Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.73 (urokinase-type plasminogen activator)
 10,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pro-urokinase is a single chain precursor of two chain urokinase, which has been shown to induce fibrin-selective plasminogen activation. In the present study, thrombolytic efficacy of 9 million U of glycosylated pro-urokinase administered intravenously was compared with that of a combined regimen utilizing 4.5 million U of pro-urokinase and 0.2 million U of urokinase. Seventy-five patients with a first myocardial infarction were randomized to receive high dose pro-urokinase (n = 40, group A) or the combination therapy (n = 35, group B). Reperfusion of the infarct-related artery was assessed by repeat coronary angiography. Thrombolysis in Myocardial Infarction trial (TIMI) grade II or III reperfusion was achieved in 73% of group A patients compared with 66% of group B patients (p = NS). A trend toward faster reopening of the infarct-related artery was observed in patients in group B. Coronary artery reocclusion occurred in 5 (10%) of 49 patients in whom angiography was repeated within 36 h after the start of therapy. Clot-selective thrombolysis was indicated by a minimal fibrinogen decline (15% and 13%, respectively, in groups A and B). Alpha 2-antiplasmin levels, however, decreased more rapidly in patients in group B (p less than 0.05). This finding and the equivalent reperfusion rate in the combined treatment group strongly suggest synergistic interaction between these two thrombolytic agents. In summary, the high incidence of reperfusion, the low rate of early reocclusion and the paucity of side effects, particularly with regard to bleeding complications, indicate that pro-urokinase possesses the characteristics of an ideal thrombolytic agent.
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PMID:Coronary reperfusion studies with pro-urokinase in acute myocardial infarction: evidence for synergism of low dose urokinase. 211 22

The thrombolytic efficacy of recombinant unglycosylated full length single chain urokinase-type plasminogen activator (rscu-PA, saruplase), applied either as single intravenous bolus or as a continuous infusion over 60 minutes, was studied in 5 randomized blinded groups of 5 dogs with combined copper coil induced coronary artery thrombosis and 125I-fibrin labeled femoral vein clots. Infusion of 1 mg/kg recu-PA (group I) induced coronary recanalization in 4 of 5 dogs and 98 +/- 1% (mean +/- SEM) venous clot lysis. Bolus injection of 1 mg/kg recu-PA (group II) caused reflow in 3 of 5 dogs and 88 +/- 5 percent venous clot lysis. Infusion of 0.5 mg/kg rescu-PA (group III) achieved reflow in 3 of 5 dogs and 52 +/- 6% venous clot lysis. Bolus injection of 0.5 mg/kg rscu-PA (group IV) induced reflow in 4 of 5 dogs and 48 +/- 12% venous clot lysis. Placebo infusion (group V) was associated with late recanalization in 1 of 5 dogs and 18 +/- 8% venous clot lysis. Coronary artery reocclusion after reflow was not observed in groups I and II, but occurred in 2 of 3 animals in group III and in 3 of 4 animals in group IV (P = .02). The time to reflow in responsive animals was 22 +/- 5 minutes with infusion of 0.5 or 1 mg/kg rscu-PA and 14 +/- 1 minute with bolus injection of 0.5 or 1 mg/kg (P = .14). Depletion of fibrinogen and alpha 2-antiplasmin to less than 25% of baseline levels was observed in the 5 dogs given 1 mg/kg rscu-PA by bolus and in 3 of the 5 dogs given 1 mg/kg rscu-PA via infusion, but in none of the dogs that received 0.5 mg/kg rscu-PA (P less than .001). Plasma clearance rates were 170 +/- 44 and 230 +/- 30 mL/minute after bolus injection and 190 +/- 47 and 310 +/- 56 mL/minute during infusion of rscu-PA for the 1 mg/kg and 0.5 mg/kg doses respectively. Thus, intravenous bolus injection of rscu-PA (saruplase) appears to be equipotent to an infusion over 60 minutes for both coronary and venous thrombolysis. This animal model of combined arterial and venous thrombolysis may be useful for the evaluation of new thrombolytic strategies.
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PMID:Comparison of intravenous bolus injection or continuous infusion of recombinant single chain urokinase-type plasminogen activator (saruplase) for thrombolysis. A canine model of combined coronary arterial and femoral venous thrombosis. 211 30