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

Pulmonary thromboembolism is a widespread problem and is an important cause of death in patients with a variety of medical and surgical conditions. There have been few significant advances in the understanding of the aetiology beyond additional evidence confirming the importance of Virchow's triad. An impressive list of epidemiological associations has been compiled, however. Some knowledge of the natural progression of the disease is required as an aid in the understanding of the application of the therapeutic and prophylactic measures available in the management of pulmonary embolism. It would seem that at least two-thirds of pulmonary emboli are non-fatal, and in these cases the natural resolution, even of comparatively large embolic masses, is very efficient in patients without pre-existing cardiopulmonary disease. Diagnosis may prove difficult and most ancillary investigations are of questionable value. On the other hand, pulmonary radio-isotope scanning is far more specific and pulmonary angiography is a comparatively simple and complication-free diagnostic procedure. Prophylaxis is a real and practical aim, especially following surgery or myocardial infarction. In these groups widespread clinical trials of prophylactic measures have been made possible by the objective radio-iosotope screening techniques. Mechanical means of preventing venous stasis and anticoagulation appear effective. In addition, low-dose subcutaneous heparin seems to be as useful as heparin in conventional dosage. Apart from conventional supportive therapy, there are three major approaches to the treatment of pulmonary embolism. Heparin remains the mainstay, particularly in the less severe cases, hopefully preventing propogation of thrombosis and recurrence of embolism, thus allowing resolution to take place. Thrombolytic therapy with streptokinase or urokinase is capable of producing far more rapid dissolution of pulmonary emboli with consequent theoretical advantages over heparin. No reduction in mortality has been shown using thrombolytic therapy. Patients who fail to respond satisfactorily to acute resuscitative measures may require pulmonary embolectomy.
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PMID:Pulmonary embolism: current therapeutic concepts. 77 78

Six cases of post-embolic chronic cor pulmonale are presented. All six were treated with thrombolytic agents (4 with streptokinase, 2 with urokinase), and in only one case was improvement maintained at the end of one year. Two patients underwent a disobliterative procedure of the pulmonary artery, together with ligation of the inferior vena cava. One of these operations was unsuccessful, and the other had a successful outcome, as confirmed by objective assessment with angiography, scintigraphy and haemodynamic studies. The literature is reviewed at this stage. It was found that the fibrinolytic agents had some chance of working only if the condition was less than a few months old. One major drawback to surgical disobliteration that cannot be foreseen before operation is the presence of thromboses at the arteriolar level in subjects whose main arteries are already blocked proximally. Nervertheless it is possible to obtain good results by surgery, and the operation is worth attempting in young subjects, given the poor prognosis of the untreated condition.
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PMID:[Chronic pulmonary artery thrombosis. Therapeutic modality. Apropos of 6 cases]. 81 83

Sixteen patients who had massive pulmonary thromboembolism and shock had no history of cardiopulmonary disease. We present an evaluation of the short-term effects of fibrinolytic treatment consisting of intrapulmonary administration of a bolus of 500,000 IU of urokinase followed by infusion of 1 x 10(6) IU into the right auricle over 12 h and subsequent intravenous infusion of heparin. For each patient, the effectiveness of treatment was evaluated by comparing pretreatment angiographic and hemodynamic parameters with those measured 48 h after the start of treatment. The Miller index fell from 22.9 +/- 5.9 to 9.8 +/- 3.3 (p less than 0.001), with a mean improvement of 57.2 percent. All the hemodynamic parameters studied (cardiac output and index, total pulmonary vascular resistance, and systolic, diastolic, and mean pulmonary vascular pressure) also exhibited statistically significant differences between pretreatment and posttreatment values (p less than 0.001 for each parameter), with a mean improvement of over 30 percent in each case. All the patients survived, and in no case did treatment fail; only one patient (6.2 percent) suffered severe hemorrhage. We conclude that this form of administration of urokinase is useful for patients with critical massive pulmonary thromboembolism.
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PMID:Treatment of massive pulmonary thromboembolism with low intrapulmonary dosages of urokinase. Short-term angiographic and hemodynamic evolution. 164 11

Life-threatening chronic cor pulmonale occurred in a 22-year-old woman with congenital 3 degrees atrioventricular block, 6 years after implantation of a pacemaker and 3 1/2 years after removal of the pacemaker (the electrodes were too firmly attached to be removed). The emboli originated from the right-atrial thrombi which had formed around the electrodes left in situ. The embolic source shrank during systemic administration of urokinase, initially 600,000 IU in 60 min, then 100,000 IU per hour, and pulmonary perfusion improved transiently. Nonetheless the patient became breathless on the slightest physical exertion. Recurrent syncopal attacks with marked increase of pulmonary artery pressure necessitated pulmonary thrombendarterectomy and removal of the electrode and wires. Thereupon the patient's condition clearly improved so that 6 months postoperatively her exercise tolerance was again unimpaired.
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PMID:[Chronic thromboembolic cor pulmonale in pacemaker-associated right atrial thrombi. Pulmonary thromboendarterectomy with removal of the electrodes as a life-saving measure]. 199 96

To evaluate hemodynamic, angiographic, and biological effects of a single bolus of urokinase, an open descriptive trial was conducted in a homogeneous group of 14 patients with acute life-threatening pulmonary emboli and without prior cardiopulmonary disease. For every patient the efficacy of the treatment was evaluated by comparing control and posttherapeutic values after the bolus injection of 15,000 IU/kg body weight urokinase (urinary source) administered in 10 min in the right atrium, followed by continuous intravenous full-dose heparin therapy. In two patients clinical status, hemodynamics, vascular obstruction, and biological (fibrinogen and plasminogen levels) parameters remained unchanged. One of these two patients died, making the mortality rate for the whole group 7%. Twelve of 14 patients showed rapid clinical improvement. Evaluation at 12 hr demonstrated significant decreases in pulmonary vascular obstruction (Miller index, 34%), total pulmonary vascular resistances (37%), and fibrinogen and plasminogen levels (41% and 40%, respectively), without any significant change in cardiac index. The hemodynamic sequential measurements performed (1,3, 6, and 12 hr) in seven of the 12 improved patients showed that the greatest percentage of the total hemodynamic improvement occurred within the first 3 hr after bolus administration of urokinase. No severe hemorrhagic complications were observed. Because of its rapid efficacy and its low cost, the bolus technique appeared particularly useful in the treatment of patients with acute life-threatening pulmonary emboli.
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PMID:Effects of a single bolus of urokinase in patients with life-threatening pulmonary emboli: a descriptive trial. 648 99

We report the case of a woman treated with urokinase for acute pulmonary embolism with a right-sided heart thrombus. She developed life-threatening acute cor pulmonale which dramatically improved within 4 h with recombinant tissue plasminogen activator (rtPA). We emphasize the clinical interest of rtPA for the treatment of life-threatening pulmonary embolism.
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PMID:Life-threatening pulmonary embolism with right-sided heart thrombus. Rapid recovery with recombinant tissue plasminogen activator. 816 78

Identification of a novel therapy for prevention of sudden death by ischemic cardiac infarction is an area of intensive investigation. We here report that the mortality due to an experimental acute myocardial infarction (AMI) was markedly increased in mice deficient in alpha2-antiplasmin (alpha2-AP(-/-) mice) but not in mice deficient in other components acting in fibrinolysis (tissue-type PA, urokinase type PA, or plasminogen activator inhibitor-1) even if the infarct area in alpha2-AP(-/-) mice was not different from those in the other mice. Echocardiography showed in alpha2-AP(-/-) mice after AMI an overload of the right ventricle and that pulmonary permeability was increased. According to the experiments using explanted myocytes and vascular smooth muscle cells, it was found that the amount of secreted vascular endothelial cell growth factor (VEGF) in alpha2-AP(-/-) mice was markedly increased compared with that in wild-type mice. Finally, an injection of an anti-VEGF antibody decreased the mortality after AMI in alpha2-AP(-/-) mice. Plasmin cleaves extracellular matrix-bound VEGF to release a diffusible proteolytic fragment and is inactivated mainly by alpha2-AP. Therefore, lack of alpha2-AP could markedly result in overrelease of VEGF by the continuous activation of plasmin because of AMI and could result in an acute cor pulmonale. Our results provide new aspects on the role of alpha2-AP and VEGF in the pathogenesis of cardiac events.
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PMID:Lack of alpha2-antiplasmin promotes pulmonary heart failure via overrelease of VEGF after acute myocardial infarction. 1223 60

Various studies demonstrated an interdependence between rheological parameters and advanced stages not only of ischaemic heart disease and peripheral arterial occlusive disease, but also of chronic obstructive lung disease. In ischaemic heart disease, rheological alterations in the poststenotic circulation can result in impairment of the oxygen supply of the myocardium. Rheological therapies aim for a reduction in plasma viscosity and improved microcirculatory flow by means of a reduction of the elevated levels of fibrinogen. As an example, intermittent therapy with urokinase has been established as a treatment of refractory angina pectoris. Treatment with fibrates also can result in an improvement of microcirculation due to reduced hepatic fibrinogen synthesis. Treatment with statins leads to an improvement of microcirculation due to effects on serum lipids. In patients with chronic obstructive lung disease and cor pulmonale who, secondary to chronic hypoxia, develop polycythaemia and disturbances in pulmonary microcirculation, isovolumic haemodilution may result in a reduction of pulmonary arterial pressure with consecutively increased cardiac output and improved exercise capacity.
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PMID:[Rheological determinants of end-organ damage]. 1463 81