AND RESULTS In the present study, 10 mg STAR given intravenously over 30 minutes was found to induce angiographically documented coronary artery recanalization within 40 minutes in four of five patients with acute myocardial infarction. Plasma fibrinogen and alpha 2-antiplasmin levels were unaffected, and allergic reactions were not observed. Postinfusion disappearance of STAR antigen followed a biphasic mode with a t1/2 alpha of 6.3 +/- 0.6 minutes (mean +/- SD) and a t1/2 beta of 37 +/- 15 minutes, corresponding to a plasma clearance of 270 +/- 100 mL/min. Neutralizing antibodies against STAR could not be demonstrated at baseline and up to 6 days after infusion, but STAR neutralizing activity, which did not cross-react with streptokinase, was consistently demonstrable in plasma at 14-35 days.
CONCLUSIONS STAR can induce clot-selective coronary thrombolysis in patients with evolving myocardial infarction without concomitant induction of a systemic lytic state. STAR, a small protein that can be easily produced by recombinant DNA technology, may therefore offer promise for thrombolytic therapy in patients with thromboembolic disease.
- Copyright © 1993 by American Heart Association