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)

To treat severe painful digital ulcers on progressive systemic sclerosis (PSS) patients, we developed a new combination therapy which included neural blockade, intravenous urokinase, and prostaglandin E1 infusion. All of these are already recognized treatments for circulatory disturbances in PSS. Although each of them alone has a limited effect on the painful ischemic attack in PSS; in stepwise combination, neural blockade for release of vascular spasm and pain, prostaglandin E1 for further vasodilatation, and urokinase for thrombolysis were effective in the treatment of digital ischemia in two PSS patients. This therapy reduced the necrotic areas predicted before therapy and saved fingers from amputation. It also relieved the intolerable digital pain and effected the recovery of digital function.
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PMID:Neural blockade, urokinase and prostaglandin E1 combination therapy for acute digital ischemia of progressive systemic sclerosis. 779 34

This is a case report of a 47-year-old man admitted with a 7-month history of disequilibrium, multiple reversible vertebrobasilar ischemic attacks, and one submaximal completed stroke in the left posterior inferior cerebellar artery distribution. Vertebrobasilar ischemic attacks continued despite anti-coagulation, and orthostatic symptomatology suggested a significant hemodynamic component contributing to the posterior circulation ischemia. Angiography confirmed bilateral high-grade stenoses of the intracranial vertebral arteries. A right intracranial vertebral artery endarterectomy was performed with electroencephalographic and somatosensory evoked potential monitoring and protection with barbiturate infusion. The arteriotomy was closed with a vein patch. Postoperatively, the endarterectomy site thrombosed. This thrombosis was completely reversed with 220,000 U of urokinase selectively infused intra-arterially at the site of thrombosis. This procedure was not complicated by hemorrhage or distal embolization. The vertebral artery was confirmed to be patent 24 hours and 7 days after the urokinase injection. The patient sustained a borderzone infarction in the right cerebellar hemisphere without neurological deficits and was discharged home well.
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PMID:Successful treatment of an acute thrombosis of an intracranial vertebral artery endarterectomy with urokinase. 783 54

Case reports of three patients presenting with acute limb-threatening lower extremity ischemia as a result of thrombosed popliteal artery aneurysms are described. Intra-arterial urokinase was administered to each patient prior to definitive surgery. This improved the infrapopliteal runoff in each case, allowing for successful arterial reconstruction without limb loss.
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PMID:Intra-arterial thrombolytic therapy in the initial management of thrombosed popliteal artery aneurysms. 794 62

This study reports the results and complications of local thrombolytic therapy of 50 recently occluded grafts. These occurred in 41 patients with acute severe but still reversible ischemia. The majority were infra-inguinal synthetic grafts. Thrombolysis was induced with urokinase (n = 1), streptokinase (n = 11) or alteplase (n = 38) via an intra-arterial catheter. Complete angiographical lysis was obtained in 36 grafts (72%) and partial lysis in 6 (12%). The highest lysis rate was obtained with alteplase (32/36; 89%). Complementary endovascular and/or surgical intervention was needed in 17 patients to correct an underlying stenosis and/or to save the limb. Fifteen complications occurred (30%) of which distal embolization (n = 4) and bleeding (n = 8 of which 3 fatal) were the most frequent. Six of the bleeding episodes occurred in patients on chronic aspirin intake. The late results were poor. At six months, the primary patency of successfully lysed grafts dropped to 19% and the limb salvage rate to 64%. Thrombolytic therapy is far from the ideal management of thrombosed grafts: maintenance of restored patency is the challenge.
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PMID:Local thrombolysis for occluded arterial grafts: is the yield worth the effort? 804 Jan 65

In order to determine the effect of altering the method of delivery of lytic therapy, both hind limbs of 55 adult mongrel dogs were embolized to occlusion and divided into six different treatment groups. Each right limb received 100,000 units of urokinase (UK) intraarterially by one of six different treatment protocols: Group I (n = 10), 5-min infusion with control of arterial inflow (IC); Group II (n = 10), 5-min infusion without IC; Group III (n = 10), 30-min infusion with IC; Group IV (n = 10), 30-min infusion without IC (simulates percutaneous infusion); Group V (n = 10), isolated limb perfusion (ILP) with femoral arterial and venous cannulation and proximal tourniquet control using an extracorporeal circulating pump at a controlled rate and constant temperature (37 degrees C) for 30 min; Group VI (n = 5), underwent ILP without urokinase. A morphometric score was used to quantitate angiographic changes. Films were compared before and after treatment and the net difference for each animal was recorded. [table: see text] We conclude that maintenance of blood flow during urokinase infusion enhances its effectiveness and, contrary to previous recommendations, during intraoperative delivery, inflow should be maintained. Isolated limb perfusion alone was as effective as a 30-min infusion of urokinase without inflow control. Isolated limb perfusion plus UK was by far the most effective method of administering lytic therapy. These experiments suggest that the mechanical action of flowing blood enhances clot dissolution and significantly increases the effectiveness of pharmacologic lysis. Isolated limb fibrinolytic perfusion may have clinical potential in the surgical treatment of limb ischemia.
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PMID:Isolated limb thrombolysis with extracorporeal pump and urokinase. 807 81

In a retrospective study, we analyzed our experiences in 24 patients with acute ischemia from popliteal artery aneurysms over a period of 27 years and evaluated the value of a preoperative lytic therapy as an adjunct to surgical revascularization, compared to surgery alone. Preoperative urokinase therapy revealed a satisfactory improvement of the runoff in all cases. Follow-up angiography showed complete lysis in 6 and incomplete lysis in 3 of 9 patients. In contrast, in patients treated by surgery alone, postoperative angiography showed residual clots in all cases. The overall amputation rate was 25% (6/24) in 24 popliteal aneurysms with acute ischemia, including four patients with primary amputation for irreversible gangrene. Bypass grafting alone resulted in an early amputation rate of 9% (1/11) and occlusive complications of 45% (5/11) compared to no limb loss and no bypass complication in patients who underwent combined surgery and preoperative lysis (0/9). Our results underline the value of preoperative lytic therapy as an important factor in the management of acute ischemia in popliteal artery aneurysms.
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PMID:The value of preoperative lytic therapy in limb-threatening acute ischemia from popliteal artery aneurysm. 808 57

Intra-arterial thrombolytic therapy is an important advance in the treatment of arterial occlusive disease. Reports of results, morbidity, and mortality have been highly variable. This review was undertaken to assess the recent results of thrombolytic therapy with urokinase (UK) at our institution. From 1988-1992, 42 lower extremities in 41 patients with severe peripheral vascular disease underwent intra-arterial thrombolytic therapy. Sites of occlusion consisted of 6 iliac, 21 superficial femoral, 11 popliteal, and 20 infra-popliteal segments. Lytic therapy consisted of a regional infusion of UK with concomitant heparin anticoagulation. The most common UK loading dose was 250,000 units (60,000-750,000) followed by a continuous infusion of approximately 100,000 units/hour (60,000-240,000) for up to 72 hours. Technical success, defined as partial or total resolution of the arterial occlusions, occurred in 26 (62%) limbs. A concomitant endovascular procedure was required in 19 extremities following successful lysis. Immediate clinical success, defined as restitution of a distal pulse or increase in ABI > 0.10, occurred in 22 of 26 technically successful procedures. The four clinical failures and all 16 technical failures required either a major amputation or revascularization. There were 18 major complications in 18 patients (43%): seven thromboembolic, two arterial dissections, nine hemorrhagic. Seven hemorrhagic complications required transfusion of 1-6 units of blood, and two deaths occurred due to postprocedural hemorrhage, shock, and myocardial infarction. Hemorrhage was not related either to the dose of UK or the duration of UK infusion. A combination of thrombolysis and endovascular intervention can be of significant benefit in selected patients with extremity ischemia. However, complications are frequent and may be lethal.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Thrombolytic therapy for arterial occlusion: a mixed blessing. 816 Oct 90

The ability of urokinase to salvage experimental flaps after a secondary ischemic insult was investigated in a rat model. Unilateral abdominal island skin flaps based on the superficial inferior epigastric vessels were raised and subjected to either 4 or 6 hours of primary ischemia followed by 12 hours of reperfusion and varying lengths of secondary ischemia. At the conclusion of secondary ischemia, the flaps were perfused with either lactated Ringer's solution or urokinase. One group of flaps served as a control and received no postischemic perfusion washout. The secondary critical ischemia time at which 50% of the flaps failed clinically was greater for flaps perfused with urokinase. Furthermore, the survival rates for all flaps perfused with urokinase were significantly greater than either control flaps or flaps perfused with lactated Ringer's solution (p < 0.05). Flap survival decreased significantly in all groups with increasing primary and/or secondary ischemia time (p < 0.05).
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PMID:Use of urokinase during secondary ischemia in experimental skin flaps. 819 93

Thrombolytic therapy is frequently used for the treatment of peripheral arterial occlusion, but clinical predictors of success have not yet been defined. We prospectively evaluated 80 consecutive patients receiving intra-arterial urokinase for acute (< 14 days) ischemia. Fifty-five patients (69%) were treated for bypass graft occlusion and 25 patients (31%) for native arterial occlusion. Two primary outcome measures were evaluated using multivariate techniques (stepwise logistic regression) to determine the independent predictors of immediate arteriographic success: successful (> 80%) thrombolysis and avoidance of adjuvant operative or endovascular procedures. Independent variables examined included age, sex, comorbid conditions, severity, duration, etiology and location of the ischemic process, and positioning of the infusion catheter and guidewire. Overall, successful lysis was achieved in 57 patients (71%) and adjuvant procedures were avoided in 22 patients (28%). Successful outcome was more frequent in prosthetic graft (78%) and native arterial (72%) occlusions than in vein graft occlusions (53%, p = 0.017) and in nondiabetics than in diabetics (80% vs. 52%, p = 0.031). Lysis was dependent on placement of the catheter into the substance of the thrombus (85% vs. 0% success, p = 0.004) and passage of a guidewire through the occlusive process (92% vs. 10% success, p = 0.001). The only parameter independently predictive of successful outcome without the use of adjuvant procedures was the location of the occlusion; additional procedures were necessary in 88% of aortoiliac and 82% of infrainguinal occlusions vs. only 17% of upper extremity occlusions (p = 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Thrombolysis in acute peripheral arterial occlusion: predictors of immediate success. 819 1

The loss of distal tissue perfusion sufficient for limb salvage following restoration of inflow to an acutely ischemic extremity has been referred to as the "no-reflow" phenomenon. We hypothesized that patients with no reflow and limb-threat ischemia might benefit from prolonged postoperative intra-arterial infusion of the thrombolytic agent urokinase (UK). Twelve patients with arteriographic and clinical evidence of no reflow following a lower extremity arterial thrombectomy and/or bypass procedure were treated with a continuous intra-arterial UK infusion in the immediate postoperative period. The mean duration of UK infusion was 47 hours (range 15 to 112 hours). The mean rate of infusion was 58,000 units/hr (range 30,000 to 100,000 units/hr). Seven patients required transfusion for bleeding from the treated extremity (mean 3.4 units packed cells) and one required reoperation for a groin hematoma. Plasma fibrinogen levels remained within the normal range in all patients, and no systemic bleeding complications were encountered. The intra-arterial UK infusion resulted in limb salvage in 7 of 12 patients. Six patients have viable, functional extremities at a mean follow-up interval of 24.9 months (range 6.4 to 49.7 months). One patient required below-knee amputation 6 months after treatment for progressive ischemia. The other five patients required below-knee amputation during the same hospitalization after UK failed to restore distal perfusion. The postoperative period is widely considered to be a contraindication to thrombolytic therapy. Our experience indicates that while UK may cause bleeding from the treated extremity, which in some cases requires transfusion, there is no evidence of systemic fibrinolysis or systemic hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Continuous postoperative intra-arterial urokinase infusion in the treatment of no reflow following revascularization of the acutely ischemic limb. 819 3


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