Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

The pivotal role of thrombosis in unstable angina and non-Q-wave myocardial infarction has been established recently. To assess the value and safety of thrombolytic therapy compared to conventional antithrombotic therapy (aspirin) in arresting progression in this setting to recurrent ischemic end-points, 25 patients presenting with unstable angina and an electrocardiogram showing subendocardial ischemia were randomized to receive either aspirin 325 mg daily, or urokinase 3 x 10(6) U intravenously, over 30 minutes followed by heparin. Incidence of endpoints (intractable ischemia requiring mechanical intervention, new myocardial infarction or death) was determined over 7 days. Coronary arteriography was performed at 24 to 72 hours to determine extent of coronary artery disease and morphologic severity of the culprit lesion, graded by a semiquantitative scoring system ranging from 4+ (definite thrombosis) to 0 (chronic lesion). In the first 24 hours, 7 of 13 aspirin versus 1 of 12 urokinase patients exhibited ischemia progression (p less than 0.05). By 7 days, progression to a primary ischemic endpoint occurred in 8 of 13 aspirin patients (3 myocardial infarctions and 5 intractable ischemias) versus 3 of 12 urokinase patients (2 intractable ischemias and 1 death) (p = 0.18). The apparent benefit of urokinase followed by heparin compared to conventional aspirin therapy in arresting early progression of unstable angina or non-Q-wave myocardial infarction was not associated with enhanced culprit lesion morphology (mean lesion severity score 2.7 +/- 1.5 vs 2.8 +/- 1.6 in aspirin-treated patients). Large scale, randomized trials to assess the clinical utility of urokinase for unstable angina are warranted.
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PMID:Urokinase plus heparin versus aspirin in unstable angina and non-Q-wave myocardial infarction. 280 50

During the period 1985 to 1988, salvage of free tissue transfers with streptokinase and urokinase was performed in six patients with 83.3 percent success. The no-reflow phenomenon, manifested by poor intraflap flow in spite of a patient arterial anastomosis, was present in four successful patients. Streptokinase was used in four patients with 100 percent success with a dose range of 50,000 to 125,000 U. Urokinase was used in two patients with 50 percent success with a dose range of 50,000 to 100,000 U. Successful cases were reexplored within 6 hr of indication of ischemia. The unsuccessful case was reexplored 9 hr after ischemia as indicated by a laser Doppler flowmeter. Subflap hematoma occurred in one patient. A technique is described that selectively perfuses the free flap with the thrombolytic agent and prevents systemic complications.
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PMID:Salvage of free tissue transfers using thrombolytic agents. 281 Feb 4

Intraoperative intraarterial fibrinolytic therapy (IIFT) was employed in 28 patients with acute limb ischemia. In 17 patients, significant residual calf thrombus was demonstrated by completion arteriography after standard balloon catheter thromboembolectomy, whereas in 11, pretreatment arteriography was not obtained. With the patient systemically heparinized, a bolus of fibrinolytic agent was instilled into the distal vessels below an inflow occlusion clamp. Among the 17 patients under angiographic control, arteriography was repeated after 30 minutes and a second bolus was injected if significant residual thrombus was still present. Successful lysis was achieved in 88% of these 17 limbs and streptokinase (SK) and urokinase (UK) were equally effective. The dosage of SK varied between 50,000 and 150,000 units (seven patients) and of UK between 35,000 and 150,000 units (21 patients). Serum fibrinogen levels declined significantly after IIFT (t test; p less than 0.05), but the average level remained within the normal range. Major bleeding developed in two patients, both of whom received SK and underwent a concomitant major abdominal vascular procedure, with a severe fall in fibrinogen values to 10 and 17 mg/dl. A minor groin hematoma occurred in one patient treated with UK. There was a significant difference in the incidence of bleeding between SK (2/7) and UK (1/21) (chi 2; p less than 0.05). Compartment syndrome developed in six limbs (21%). Amputation was required in two patients (7%). There was no correlation between prolongation of ischemia time as a result of IIFT and the incidence of compartment syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fibrinolytic treatment of residual thrombus after catheter embolectomy for severe lower limb ischemia. 291 Nov 35

Administration of intraarterial fibrinolytic agents has been recommended after balloon catheter thrombectomy to reduce retained thrombus and to improve the patency of collateral vasculature. However, the potential for improvement in the viability of skeletal muscle after ischemia as a result of this therapy has not been evaluated. We investigated the effect of intraarterial urokinase (UK) on the salvage of ischemic skeletal muscle in a bilateral, in vivo, isolated gracilis muscle model. In six anesthetized dogs each gracilis muscle was subjected to 5 hours of ischemia by temporary occlusion of the gracilis artery. Before reperfusion, the experimental muscle received an intraarterial infusion of UK (30,000 units) whereas the control muscle received saline solution. Each muscle was then reperfused for 90 minutes. Triphenyltetrazolium chloride staining demonstrated infarction of 20.2% +/- 8.1% in control muscles compared with 8.6% +/- 6.2% in UK-infused muscles (p less than 0.01). Control muscles gained significantly more weight from edema (33.6 +/- 5.9 gm) than UK-infused muscles (18.2 +/- 4.1 gm; p less than 0.05). Coagulation studies confirmed that an isolated fibrinolytic effect occurred on the experimental side. These studies suggest that intraarterial UK may be a useful adjunctive therapy after revascularization of the acutely ischemic limb and that further clinical trials are recommended.
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PMID:Intraarterial urokinase increases skeletal muscle viability after acute ischemia. 291 Nov 36

Percutaneous aspiration thromboembolectomy (PAT) is an angiographic technique that can be used to remove thromboembolic debris from the distal lower extremity circulation. This procedure employs a specially designed catheter-sheath system, which can be used alone or in combination with balloon angioplasty or thrombolytic drugs (streptokinase 10,000 U/hr or urokinase 100,000 U/hr for 6 hours) to remove thromboembolic material. PAT is best suited for treating iatrogenic emboli resulting from intra-arterial catheterization or balloon angioplasty but can be used as a supplement to Fogarty embolectomy when retained distal clot cannot be retrieved by surgical means and for removal of primary distal emboli of peripheral vascular or cardiac origin. PAT was used in 42 patients with acute threatening limb ischemia. Successful clot retrieval and limb salvage were achieved in 40 of the 42 patients (95%). The major complication was groin hematoma (7 of 42 patients, 17%) and one death occurred as a result of myocardial infarction (2.4%). PAT enhances the therapeutic role of angiography and can be used as an alternative to surgical embolectomy in selected patients.
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PMID:Percutaneous aspiration thromboembolectomy (PAT): an alternative to surgical balloon techniques for clot retrieval. 293 4

Early reperfusion of occluded coronary arteries offers great promise as a method for minimizing myocardial damage after acute myocardial infarction. Such reperfusion is usually attempted via administration of fibrinolytic agents. Urokinase may hold marginal advantages over streptokinase, especially in patients with high preexisting titers of antistreptokinase antibodies. These minor differences, however, pale in comparison to important advantages demonstrated by the newly developed agent, tissue plasminogen activator (t-PA). The advantages of t-PA derive primarily from its property of binding to, and being activated by, fibrin. Consequently the generated plasmin is also fibrin-bound, the bound plasmin is protected from circulating antiplasmin and therefore more efficiently utilized, and circulating fibrinogen is spared. Preliminary clinical experience indicates that the frequency of favorable response after intravenous administration of t-PA is considerably greater than after SK. A major determinant of clinical benefit after reperfusion is the brevity of ischemia. Selective intracoronary infusion of fibrinolytic agent produces faster lysis than does intravenous infusion, and rate of lysis may be further accelerated by transcatheter disruption of clot and intrathrombic injections of highly concentrated urokinase or t-PA. Even maximally accelerated lysis, however, cannot fully compensate for the inherent delay imposed by catheterization. For that reason, prompt intravenous infusion of fibrinolytic agents, presumably t-PA, seems preferable to the intracoronary route. In the effort to initiate fibrinolytic therapy at the earliest feasible time after infarction, administration by paramedics, or even home administration after training, is a program worthy of exploration.
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PMID:Streptokinase, urokinase, and tissue plasminogen activator: pharmacokinetics, relative advantages, and methods for maximizing rates and consistency of lysis. 310 38

The use of fibrinolytic agents to control the fibrinolytic enzyme system and lyse pathologic fibrin deposits or thrombus has now assumed a position with anticoagulants and vascular surgery in the physician's therapeutic armamentarium. The principal exogenous activators that are used clinically are streptokinase, urokinase, and tissue plasminogen activator. Acute arterial occlusions are more likely than chronic occlusions to respond to thrombolytic therapy, especially if treatment is instituted within a few hours of onset of symptoms and if the disease is due to embolic material rather than in situ thrombosis. Since the duration of drug infusion necessary to lyse arterial thrombus cannot be predicted, patients in whom tissue viability cannot be determined or in whom ischemia cannot be tolerated during the drug infusion interval are not candidates for intraarterial fibrinolytic drug infusion. In treating patients with venous occlusion, thrombolytic therapy is more effective against proximal clots than in calf thrombosis. No protective effect from pulmonary embolism has been noted in trials comparing heparin with streptokinase. Fifty percent of patients with an initial episode of deep venous thrombosis treated within 72 hours of onset will have complete resolution of thrombus with preservation of valve function.
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PMID:Application of thrombolytic therapy in vascular occlusive disease. A surgical view. 311 28

Significant current interest has focused on the possible value of fibrin-selective thrombolytic agents in acute stroke. Acute thrombosis contributes to carotid and vertebrobasilar arterial occlusions in the majority of acute stroke patients. Hence, fibrin(ogen)olytic agents may produce arterial recanalization and clinical benefit in thrombotic stroke. There are, however, unique features of cerebral tissue that suggest caution with the use of fibrin-selective agents in cerebral ischemia. The specific vascular anatomy and collateral flow suggest that salvage of the "ischemic penumbra" following vascular recanalization in focal ischemia is more likely to be successful than attempts in global ischemia. Recanalization may be associated with reperfusion injury and, more importantly, the risk of hemorrhagic transformation. There is little concrete information regarding the relative contribution of either event to post-thrombolysis cerebral injury. Early studies with exogenous fibrinolytic agents (urokinase, streptokinase) in completed stroke were regarded as inconclusive, demonstrating only an increased risk of intracerebral hemorrhage. Subsequent pilot studies in carotid and in vertebrobasilar territory thrombotic stroke have demonstrated that recanalization can result when exogenous agents are infused just proximal to the cerebral artery occlusion by interventional neuroradiological techniques. This experience and the advent of fibrin-selective agents (tissue plasminogen activator [tPA] and single-chain urokinase plasminogen activator) have led to the development of a multicenter prospective safety/dose-ranging study of tPA in acute (less than eight hours from symptom onset) thrombotic stroke. Following initial clinical assessment, computed tomography scan, and angiography, each patient with a documented cerebral artery occlusion appropriate to the clinical syndrome receives a preassigned intravenous dose of tPA over 60 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Investigational use of tPA in acute stroke. 314 17

After describing the mechanism of action, results and local and general complications of classical thrombolytic agents (streptokinase and urokinase) administered systemically, locally and peroperatively, then of modern thrombolytic agents (acyl enzyme, tPA and scuPA), the future perspectives of arterial fibrinolysis are discussed. These are based upon: analysis of the comparative efficacy of the different thrombolytic agents in the light of results seen, not only in peripheral arterial pathology but also in other indications, as in coronary pathology; discussion of the methods of administration of the thrombolytic agent in such a way as to obtain an optimal local concentration and at the same time reduced systemic fibrinolysis. better definition of the indications of thrombolysis in acute ischemia of the limbs in comparison with other therapeutic approaches, in particular surgery, taking into account the degree of ischemia, of etiological mechanism and the site of the arterial obstruction.
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PMID:[Arterial thrombolysis. Review and future prospects]. 314 94

In this retrospective analysis we report our treatment experience in 65 consecutive patients with clinical signs of severe brainstem ischemia with angiographically demonstrated thrombotic vertebrobasilar artery occlusions who received either local intra-arterial thrombolytic therapy (urokinase or streptokinase) (43 patients) or conventional therapy (antiplatelet agents or anticoagulants) (22 patients). We analyzed the data with respect to cerebral artery occlusion patterns, posttreatment arterial recanalization, and the clinical categories of favorable/unfavorable outcome and survival/death. In subgroup analyses, recanalization in patients who received thrombolytic therapy correlated significantly with clinical outcome; in 19 of 43 patients, recanalization was demonstrated angiographically, while in 24 patients the occlusion persisted. All patients without recanalization died, but 14 of the 19 patients displaying recanalization survived (p = 0.000007), 10 with a favorable clinical outcome. Only three of the 22 patients who received conventional therapy survived, all with a moderate clinical deficit. When we compared the treatment groups, highly significant differences in both outcome quality (p = 0.017) and survival (p = 0.0005) were found to depend on establishing recanalization. Our data support the concept that technically successful thrombolysis of vertebrobasilar artery occlusions is associated with beneficial clinical outcome.
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PMID:Intra-arterial thrombolytic therapy improves outcome in patients with acute vertebrobasilar occlusive disease. 317 80


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