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)

Coronary arterial thrombolysis is becoming an established treatment of acute myocardial infarction. If given early enough, it recanalises occluded coronary arteries, salvages myocardial function and reduces mortality. A reduction of mortality in patients with acute myocardial infarction has now been demonstrated for streptokinase, anisoylated plasminogen streptokinase activator complex (APSAC; anistreplase) and recombinant tissue-type plasminogen activator (rt-PA). From the biochemical point of view, rt-PA has several attractive properties. It is similar to or identical with the physiological plasminogen activator in blood, it does not induce an antibody response, and it is more fibrin-specific than most or all other currently known thrombolytic agents. The rate of recanalisation of occluded coronary arteries with rt-PA is about 60 to 80% in non-comparative and placebo-controlled trials. rt-PA was similar in efficacy to urokinase in the only trial to compare the 2 agents. In 2 comparative trials evaluated by meta-analysis, rt-PA appeared more effective than streptokinase for the early recanalisation of occluded arteries. Both agents were comparable in their effects on left ventricular function in 2 comparative trials, but further study is needed to conclusively evaluate this parameter. Moreover, both agents reduce inhospital mortality, but much larger direct comparative trials are required before scientifically valid statements can be made on the relative clinical efficacy of available thrombolytic agents in terms of their effects on both morbidity and mortality. Thus, rt-PA constitutes a notable contribution of recombinant DNA technology to the treatment of thromboembolic disease, the main cause of death and disability in Western societies.
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PMID:Tissue-type plasminogen activator. A review of its pharmacology and therapeutic use as a thrombolytic agent. 250 90

The characteristics and efficacy of alteplase in treating acute myocardial infarction (AMI) are described, and the role of the pharmacist with respect to thrombolytic therapy is discussed. Most patients with AMI have an acute thrombotic occlusion in the coronary artery supplying the infarcted tissue. Subsequent mortality from AMI can be reduced if patients receive thrombolytic therapy within 4 to 24 hours after the onset of symptoms. Tissue-type plasminogen activator produced by recombinant DNA techniques (alteplase) is purported to be indistinguishable from the endogenous protein. When given intravenously, alteplase has a rapid onset of action and a half-life of three to nine minutes, producing plasma concentrations of plasminogen activator 1000 times greater than those seen under normal physiologic conditions. Because alteplase has an affinity for fibrin and is, therefore, clot specific, its use does not induce the systemic plasminogen activation seen with streptokinase or urokinase therapy. The major adverse effect of alteplase therapy is bleeding. Comparative studies have shown reperfusion rates of 66% to 75% with alteplase and of 36% to 76% with streptokinase. Alteplase has generally been more effective than streptokinase in initiating reperfusion. Alteplase may be used for treatment of reocclusion after initial treatment with either alteplase or streptokinase. Because alteplase costs approximately 30 times more than streptokinase, informed medical decision making is imperative. It is suggested that pharmacists develop protocols, monitor thrombolytic therapy in their institutions, stay informed about current research, regularly report their findings to medical colleagues, and provide information and education to physicians, nurses, and patients. The rational use of thrombolytic agents requires consideration of the attendant clinical and economic consequences.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Risks versus benefits: the alteplase experience. 251 14

Thirty-five patients greater than 70 years of age with acute myocardial infarction (AMI) were treated with emergency percutaneous transluminal coronary angioplasty (PTCA). Seventeen (49%) patients received previous thrombolytic therapy: streptokinase (10 patients), tissue plasminogen activator (6) and combined tissue plasminogen activator and urokinase (1). Infarct-related artery patency was achieved in 26 patients (74%) after PTCA. Total in-hospital mortality was 34%. Univariate analysis showed a higher in-hospital mortality in patients with an occluded vessel after PTCA (78%) than in those patients with a patient infarct-related artery (19%) (p = 0.003). Symptomatic coronary reocclusion occurred in 3 patients (15%) during the hospital stay. Compared with emergency PTCA in 200 consecutively treated patients less than 70 years of age, the in-hospital mortality was increased (34 vs 6%, p less than 0.001), and the primary success rate was reduced (66 vs 90%, p less than 0.001). At a mean follow-up of 28 months, there has been a 13% out-of-hospital mortality rate in the elderly patients (3 patients died). Of the 20 surviving patients, 14 are asymptomatic and 6 have class II angina. In conclusion, emergency PTCA for AMI in elderly patients is associated with a decreased success rate and a higher mortality rate. However, the in-hospital mortality rate is not dissimilar to that in elderly AMI patients treated with conventional therapy or thrombolytic therapy alone, and the postdischarge mortality rates are low.
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PMID:Emergency percutaneous transluminal coronary angioplasty during acute myocardial infarction for patients more than 70 years of age. 252 65

Thirty-six consecutive patients with evolving acute myocardial infarction underwent emergent coronary angiography and intracoronary thrombolysis with urokinase. Nineteen of the patients had had angina before the infarction (group A), whereas the infarction was unheralded in the remaining 17 (group B). Thirty-two vessels (88%) were patent at follow-up angiography performed after 3 to 4 weeks, and the residual stenosis was 87% +/- 14% in group A and 47% +/- 25% in group B (p less than 0.001). Coronary spasm was provoked by ergonovine maleate in four of 12 patients in group A (33%) and in three patients in group B (18%). Coronary revascularization was undertaken in nine patients in group A and three in group B. These results indicate that patients with angina preceding acute myocardial infarction are more likely to have significant stenosis even at the late follow-up stage and to have a more urgent need for subsequent coronary revascularization. It also seems apparent that thromboembolism in most patients and coronary spasm in a few patients without significant coronary narrowing play significant causal roles in the onset of acute myocardial infarction.
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PMID:Angina preceding myocardial infarction and residual coronary narrowing after intracoronary thrombolysis. 252 18

ACO occurred within 40 min (mean 15.7 min) after PTCA in 22 patients and more than 12 hours in 2. The group with ACO had a significantly higher incidence of female (46% vs 23%), acute myocardial infarction (63% vs 35%), eccentric lesions (73% vs 28%), tortuous lesions (30% vs 4%) and coronary dissection or intraluminal haziness (89% vs 34%). Luminal narrowing before and after PTCA was significantly higher in ACO group than in control group (93% and 56% vs 87% and 23%). Repeat PTCA was performed in 17 patients and was successful in 13. Coronary bypass surgery was performed in 4 patients. Intracoronary urokinase was ineffective to ACO. In 3 autopsy cases dying 5, 14 and 17 days after PTCA, large extent of intimal tears and thrombus in the space of tears and the lumens were observed. These results suggest that coronary dissection chiefly contributes to ACO and coronary thrombosis is superimposed for a secondary event in most of cases with ACO.
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PMID:[Clinicopathologic study of acute coronary occlusion in percutaneous transluminal coronary angioplasty]. 252 97

Different fibrinogen species were examined in normal plasma following urokinase treatment, in isolated high molecular weight fibrinogen treated with plasmin and in plasma samples from patients with acute myocardial infarction receiving thrombolytic therapy. In normal plasmas two main fibrinogen species (Mr = 340,000 and Mr = 320,000) and an intermediate fragment (Mr = 330,000) were observed. The 340,000 fibrinogen was the most sensitive to degradation; it gave rise to 330,000 and 320,000 species. Degradation of isolated 340,000 fibrinogen was similar to plasma fibrinogen degradation. After thrombolytic therapy in acute myocardial infarction patients, when the plasma fibrinogen decreased near to zero, the new synthesized fibrinogen was 340,000 form. 'In vivo' conversion of 340,000 to 320,000 fibrinogen, associated with the transitory 330,000 form, was observed. The coagulation study of plasma fibrinogen showed that when Mr 340,000 fibrinogen decreased (40%), the gelation rate decreased and lag time increased drastically. The high 340,000 fibrinogen content found in acute myocardial infarction patients gave rise to the hypercoagulable state.
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PMID:Human fibrinogen heterogeneity. A study of limited fibrinogen degradation. 253 81

In a prospective, double-blind, randomised trial, 401 patients with a first acute myocardial infarction were treated within 4 h of onset of symptoms with 80 mg recombinant pro-urokinase or single-chain urokinase plasminogen activator (rscu-PA; proposed INN saruplase) intravenously given as a 20 mg bolus followed by 60 mg infusion for 60 min (198 patients), or 1.5 million IU streptokinase infused over 60 min (203 patients). The first two angiograms were taken at 60 min and at 90 min. Angiography was repeated at 24-36 h. Patency rates at 60 min were 71.8% for rscu-PA and 48.0% for streptokinase (p less than 0.001) and at 90 min they were 71.2% and 63.9%, respectively (p = 0.15). At 24-36 h 6/121 patients treated with rscu-PA and 5/114 patients treated with streptokinase showed reocclusion of the vessel. At the end of the thrombolytic infusion (60 min) fibrinogen concentration had decreased to 0.44 (0.23-1.27) g/l (median, 1st and 3rd quartile) in patients treated with rscu-PA and to 0.17 (0.06-0.27) g/l in patients treated with streptokinase (p less than 0.001). Concentrations of fibrin(ogen) degradation products rose to 96 (24-240) mg/l after rscu-PA and to 240 (192-360) mg/l after streptokinase (p less than 0.001). Bleeding complications were less common in the rscu-PA than in the streptokinase group (p less than 0.01). Thus intravenous rscu-PA led to higher patency rate, earlier reperfusion, less disturbance of haemostasis, and fewer bleeding complications than did intravenous administration of streptokinase.
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PMID:Randomised double-blind trial of recombinant pro-urokinase against streptokinase in acute myocardial infarction. PRIMI Trial Study Group. 256 49

Emergency percutaneous transluminal coronary angioplasty (PTCA) was performed during an acute myocardial infarction (AMI) after either systemic or intracoronary thrombolytic therapy in six patients with severe ischaemic left ventricular dysfunction or cardiogenic shock, among 37 patients (17%) who were treated with PTCA during AMI over a 13-month period. Thrombolytic therapy with streptokinase (1.5 x 10 Units) was initiated after a mean (+/- SD) time delay of 5.5 +/- 1.3 h from the onset of symptoms. The infarct-related artery was found to be occluded (TIMI grade 0-1) in three patients and partially reperfused (TIMI grade 2) in the remaining patients at baseline coronary angiography. Intracoronary administration of urokinase (100-200,000 Units) was ineffective in those patients failing systemic thrombolysis and resulted in only a slight increase of residual lumen in three patients. The coronary artery could be opened by a guidewire mechanical technique in patients with persistent coronary artery occlusion and coronary dilation could be done in all patients. The mean percentage diameter stenosis of the infarct-related vessel was reduced from 98.8 +/- 2% to 27 +/- 11% (P less than 0.005). After the procedure, left ventricular ejection fraction increased from 27 +/- 8% to 41 +/- 7% (P less than 0.02), systemic blood pressure and cardiac index increased respectively from 86 +/- 10 to 126 +/- 14 mmHg (P less than 0.005) and from 2.2 +/- 0.6 to 3.3 +/- 0.6 (P less than 0.01). Left ventricular end-diastolic pressure decreased from 26 +/- 8 to 18 +/- 3 mmHg (P less than 0.05). Severe mitral regurgitation was relieved in one patient.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Emergency coronary angioplasty in patients with severe left ventricular dysfunction or cardiogenic shock after acute myocardial infarction. 259 97

A case of acute myocardial infarction due to the lesion in the left main coronary artery was reported. A 50-year male was referred to our department for suspected acute myocardial infarction. Physical examination on admission revealed slight cyanosis with cold sweating due to severe chest pain. Pulse was irregular and heart rate was 78 beats/min. Blood pressure was 100/80 mmHg. A series of electrocardiograms (ECG) and laboratory data provided the diagnosis of wide-ranged anterolateral infarction in the left ventricle. Emergency coronary angiograms taken without delay showed a subtotal occlusion (99% stenosis) of the left main coronary trunk (LMT) before the initiation of intracoronary thrombolysis (PTCR). Following the intracoronary infusion of urokinase of 1,200,000 units, symptoms and ECG changes transiently improved but worsened later, and LMT stenotic lesion and delayed filling of myocardium were similar with before PTCR. Emergency coronary-aorto bypass graft (CABG) was undertaken without a significant delay to both the left anterior descending artery (LAD) and left circumflex coronary artery (LCX). With these treatments, the patient could survive despite the wide area of infarction due to LMT lesion. Coronary angiograms performed 37 days after the CABG showed that the graft to LAD was completely occluded and the LCX graft was patent with partial stenosis. Treadmill test at this time induced an anginal episode with ischemic ECG changes on moderate exercise, indicating the presence of significant area of ischemic myocardium. For salvage of the ischemic myocardium, percutaneous transluminal coronary angioplasty (PTCA) was successfully performed for the LMT stenosis, resulting in no episode of angina nor ischemic ECG changes during exercise loading.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A case of myocardial infarction due to the left main trunk lesion, in which percutaneous coronary recanalization and emergency coronary-aorto bypass graft, and subsequent percutaneous coronary angioplasty were effective not only from a viewpoint of survival but from comeback to social life]. 260 80

Two recipients of orthotopic liver transplants (OLT) underwent intra-arterial thrombolytic treatment for hepatic artery thrombosis. Complete clot lysis was achieved in both using infusion of high-dose urokinase directly into the thrombus for 12 and 3 hours, respectively. Percutaneous transluminal angioplasty (PTA) was later carried out successfully on various strictures. Doppler ultrasonography confirmed arterial permeability one month after treatment. Liver transplantation is now an accepted therapeutic option in some patients with irreversible liver failure. Although the results of this procedure have improved radically since cyclosporine was introduced in 1978, life-threatening postoperative complications still occur. The one with the worst prognosis is hepatic artery thrombosis (HAT), with 64% mortality despite retransplantation. HAT was found in 7.4% of liver transplant recipients in a recent review of the most important group of these patients. Fibrinolytic treatment using an exogenous plasminogen activator, urokinase (UK), is effective and safe in the thrombotic obstruction of acute pulmonary embolism, acute myocardial infarction, and graft or peripheral arterial occlusion. We used intra-arterial thrombolysis in two patients with HAT of the liver graft, to avoid retransplantation and to treat a complication secondary to percutaneous transluminal angioplasty (PTA) of an anastomotic stricture, respectively. To our knowledge, this is the first report of treatment of HAT by direct infusion of urokinase in liver transplantation.
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PMID:High-dose intra-arterial urokinase for the treatment of hepatic artery thrombosis in liver transplantation. 261 76


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