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)

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.
Cathet Cardiovasc Diagn 1990 Feb
PMID:Management of complicated coronary angioplasty by intracoronary urokinase and immediate re-angioplasty. 210 94

Many studies are currently evaluating the potential role of thrombolytic therapy in patients with ischemic syndromes who have undergone previous coronary artery bypass grafting. Limited experience has been published regarding the use of local urokinase and streptokinase infusions and the use of systemic recombinant tissue-type plasminogen activator as thrombolytic agents in patients with previous coronary artery bypass surgery. To date, however, there has been no published experience regarding the use of recombinant tissue-type plasminogen activator (rt-PA) either systemically or locally in the post-bypass patient where angiographic demonstration of aortocoronary saphenous vein graft obstruction was available pre- and post-therapy. Similarly there has been no previous report of the use of rt-PA infused locally to recanalize an occluded aortocoronary saphenous vein graft. This report describes successful thrombolysis and subsequent balloon angioplasty of saphenous vein grafts with angiographically documented thrombus using systemic and local rt-PA infusion.
Cathet Cardiovasc Diagn 1990 Mar
PMID:Systemic and local saphenous vein graft thrombolysis using a tissue plasminogen activator. 210 79

We describe the percutaneous management of emboli that occurred in 3 patients during hot tip laser-assisted angioplasty procedures. One embolus was lysed with direct, local infusion of urokinase using an open-ended guidewire. Another embolus was removed using the transcatheter aspiration technique. The third embolus was partially lysed and then, using a steerable guidewire, displaced placed into a distal side branch. In all 3 cases of embolization, distal blood flow was reestablished using percutaneous techniques, obviating the need for surgical intervention.
Cardiovasc Intervent Radiol
PMID:Percutaneous management of emboli associated with hot tip laser-assisted angioplasty. 214 94

We report on the complication rates in 660 consecutive coronary angioplasties (725 lesions) performed using four procedures that differed with respect to catheter technology and adjuvant medication. After the PTCA regimen in our laboratory had been changed from conventional steerable systems to the monorail technique, we observed a significant increase in the incidence of transient vessel occlusions from 2.6% to 7.7%, of permanent occlusions from 3.6% to 8.8%, and of intracoronary thrombus-formation from 2.6% to 5.5%. This was associated with the frequent observation of thrombotic material on the partially Teflon-coated guidewires. Coronary perfusion with urokinase (1,670-6,670 U/min) lead to a further increase in the complication rates (10.4%/10.3%/6.5%). Our present percutaneous transluminal coronary angioplasty (PTCA)-regimen (monorail technique with P.E.T. balloons, fully silicon-coated guidewires, no urokinase) shows an incidence of 3.8% for intermittent and recurrent coronary occlusions and 1.9% for permanent occlusions. Urokinase did not prevent intracoronary thrombus formation with the monorail technique. Furthermore, we suspect that in the case of PTCA-induced regional intimal dissection, fibrinolysis can prevent reestablishment of intima adherence to the vessel wall. Because five procedural deaths were observed in the 212 patients treated with i.c. urokinase as opposed to three deaths in the 448 procedures without urokinase, we feel that i.c. urokinase in PTCA is a potentially harmful regimen. We suggest that the monorail technique should be performed with fully silicon-coated guidewires and without urokinase.
Cathet Cardiovasc Diagn 1990 Oct
PMID:Influence of catheter technology and adjuvant medication on acute complications in percutaneous coronary angioplasty. 222 38

We report the case of a 74-year-old woman with multi-level arterial occlusive disease and severe ischemia of the right lower extremity who underwent a re-operative femoro-femoral and a right femoro-popliteal bypass graft. Her right foot remained non-viable post-operatively despite patent grafts. She then underwent a 12-hour infusion of urokinase through a percutaneously placed popliteal artery catheter during that first post-operative day, with salvage of the right leg.
J Cardiovasc Surg (Torino)
PMID:Immediate post-operative urokinase infusion: extending the limits of limb salvage surgery. 234 76

The dose-response of an intravenous i.v. infusion for 30 min of recombinant human single-chain urokinase-type plasminogen activator (rscu-PA) was investigated in dogs with 1-h-old clots in the left anterior descending coronary artery. The clots were induced with a copper coil, and thrombolysis was monitored by repeated coronary angiography. Intravenous infusion of rscu-PA at a rate of 2 micrograms/kg/min did not induce lysis within 30 min (n = 4). Infusion at a rate of 4 micrograms/kg/min in 7 dogs produced complete lysis in 2 (within 25 and 27 min), partial lysis in 2 (within 18 and 25 min), and no lysis in 3. Infusion at 8 micrograms/kg/min in four dogs caused complete lysis in three dogs within 18 +/- 3 min (mean +/- SD) and partial lysis in the fourth animal. Infusion at 20 micrograms/kg/min in four dogs induced complete lysis within 14 +/- 3 min. A linear correlation was observed between the infusion rate and the plateau level of rscu-PA in blood. At the highest infusion rate (20 micrograms/kg/min), the concentration of rscu-PA in blood was 2.5 +/- 0.45 microgram/ml, but this was not associated with systemic fibrinolytic activation because the alpha 2-antiplasmin and fibrinogen levels remained essentially unchanged. It is concluded that i.v. infusion of recombinant single-chain urokinase-type plasminogen activator (rscu-PA) at a sufficiently high rate (greater than or equal to 8 micrograms/kg/min) produces coronary thrombolysis without systemic fibrinolysis in dogs.
J Cardiovasc Pharmacol 1987 Jan
PMID:Thrombolysis with recombinant human single-chain urokinase-type plasminogen activator (rscu-PA): dose-response in dogs with coronary artery thrombosis. 243 1

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)
Thorac Cardiovasc Surg 1987 Dec
PMID:The therapy of acute myocardial infarction: current state of the art. 244 99

Currently, the effects of the thrombolytic drugs are tested in vivo in dog or rabbit models that require a relatively large amount of the drug. The goal of the present study was to describe a new model that would allow one to test the in vivo thrombolytic effect of drugs with a limited amount of compound. For this purpose, we have induced a pulmonary embolus in anesthetized rats by injecting I125 radiolabeled clots into the venous circulation and we have measured the lysis of these clots occurring either spontaneously or induced by increasing doses of wild-type tissue plasminogen activator (tPA) (from 0.125 to 2 mg/kg i.v.) or by streptokinase (750,000 I.U./kg i.v.) or urokinase (750,000 I.U./kg i.v.). In the plasma of these rats, we have also measured the plasminogen activation activity of tPA as well as the concentrations of plasminogen, fibrinogen, and alpha 2-antiplasmin. Spontaneously, there was a time dependent thrombolysis (33%/h) that could be partially inhibited by aprotinin. Wild-type tPA induced a dose-related thrombolysis with a limited decrease of plasma fibrinogen concentration with doses over 0.25 mg/kg. Streptokinase and to a smaller extent urokinase induced a larger hemostatic breakdown (as indicated by systemic fibrinogenolysis, plasminogen activation, and alpha 2-antiplasmin consumption). We conclude that the rat pulmonary embolus model is suitable for testing the thrombolytic efficacy, potency, and the fibrin specificity of thrombolytic drugs and requires a smaller amount of drug than the previously described in vivo models.
J Cardiovasc Pharmacol 1988
PMID:Experimental pulmonary embolus in the rat: a new in vivo model to test thrombolytic drugs. 246 50

The application of thrombolytic agents in acute myocardial infarction has shown to be an effective form of therapy in terms of reperfusion and improvement of myocardial function based on the reduction of infarct size, and decrease of mortality. From the presently available intravenous agents, urokinase and rT-PA have opening rates of 65 and 60%, respectively. The reperfusion rate as well as the improvement of myocardial infarction are time dependent, resulting in the necessity of reopening the occluded coronary artery within 2.5 h. From the available knowledge, time is not only the most important, but the medically most variable parameter. Thus, the need of early diagnosis and rapid installation of reperfusion result in the necessity of a broader instruction of the public and the treating physicians. Presently ongoing studies will show whether beginning therapy at home or in the ambulance may improve our already extremely promising results achieved today. They will, however, supposedly describe subgroups, i.e., of small inferior infarctions, in which conventional therapy has to be preferred instead of the more aggressive, subtle thrombolysis, PTCA, and cardiac surgery.
J Cardiovasc Pharmacol 1988
PMID:Beta-blockade in myocardial ischemia: acute interventions in myocardial infarction. 246 36

The current revolution in the treatment of acute myocardial infarction by means of thrombolytic therapy has as its underlying strategy three aims: early restoration of the blood flow in order to salvage jeopardized but still viable tissues; limitation of acute consequences of ischemic heart disease, such as infarct size, ventricular fibrillation, and pericardial effusion; and preservation, as far as possible, of ventricular function. It is also hoped that these three achievements will result in reduced short- as well as long-term mortality rates. The techniques employed in this overall strategy are still under investigation, and several leading pharmacological compounds vie for supremacy: streptokinase (SK) and its anisoylated form (APSAC), recombinant technique tissue type plasminogen activator (rt-PA), and urokinase (UK) with or without prourokinase (PUK). Other pharmacological agents, such as angiotensin converting enzyme (ACE) inhibitors, beta-blockers, Ca2+ antagonists, and O2 radical scavengers, might find here their "finest hour" yet. In addition, the underlying anatomy may require early or, where needed, delayed PTCA, backed up by coronary artery bypass grafting. Thus, the tactics of the intervention may vary from case to case and indeed from center to center depending on experience and facilities, but the strategic conclusion is clearly the same: early reperfusion is a must if one wishes to save ischemic but still viable tissue.
J Cardiovasc Pharmacol 1989
PMID:Acute consequences of ischemic myocardial damage. 248 24


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