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Coronary thrombolysis with recombinant single-chain urokinase-type plasminogen activator in patients with acute
Insights
Recombinant single-chain urokinase-type plasminogen activator (scu-PA) effectively achieved coronary recanalization in acute myocardial infarction patients. Higher doses of scu-PA improved vessel patency and distal filling, with no significant side effects observed.
Area of Science:
- Cardiology
- Biochemistry
- Pharmacology
Background:
- Acute transmural myocardial infarction involves complete coronary artery occlusion.
- Thrombolytic therapy aims to restore blood flow in occluded coronary arteries.
Purpose of the Study:
- To evaluate the efficacy and safety of recombinant single-chain urokinase-type plasminogen activator (rscu-PA) in patients with acute myocardial infarction.
- To determine optimal dosing for recanalization and vessel patency.
Main Methods:
- Seventeen patients with acute myocardial infarction and coronary occlusion received heparin plus intravenous rscu-PA.
- Two dosing regimens were tested: 10 mg bolus + 30 mg/hr (8 patients) and 10 mg bolus + 60 mg/hr (9 patients).
- Coronary recanalization, plasma rscu-PA levels, and markers of fibrinolysis (alpha 2-antiplasmin, fibrinogen, FDPs) were monitored.
Main Results:
- The higher dose regimen (10 mg + 60 mg/hr) resulted in recanalization with normal distal filling in 7 out of 9 patients within 46 minutes.
- The lower dose regimen (10 mg + 30 mg/hr) achieved recanalization in 6 out of 8 patients, but with persistent delayed opacification in four.
- Biochemical markers showed dose-dependent effects on fibrinolysis, with greater inhibition of alpha 2-antiplasmin and fibrinogen at the higher rscu-PA dose.
- No significant bleeding or short-term side effects were reported for either dose.
Conclusions:
- Recombinant scu-PA is an effective thrombolytic agent for acute myocardial infarction.
- A higher infusion dose of rscu-PA (60 mg/hr) leads to better recanalization and vessel patency compared to a lower dose (30 mg/hr).
- rscu-PA demonstrates a favorable safety profile in this patient cohort.
Abstract:
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)