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)

In the course of a study (now including 53 patients) on the effectiveness of urokinase in the treatment of acute coronary occlusion, coronary angiography was performed in 2 patients before and after the use of this drug. In both instances the angiograms demonstrated obstruction in the coronary-artery branches, with additional narrowing and some collateral circulation. After urokinase therapy, blood flow was restored in the areas previously obstructed. These 2 case reports are presented because they demonstrate this favorable change in coronary blood flow in association with this particular form of therapy. It is hoped that the completed urokinase study may add some information concerning the effect of thrombolysis in the management of myocardial infarction.
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PMID:The use of urokinase in acute myocardial infarction: report of two cases. 115 Oct 39

Despite enormous advances made in understanding of the biochemistry of fibrinolytic agents and their extensive clinical use in acute myocardial infarction a number of unresolved issues remain. There is an intriguing divergence of left ventricular response and reduction of mortality in patients with acute myocardial infarction treated with thrombolytic drugs. It is also difficult to explain why patients treated late have a reduced mortality after thrombolytic treatment. Uncertainty prevails on the validity of thrombolysis in patients with a low and very high risk of mortality. Resistance of coronary occlusion to any thrombolytic is another unexplained fact. Alteplase and saruplase are more fibrin-specific thrombolytic drugs than anistreplase. These and the thrombolytic drugs of the first generation (streptokinase and urokinase) have shortcomings and limitations. It is being explored whether prolonged intravenous maintenance infusions are more effective if replaced by a bolus injection, accelerated infusion or the combined intravenous administration of thrombolytic agents.
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PMID:Unresolved issues in the thrombolytic treatment of myocardial infarction. 178 46

Percutaneous transluminal coronary angioplasty was complicated by acute coronary occlusion, dissection of the arterial wall, or angiographic evidence of intraluminal thrombosis in 33 high-risk patients from 153 consecutive angioplasty procedures (21.5%). Ten patients (group I) were managed with nitroglycerin (0.2 to 0.4 mg i.c.) and repeated attempts at mechanical guide wire recanalization or dilation, but they did not receive thrombolytic therapy. In the remaining 23 patients (group II), intracoronary urokinase (100,000 to 360,000 U.I.) was administered over 15-20 min after onset of coronary occlusion or thrombosis and continued during attempts at repeated dilation of the stenosis. The incidence of sudden coronary artery occlusion was 70% in group I patients and 52% in group II. The angiographic evidence of thrombus formation was observed in a higher, but not significant, proportion of group II patients (65%) as compared with group I (30%). The incidence of intimal tearing or dissection was similar in the two groups of patients (40 vs. 34.7%). The overall final success rate of the complicated angioplasty series was 48% (6/33). However, the success rate was lower (10%) in group I than in group II patients (10 vs. 65%; P less than 0.005), and the frequency of emergency coronary artery bypass grafting was lower in group II patients (13 vs. 60%; P = 0.01), suggesting that thrombolytic therapy with urokinase may be effective in the management of acute coronary occlusion and thromboembolic complications of coronary angioplasty.
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PMID:Management of complicated coronary angioplasty by intracoronary urokinase and immediate re-angioplasty. 210 94

A 45-year-old man with unstable angina developed persistent ECG changes of myocardial ischemia during coronary angiography. Occlusion of the left anterior descending branch (LAD) was documented 20 minutes after these changes. Intracoronary nitrate, Ca antagonist, urokinase, removal by percutaneous transluminal coronary angioplasty (PTCA) of atherosclerotic obstructions, and emergency bypass surgery failed to restore myocardial perfusion. Only short periods of reflow were obtained by urokinase and PTCA. The repeated coronary injections demonstrated a progressive disappearance of the left anterior descending artery (LAD) starting from the distal portion and progressing retrogradely up to the origin of the vessel. The patient developed a transmural anterolateral myocardial infarction and 12 months later underwent cardiac transplantation for untractable failure. His heart was examined and the infarct confirmed. Analysis of this case suggests that coronary occlusion in acute myocardial infarction can be an event secondary to increased intramyocardial resistance rather than the cause of reduced coronary blood flow in subepicardial coronary arteries.
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PMID:Coronary occlusion: cause or consequence of acute myocardial infarction? 229 57

A case of coronary occlusion occurred seven days after successful percutaneous transluminal coronary angioplasty. The acute complication occurred shortly after a negative exercise stress test and was resolved with intracoronary urokinase.
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PMID:Acute coronary occlusion after recent coronary angioplasty. Association with exercise and successful treatment with intracoronary thrombolysis. 237 92

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)
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PMID:Coronary thrombolysis with recombinant single-chain urokinase-type plasminogen activator in patients with acute myocardial infarction. 242 83

For decades management of acute myocardial infarction (AMI) consisted of bed rest, oxygen, prevention for thromboembolic complications, and treatment of arrhythmias and heart failure. In the last years a more aggressive treatment of AMI has been developed, based on the following three basic principles: (1) Mortality of patients with AMI is determined by the infarct size and the degree of left ventricular dysfunction. (2) The time interval between the onset of coronary occlusion and any intervention to limit infarct size is brief and takes usually not more than three to four hours. (3) After the acute phase of infarction a lot of patients remain at high risk of fatal coronary events, i.e. reinfarctions. The angiographic findings during the first hours of AMI showed in about 80% of patients an obstructive coronary thrombus and led to efforts to dissolve the offending thrombi. The demonstration that coronary thrombi can be lysed in about 80% of cases within 60 minutes after the intracoronary injection of thrombolytic agents (streptokinase or urokinase) has boosted the reperfusion therapy in AMI in the hope that ischemic myocardium might be salvaged. Intracoronary infusion of thrombolytic agents however, can be applied only in a minority of patients with AMI because coronary angiography and a skilled team of investigators are required, therefore a short-time intravenous high dose streptokinase infusion was developed. In the meantime two large double blind randomized trials (ISAM and GISSI) could demonstrate a reduction in hospital mortality in AMI especially by early treatment with intravenous streptokinase. Conventional thrombolytic agents produce a systemic lytic state with the possibility of hemorrhage, therefore recombinant tissuetype plasminogen activator (rt-PA) and two other drugs, acylated streptokinase and pro-urokinase, were developed with the aim of inducing coronary thrombolysis without severe systemic lytic state, but the efficacy of these new drugs remains to be demonstrated in randomized trials versus conventional thrombolytic agents.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The therapy of acute myocardial infarction: current state of the art. 244 99

Recognition that myocardial infarction is caused by coronary thrombosis has stimulated a search for a safe, rapidly acting, and effective thrombolytic regimen. Tissue plasminogen activator (t-PA) can provide relatively clot-selective thrombolysis, but one quarter of patients fail to achieve reperfusion, lysis speed is not optimal, and higher doses have been associated with an increased incidence of hemorrhagic stroke. We report the results of a multicenter study of pro-urokinase, a second naturally occurring plasminogen activator that has structural similarities to t-PA but has a different mechanism of action. Pro-urokinase was administered 3.9 +/- 1.1 hours after the onset of chest pain to 40 patients with acute myocardial infarction with angiographically confirmed complete coronary occlusion (TIMI grade 0). After a 90-minute intravenous infusion of pro-urokinase (4.7-9 million units, 36-69 mg) 51% (20 of 39) of the patients demonstrated reperfusion (TIMI grade 2 or 3) occurring 64.8 +/- 22.3 minutes after initiation of therapy. Fibrinogen levels fell only 10 +/- 17% from baseline, confirming the fibrin specificity of pro-urokinase. As with t-PA, however, this specificity was only relative. alpha 2-Antiplasmin decreased to 39% and plasminogen decreased to 64% of initial values. Fibrinogen degradation products increased 63% and the fibrin-specific D-dimer increased 8.7-fold. Thus, pro-urokinase produces relatively clot-selective coronary thrombolysis similar to that produced by t-PA, but the use of either pro-urokinase or t-PA alone in higher doses would be likely to produce more nonspecific effects.
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PMID:Clot-selective coronary thrombolysis with pro-urokinase. 249 4

A 29-year-old heavy smoker presented with an acute myocardial infarction and hematocrit of 70%. At immediate coronary angiography a complete occlusion of the right coronary artery was found. After intracoronary urokinase the coronary arteries were found to be completely normal. Causes for the erythrocytosis other than smoking could be excluded. We conclude that thrombotic coronary occlusion with acute myocardial infarction was caused by erythrocytosis due to heavy smoking.
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PMID:[Acute myocardial infarct caused by nicotine-induced erythrocytosis]. 261 89

Pro-urokinase is a fibrin-specific, single-chain, high molecular form of urokinase that induces thrombolysis without fibrinogenolysis in experimental animals. Consequently, the potential advantage of pro-urokinase is that its activation can be limited to the site of a clot. Its efficiency was assessed in ten patients with acute transmural myocardial infarction. Reperfusion occurred in only two patients. In five out of seven patients with persistent complete coronary occlusion, clot lysis could be achieved by intracoronary streptokinase application within 30 min after completion of the pro-urokinase infusion. Fibrinogen and alpha 2-antiplasmin changed only moderately during pro-urokinase infusion. These preliminary data may indicate a limited thrombolytic efficiency of pro-urokinase in patients with acute myocardial infarction.
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PMID:[Initial experiences with pro-urokinase in acute myocardial infarct]. 312 30


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