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 incidence of deep venous thrombosis or pulmonary embolism after lung or heart-lung transplantation has not been well defined. Pulmonary embolism may be of particular concern in the postoperative period owing to an inadequately developed or absent collateral bronchial circulation and potential risk of pulmonary infarction. Fourteen (12.1%) of 116 patients undergoing either lung (n = 87) or heart-lung (n = 29) transplantation developed thromboembolic complications 10 days to 36 months after operation. Deep vein thrombosis developed in nine patients, including three with upper body thrombosis related to indwelling central venous catheters. Seven patients (6%) had pulmonary embolism, and three of them died. Resolution of pulmonary embolism was successfully accomplished by selective pulmonary artery infusion of urokinase in three patients without complications. Our experience indicates that deep vein thrombosis and pulmonary embolism are significant problems after lung transplantation. Mortality is high in those patients in whom pulmonary embolism develops. Therefore, a comprehensive prevention protocol is warranted.
J Thorac Cardiovasc Surg 1995 Aug
PMID:Deep venous thrombosis and pulmonary embolism after lung transplantation. 763 73

The authors' experience with 46 patients treated over 8.5 years was reviewed to determine the optimal secondary revascularization procedure after occlusion of a unilateral aortobifemoral graft limb. A total of 64 procedures was performed on these patients to restore and maintain graft patency. Repetitive operations for reocclusion were needed in 14 patients (30%). Transcatheter thrombolytic therapy was used in 14 patients, four as sole therapy and 10 in conjunction with operation. The mean time from aortofemoral grafting to presentation with graft limb occlusion was 59.4 months. Rest pain or severe ischemia was present in 85%, and severe claudication in the remainder. Some 78% had urgent operation after diagnostic angiography and catheter-directed thrombolytic therapy was attempted in 22%. The etiology of graft thrombosis was outflow obstruction in 78.2% of cases. Inflow was obtained by surgical thrombectomy in 35 and by lytic therapy in 13. Extra-anatomic inflow was used in 11 and intra-abdominal thrombectomy or redo aortofemoral grafting in five. Outflow procedures, mainly profundaplasty, were performed in all but five cases (four urokinase and one surgical). Infrainguinal bypass was needed in 10 cases in addition to the groin reconstruction. Catheter-directed thrombolysis was successful in 13 of 14 instances; however, in nine of these residual stenosis was disclosed in the outflow requiring surgical repair. Ultimately, 12 of 14 cases treated with thrombolysis required surgical intervention. Cumulative patency for all procedures was 68%. Complications were seen in 14% of cases. Operative mortality was 5%, and limb salvage was obtained in 85%.(ABSTRACT TRUNCATED AT 250 WORDS)
Cardiovasc Surg 1995 Jun
PMID:Aortofemoral graft occlusion: strategy and timing of reoperation. 765 41

The outcome of 72 direct intra-arterial urokinase infusions was studied prospectively. Thirty four were performed for native arterial occlusion and 38 for bypass graft occlusion; the immediate success rates were 67.5 and 84% respectively. The overall incidence of complications was 26%. Median follow-up was 36 (range 1-60) months. Seventeen patients (27%) died during follow-up; nine (14%) required a major amputation. Among patients with native arterial occlusion, 29% had no adjunctive procedure after thrombolysis; of these patients, 85% remained patent at a median of 21 (range 3-42) months. Among bypass occluded patients, only two (6%) had no lesion revealed after successful lysis; both bypasses remain patent at 54 and 58 months respectively. For patients treated with balloon angioplasty immediately after successful thrombolysis, 62% with native arterial occlusion remained patent at a median of 39 (range 2-60) months, whereas only 27% of bypass occlusion patients were patent at a median of 11 (range 2-40) months. Of patients requiring a surgical procedure after thrombolysis, 23 new bypasses (15 vein, eight prosthetic) were placed (nine in native arterial occlusion patients, 14 in bypass occlusion patients). In addition, there were 15 other surgical procedures, including six thrombectomies, four vein patch angioplasties, four vein jump grafts and one endarterectomy. The primary and secondary patencies for the 15 new vein bypasses placed were 81 and 88% respectively at a median follow-up of 36 months. Good immediate results were experienced with urokinase thrombolysis for peripheral arterial and graft occlusions. However, multiple adjunctive procedures were required to maintain patency.(ABSTRACT TRUNCATED AT 250 WORDS)
Cardiovasc Surg 1995 Jun
PMID:Late results of a prospective study of direct intra-arterial urokinase infusion for peripheral arterial and bypass graft occlusions. 765 44

We used a canine model of embolic pulmonary hypertension induced by intravenous (i.v.) injection of autologous thrombi to evaluate whether the novel recombinant plasminogen activator (r-PA) BM 06.022 reversed pulmonary hypertension. The effects of BM 06.022 after bolus injection were compared with those of vehicle, alteplase, urokinase, and anistreplase in 6 dogs per group. Thirty minutes after initiation of treatment, the decrease in pulmonary artery pressure (PAP) caused by a bolus of 200 kU/kg (0.35 mg/kg) BM 06.022 was greater (p < 0.05) than that caused by a 2-h infusion of 1.33 mg/kg alteplase or of 40,000 U/kg urokinase and that caused by a bolus of 0.4 U/kg anistreplase but not that caused by a 15-min infusion of 1 mg/kg alteplase. At 3 h, all thrombolytic agents had reduced PAP equally. The greatest measured plasma concentration of BM 06.022 was higher (p < 0.05) than that of 2-h infused alteplase (4,498 +/- 716 vs. 519 +/- 119 IU/ml). We conclude that because of its bolus-pharmacokinetics, BM 06.022 more rapidly reversed thromboembolic pulmonary hypertension than did 2-h infusion of alteplase or urokinase or a bolus of anistreplase.
J Cardiovasc Pharmacol 1993 Mar
PMID:Rapid reversal of canine thromboembolic pulmonary hypertension by bolus injection of the novel recombinant plasminogen activator BM 06.022. 768 8

The deficiency of platelet function is the main defect of the hemostatic mechanism during cardiopulmonary bypass, which greatly exacerbates the postoperative bleeding complications. In this study, we assessed, from basic and clinical perspectives, the mechanism of relieving platelet damage by means of aprotinin. In vitro research confirmed that the addition of urokinase (40 U/ml) to platelet-rich plasma and the addition of plasmin (0.3 U/ml) to washed platelets made ristocetin-induced agglutination decline to 31.6% and 38.5% of control values, respectively. The extent of decline was positively correlated with the concentration of urokinase and plasmin. In addition, the platelet membrane glycoprotein Ib decreased to 76.4% of control value. With the addition of urokinase or plasmin to aprotinin-pretreated platelet-rich plasma or washed platelets, the changes in agglutination are not statistically significant and the decrement in glycoprotein Ib is much less marked. Further in vivo research revealed that cardiopulmonary bypass caused a decrease in plasma alpha 2-antiplasmin, indicating the fibrinolytic system activation. Meanwhile, ristocetin-induced agglutination decreased to 39.6% and platelet glycoprotein Ib decreased to 50% of preoperative values. However, with the administration of aprotinin, plasma alpha 2-antiplasmin during cardiopulmonary bypass did not change; platelet agglutination was improved, platelet glycoprotein Ib was preserved, and this consequently resulted in 46% lower blood loss after the operation. The results showed that fibrinolysis impaired platelet function, and this effect may be associated with the hydrolysis of glycoprotein Ib. Fibrinolytic activation occurred during cardiopulmonary bypass and contributed to postoperative platelet dysfunction to a great extent. Aprotinin may inhibit fibrinolysis during cardiopulmonary bypass and thus relieve the platelet damage and improve the postoperative hemostatic mechanism.
J Thorac Cardiovasc Surg 1993 Jul
PMID:Mechanism of the preserving effect of aprotinin on platelet function and its use in cardiac surgery. 768 94

The fibrinolytic system comprises an inactive pro-enzyme, plasminogen, that is converted by plasminogen activators to the active enzyme, plasmin, that degrades fibrin. Two immunologically distinct plasminogen activators have been identified: tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA). Plasminogen activation is regulated by specific molecular interactions between its main components, as well as by controlled synthesis and release of plasminogen activator inhibitors, primarily from endothelial cells. The observed association between abnormal fibrinolysis and a tendency toward bleeding or thrombosis demonstrates the (patho)physiological importance of the fibrinolytic system. Transgenic animals are a suitable experimental model to examine the in vivo impact of fibrinolytic components in thrombosis and thrombolysis. Inactivation, by homologous recombination, of the tissue-type plasminogen activator genes in mice impairs thrombolysis in a significant manner whereas inactivation of the plasminogen activator-1 gene enhances the rate of spontaneous lysis. Despite their widespread use all currently available thrombolytic agents suffer from a number of significant limitations, including resistance to reperfusion, the occurrence of acute coronary reocclusion and bleeding complications. Therefore, the quest for thrombolytic agents with a higher thrombolytic potency, specific thrombolytic activity and/or a better fibrin-selectivity continues. Several lines of research toward improvement of thrombolytic agents are being explored, including the construction of mutants and variants of plasminogen activators, chimeric plasminogen activators, conjugates of plasminogen activators with monoclonal antibodies, or plasminogen activators from animal or bacterial origin.
Cardiovasc Drugs Ther 1994 Dec
PMID:Novel thrombolytic agents. 774 58

Thirty patients with atherosclerotic stenoses or occlusions of iliofemoral arteries were treated from the contralateral approach using a newly designed J-shaped sheath. Seven patients with stenoses and one with an occlusion were successfully dilated with balloon angioplasty. Twenty-two patients with occlusions were treated with urokinase infusion, 16 of whom received coaxial infusion with the J-shaped sheath and catheter. Complete thrombolysis was achieved in 18 patients. The treatment success rate was 100% in the stenotic group and 83% in the occlusion group. Initially, J-shaped sheaths were useful for treatment of iliofemoral artery lesions from the contralateral femoral artery.
Cardiovasc Intervent Radiol
PMID:Crossover approach with a J-shaped sheath for angioplasty of iliofemoral artery stenoses and occlusions. 777 96

Prolonged intravascular infusion of urokinase has proven beneficial in reestablishing patency of chronically occluded peripheral arteries and saphenous vein grafts. This study was performed to assess the efficacy and safety of prolonged urokinase infusion as a prelude to angioplasty in chronically occluded native coronary arteries, that had failed standard angioplasty techniques. Twenty-five patients with objective evidence for ischemia in the distribution of a chronic coronary occlusion were referred for percutaneous intervention. Patients were assessed for any potential exclusions from lytic therapy. Urokinase infusion through both a SOS wire and a stable guiding catheter was continued at 100,000-240,000 units/hr for 8-25 hr; patients then underwent attempted balloon angioplasty. Mean duration of urokinase infusion was 20.6 +/- 7.7 hr (total dose 163,000 +/- 52,447 units/hr). Fibrinogen levels dropped slightly with this (300 +/- 129 to 203 +/- 81 mg/dl, P = 0.02). Angiography posturokinase showed improvement in 7 (28%) with regard to coronary flow (> or = 1 TIMI-grade). Angioplasty was successful in 13 (52%), with final angiographic result revealing thrombus in 5 (20%), or dissection 8 (32%). The infusions were well-tolerated with a low incidence of chest pain, 2 (8%) or ischemic ECG response, 2 (8%); myocardial infarction, 2 (8%); or significant bleeding 2 (8%). All patients survived the procedure, with a length-of-hospital stay = 5.1 +/- 4 days. Use of prolonged preangioplasty intracoronary urokinase infusion can be done safely with success in roughly one-half of patients with chronic total native coronary occlusions who have failed prior attempts at percutaneous intervention.(ABSTRACT TRUNCATED AT 250 WORDS)
Cathet Cardiovasc Diagn 1995 Feb
PMID:Prolonged urokinase infusion for chronic total native coronary occlusions: clinical, angiographic, and treatment observations. 778 87

Abrupt thrombotic stent closure remains a difficult problem to treat in the cardiac catheterization laboratory. A 63-yr-old white female initially underwent successful placement of a Palmaz-Schatz biliary stent in the proximal RCA following failed coronary angioplasty. One week later, the patient represented with an acute inferior infarction and thrombotic occlusion of the stent site in spite of adequate anticoagulation. A new, local drug infusion catheter (the Dispatch catheter) was placed at the angioplasty site and 150,000 units of urokinase were locally infused, with immediate restoration of normal distal flow and a subsequent marked decrease in angiographic thrombus. A small, residual thrombotic filling defect was further treated with a urokinase-coated hydrogel balloon (Hydro Plus). Following local urokinase delivery with the Dispatch catheter and hydrogel balloon, there was complete resolution of angiographic thrombus with TIMI 3 flow and no evidence of distal embolization or no-reflow. Local urokinase delivery directly to the site of thrombus with catheter-based drug delivery systems may be a useful technique for rapidly lysing intracoronary clot and re-establishing coronary flow in the setting of acute stent thrombosis.
Cathet Cardiovasc Diagn 1995 Feb
PMID:Treatment of acute stent thrombosis with local urokinase therapy using catheter-based, drug delivery systems: a case report. 778 94

The objective of this study was to evaluate the efficiency of multiple vascular reconstructive procedures in the presence of an occluded synthetic graft. Over a four year period seventy-seven occluded synthetic grafts were treated with urokinase and reconstruction. Follow-up ranged from 1 to 1627 days (4 years, 5 1/2 months). Kaplan-Meier and generalized Wilcoxon test were used to determine patency and limb salvage rates. The cases were divided into three groups according to the number of previous reconstructive events. Group I consisted of patients that had undergone one previous vascular reconstructive procedure. Group II consisted of patients that had undergone two previous vascular reconstructive procedures. Group III consisted of patients who had undergone three or more previous reconstructive procedures. In Group I, the one, two, and three year patency rates were 48.6%, 34.7%, and 26.0% and the limb salvage rates were 76.2%, 67.9%, and 67.9% for one, two, and three years respectively. The Group II patency rates were 41.9%, 24.4%, and 16.3% and the limb salvage rates were 73.7%, 66.3%, and 66.3%. The Group III patency rates were 31.8%, 5.5%, and 5.5% and the limb salvage rates were 76.6%, 54.8%, and 54.8%. The patency rate was significantly reduced when Group III was compared to Group I (p < 0.01). There was no statistically significant difference in limb salvage rates between any of the groups. These results indicate that the number of secondary vascular reconstructive procedures combined with thrombolysis had no correlation with the prognosis of limb salvage.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cardiovasc Surg (Torino) 1994 Aug
PMID:Evaluation of multiple vascular reconstructive procedures with synthetic graft occlusions. 792 43


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