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)

Occlusion of a femoral-popliteal or a femoral-tibial bypass graft on a prior occluded superficial femoral artery or the popliteal artery (in cases of ischemia of the legs) creates a complicated problem that may result in limb loss. The revascularization of such limbs with a repeat femoral-tibial or peroneal bypass is difficult and results in a high rate of limb loss from failure of the repeat grafts. Therefore, attempts were made to re-open the grafts through urokinase administration and thrombolysis for the grafts. To address the distal critical stenosis, or occlusion, the urokinase administration and thrombolysis were followed by endovascular endarterectomy using a thromboembolytic catheter (TEC). From 1990 to 1992, the above protocol was followed with 15 patients. In all patients, the protocol included 24 to 48 hours of urokinase administration with 60,000 to 120,000 U of urokinase per hour. A distal pathology was detected in all 15 patients, of whom 8 had complete occlusion at the site of distal anastomosis, 7 had critical stenosis ranging from 90% to 99%, and 1 was found to have a proximal critical stenosis at the femoral-graft junction. TEC catheter endarterectomy was performed to address the problem of occlusion and critically stenosed distal anastomotic lesions; a 100% success rate was immediately achieved, with flow being re-established to the distal limb. Fourteen of 15 patients remained well revascularized for more than 1 year. One patient experienced re-occlusion after 8 months; the occlusion was re-opened using the same technique of urokinase administration and the use of the TEC catheter, in which case the graft subsequently remained open. The longest follow-up of one patient is more than 2 years, during which time the graft has stayed open. With the aforementioned results, after revascularization of the ischemic limbs from occluded bypass grafts, it is strongly recommended that urokinase administration, along with TEC endovascular endarterectomy, be used to establish the circulation when occluded grafts threaten limb loss.
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PMID:Revascularization of the limbs with urokinase and TEC catheter endarterectomy for occluded bypass grafts. 827 63

Isometric contraction to direct supramaximal tetanic stimulation of the anterior tibialis (AT) muscle was measured in 50 New Zealand White rabbits after ischemia and reperfusion. Ischemia was produced unilaterally by collateral ligation and temporary inflow control until AT muscle function decreased to < 5% of contralateral (control) AT muscle and the ischemic interval was recorded. Reperfusion was carried out in one of the following ways: group I (n = 20), release of vascular clamps (blood reperfusion [BR]); group II (n = 10), release of vascular clamps and simultaneous intraarterial administration of 50,000 units of urokinase (urokinase reperfusion [UR]); group III (n = 10), release of vascular clamps and simultaneous administration of 50,000 units of urokinase and 28 mg (5 units) of purified rabbit plasminogen (urokinase plasminogen reperfusion [UPR]); and group IV (n = 10), animals defibrinated to < 50 mg/dl with ancrod prior to ischemia and received BR (ancrod blood reperfusion [ABR]). During reperfusion, function was recorded every 60 min for 2 hr. Recovery of experimental muscle function is expressed as the percentage of contralateral control limb function. The mean ischemic interval (mean +/- SEM), to achieve < 5% of contralateral control limb function, was 206.7 +/- 9.9, 209.5 +/- 16.6, 221.7 +/- 12.5, and 272.0 +/- 14.2 min for animals in groups I-IV, respectively. The mean experimental muscle function (mean +/- SEM) following the ischemic interval was 3.2 +/- 0.8, 4.5 +/- 1.4, 4.4 +/- 1.2, and 3.3 +/- 1.0 for groups I-IV, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of hypofibrinogenemia and fibrinolysis on skeletal muscle function after ischemia and reperfusion. 827 73

Stroke is one of the leading causes of death in the industrial nations of the world. Up to now, there has been no therapeutic strategy available which has been proven by controlled clinical trials. In the majority of acute stroke patients acute thrombosis contributes to carotid and vertebrobasilar arterial occlusions. Therefore, significant interest has focused on the possible value of fibrinolytic therapy in acute stroke. The principal goal is the rapid lysis of occluding thrombus with a minimum risk of intracranial or systemic hemorrhage. Clinical investigations on thrombolysis in cerebrovascular ischemia included different plasminogen-activators such as urokinase, streptokinase, and tissue plasminogen activator, either given systemically or locally via an intraarterial catheter. The pivotal trials conducted so far have revealed a wide range of recanalization rates, an acceptable safety and, also, encouraging effects on neurologic outcome. Thrombolysis itself carries the risk of intracranial bleeding, a practical limitation of this approach in acute stroke. On the other hand, hemorrhagic infarction and parenchymatous hematoma are natural consequences of thromboembolic stroke, possibly as a result of persistent occlusion of an artery. Hemorrhage following thrombolysis seems to show the same features seen in untreated patients and with an incidence similar to that in untreated patients. Future developments in thrombolysis in acute stroke should include improved early recruitment of patients, evaluation of noninvasive techniques in the pretreatment assessment of patients, the evaluation of advanced invasive techniques for delivery of the thrombolytic agent and assessment of combined treatment strategies. Clinical studies evaluating these strategies are currently under way.
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PMID:Thrombolytic intervention in acute thrombotic and embolic stroke. 832 15

Most reports on emergency coronary revascularization deal with failed percutaneous transluminal coronary angioplasty (PTCA) or refractory ischemia which developed after hospital admission. The objective of this study was to evaluate the feasibility and prognosis of emergency revascularization for acute myocardial infarction evolving outside the hospital. Between 1974 and 1992 54 cases were included in this study. The patients had both electrocardiographic and clinical evidence of ongoing ischemia. One or more infarct-related obstructed coronary arteries were documented by emergency angiography. Since 1981, the patients have been given urokinase, and, since 1986, they have undergone PTCA initially and, when reperfusion failed, revascularization was started. Overall in-hospital mortality has been 11.1% (6/54). All other patients were discharged in satisfactory condition. Follow-up for periods of up to nearly twenty years has been uneventful with the exception of two late sudden deaths. The above results confirm that emergency coronary revascularization is a therapeutical option worth considering.
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PMID:Emergency myocardial revascularization for myocardial infarction evolving outside the hospital. A feasible option when thrombolysis and coronary angioplasty have failed. 834 71

A prospective randomized controlled trial compared forced infusion (FI) of urokinase (UK) with conventional slow continuous infusion (CI) in 25 patients with 25 acutely ischemic lower limbs. Demographics, ischemia categories, and infusion rates and doses were similar for both groups. A preliminary single-pass bolus of UK was injected into the thrombus in all patients with a pulsed-spray technique, and heparin was administered. UK was then infused with a CI pump (n = 13) or a prototype pulsed-spray pump (n = 12). The primary end point was patency, defined as at least 95% thrombolysis by volume, with brisk antegrade flow occurring within 4 hours. Eleven of the 12 patients (92%) who underwent FI and nine of the 13 (70%) who underwent CI had patency within 4 hours. However, 10 patients who underwent FI and nine who underwent CI had residual thrombi prolonging infusion. No significant differences between the two groups were apparent in speed of lysis, initial success rates, complication rates, or 30-day clinical outcome. Lytic therapy, however, was completed within 24 hours in 18 of 23 (78%) successfully treated patients (P = .01).
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PMID:Intraarterial thrombolysis of lower extremity occlusions: prospective, randomized comparison of forced periodic infusion and conventional slow continuous infusion. 813 77

A term infant with aortic and renal artery thrombosis is described, in whom the right kidney experienced complete ischemia for 5 days. A continuous intrathrombic urokinase infusion induced complete clot lysis and reperfusion of the right kidney. Follow-up studies of renal function and renal growth have been normal. This is the first report to describe complete pharmacological salvage of a neonatal kidney after prolonged warm ischemia. This case underscores both the ability of the neonatal kidney to recover from prolonged ischemia and the need to effect thrombolysis before irreversible renal injury occurs. The intrathrombic use of fibrinolytic agents in similarly affected infants warrants consideration and further study.
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PMID:Intrathrombic urokinase reverses neonatal renal artery thrombosis. 839 52

Pharmacologic manipulation of free flaps to enhance tolerance to ischemia has become a subject of great interest in the research literature. In an effort to improve survival, perfusion washout of experimental free flaps was performed following an episode of primary ischemia. The perfusates utilized were lactated Ringer's solution (LR), University of Wisconsin solution (UW), a high-molecular-weight medium used in organ preservation, and urokinase, a thrombolytic agent. Seventy-five rats were used in this study and divided into groups of 5 each. A 3 x 6-cm abdominal free flap based on the superficial inferior epigastric vessels was raised in each rat. The free flaps were subjected to either 12 or 18 hr of primary ischemia. Following the period of ischemia, perfusion washout was performed with either LR, UW solution, or urokinase at increasing concentrations alone or in combination with UW solution. Urokinase was first evaluated as a perfusate alone at increasing concentrations. In the 12-hr ischemia group, free-flap survival was shown to increase from 0 percent in the LR-perfused flaps to 20 percent, 60 percent, and 80 percent in flaps perfused with 12,500, 25,000, and 100,000 U of urokinase, respectively (p < 0.05). A similar increase in survival was demonstrated in the 18-hr ischemia group, where 0 percent, 20 percent, and 40 percent of flaps survived following perfusion with 12,500, 25,000, and 100,000 U of urokinase, respectively (p < 0.05). Urokinase was then perfused along with UW solution to evaluate the combined effect on flap survival.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The additive beneficial effect of UW solution and urokinase on experimental microvascular free-flap survival. 851 98

An 80-year-old man with diabetes developed acute ischemia of the right leg secondary to heparin-induced thrombocytopenia while being treated for a pulmonary embolism. For fear of recurrent thrombosis at the operative site, he was treated with cessation of heparin, placement of a Greenfield filter, and intra-arterial infusion of urokinase into the popliteal artery for 36 hours. All arterial thrombus resolved with no complications. One week later he underwent a below-knee popliteal to anterior tibial artery translocated cephalic vein bypass and transmetatarsal amputation for progressive gangrene of the right toes. The graft remains patent 2 years later. This patient represents the eighth case reported in the world literature in which thrombolytic therapy was used to treat arterial thrombotic complications of heparin-induced thrombocytopenia. Five patients were successfully treated without complications, two others required major amputations, and one died of adrenal hemorrhage. Although thrombolytic therapy should be used cautiously for treatment of arterial thrombotic complications of heparin-induced thrombocytopenia, this adjunct may prove useful and safe in selected cases.
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PMID:Thrombolysis to treat arterial thrombotic complications of heparin-induced thrombocytopenia. 852 43

Intraarterial thrombolysis is used increasingly for management of arterial and bypass graft occlusions. Current research has been directed at the indications for and methods of catheter-directed thrombolysis. Streptokinase, urokinase, and tissue plasminogen activator (t-PA) are the most commonly used agents. They are administered by a variety of techniques and in various doses involving intrathrombic infusions, thrombus lacing, high-dose bolus therapy, and pulse-spray lysis. The latter methods appear to produce thrombolysis within a few hours, so this chemical therapy has the potential to become the first-line management for all episodes of acute limb ischemia. The role of thrombolysis is to return patients to their prethrombotic or preembolic state, so the underlying condition can be treated by radiologic intervention, surgery, or anticoagulation. Intraarterial thrombolysis is indicated for occlusions of less than 2 weeks' duration where the limb is able to withstand a period of further ischemia. Older occlusions should be treated by surgery, reserving intraoperative lysis for specific situations.
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PMID:Lower limb intraarterial thrombolysis as an adjunct to the management of arterial and graft occlusions. 866 48

We report a case of the heparin-induced thrombocytopenia and thrombosis syndrome presenting with acute ischemia of a lower limb. The patient was successfully treated by withdrawal of heparin products, intraarterial urokinase, and platelet anti-aggregation therapy consisting of Dextran and aspirin.
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PMID:The heparin-induced thrombocytopenia and thrombosis syndrome: treatment with intraarterial urokinase and systemic platelet aggregation inhibitors. 866 73


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