Coronary thrombolysis with recombinant single-chain urokinase-type plasminogen activator in patients with acute myocardial infarction.
Seventeen patients with acute transmural myocardial infarction and angiographically confirmed complete coronary occlusion were treated with heparin combined with intravenous single-chain urokinase-type plasminogen activator (scu-PA), obtained by expression of the cDNA encoding mature human scu-PA in Escherichia coli. In eight patients, recombinant scu-PA (rscu-PA) was given as a 10 mg bolus followed by 30 mg over 1 hr. Recanalization was obtained in six patients, but with persistent delayed opacification of the vessel in four of these patients. During infusion, a plateau level of rscu-PA antigen in plasma of 3.4 micrograms/ml (median value, range 1.4 to 5.5) was reached. At the end of the infusion the alpha 2-antiplasmin level had decreased to 54% (median, range 22% to 82%) of the preinfusion level, the fibrinogen level to 89% (median, range 26% to 101%), and fibrinogen degradation products (FDPs) to 20 micrograms/ml (median, range 8 to 387). In nine patients, rscu-PA was administered as a 10 mg bolus followed by 60 mg over 1 hr. This resulted in recanalization with normal distal filling of the vessel in seven patients, within 46 +/- 17 min (mean +/- SD). During infusion the concentration of rscu-PA in plasma increased to a median value of 7.4 micrograms/ml (range 4.0 to 13.3). At the end of the infusion the alpha 2-antiplasmin level was 22% of baseline (range 5% to 47%), the fibrinogen level 45% (range 4% to 94%), and the concentration of FDPs 87 micrograms/ml (range 6 to 1034). No significant bleeding or short-term side effects were observed.(ABSTRACT TRUNCATED AT 250 WORDS)
D000328:Adult; D000368:Aged; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005340:Fibrinogen / Q000032:analysis; D006493:Heparin / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy*; D010865:Pilot Projects; D010960:Plasminogen Activators / Q000008:administration & dosage* / Q000009:adverse effects; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000009:adverse effects; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage* / Q000009:adverse effects; D000979:alpha-2-Antiplasmin / Q000032:analysis
D005338:Fibrin Fibrinogen Degradation Products; D011994:Recombinant Proteins; D000979:alpha-2-Antiplasmin; D005340:Fibrinogen; D006493:Heparin; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator