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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

All thrombolytic agents convert plasminogen to plasmin, either directly, as in the case of urokinase, saruplase, and alteplase, or indirectly, as in the case of streptokinase. In the majority of recent clinical trials with streptokinase, a high-dose (0.7-1.5 million units), brief-duration (30-90 minutes) drug regimen has been used. After a mean interval of 4.2 hours from onset of chest pain to intravenous infusion of streptokinase, repeat angiography performed 60-90 minutes after the start of thrombolytic treatment gave a reperfusion rate of 43%; the corresponding figures for anistreplase, saruplase, and alteplase are 56%, 67%, and 69%. The patency rates obtained in similar studies with the same end point are 56% for streptokinase, 77% for anistreplase, 62% for urokinase, 71% for saruplase, and 75% for alteplase. The in-hospital mortality in randomized trials (six large studies in a total of 31,713 randomized patients) with intravenous high-dose streptokinase decreased from 12.0% in the control group to 9.47% in the streptokinase group. In a mortality study involving 1,258 patients randomized to intravenous anistreplase or placebo, the 30-day mortality was reduced by 47%, from 12.2% to 6.4%. In a large trial in which 5,011 patients were randomized to alteplase or placebo, the 30-day mortality was 7.2% compared with 9.8% in controls, a reduction of 27% by alteplase. In another trial, 721 patients were randomized to placebo or alteplase; all patients received acetylsalicylic acid and intravenous heparin. The 14-day mortality was only 2.8% in the alteplase group, 51% less than that in the control group. It is most important that the favorable impact on hospital survival be maintained at 1 year for any thrombolytic drug. Large-scale trials directly comparing mortality after alteplase, streptokinase, or anistreplase are being performed or are in the planning phase. The risk of bleeding exists with any thrombolytic agent; intracranial bleeding is the most serious risk. In a large trial in 5,011 patients with acute myocardial infarction, stroke occurred in 1.1% of alteplase-treated patients compared with 1.0% in placebo-treated controls. Haunting problems are residual stenosis of the coronary artery and reocclusion. Urgent angioplasty does not seem to be the right answer; more effective antithrombotic strategies have yet to be developed.
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PMID:Thrombolytic treatment in acute myocardial infarction. 211 32

We conducted a randomized, blinded controlled trial to test the efficacy of fibrinolytic therapy with tissue plasminogen activator and urokinase in the treatment of acute embolic stroke. Embolic stroke was simulated in rabbits by injecting three 0.5 x 0.5 mm fragments of autologous arterial thrombus harvested from a traumatized auricular artery. Thirty minutes after embolization the rabbits were blindly treated with tissue plasminogen activator (n = 21), urokinase (n = 20), or 0.9% saline (n = 20). At 6 hours the rabbits were sacrificed, and the cerebral vasculature was inspected for the location and number of emboli. The brain was then cut into 0.5-cm-thick coronal sections and stained with triphenyltetrazolium chloride to define areas of infarction. Treatment with either tissue plasminogen activator or urokinase significantly reduced the number of emboli present in the cerebral circulation (p less than 0.05). The area of ischemic injury was also significantly reduced (p less than 0.05) by acute fibrinolytic therapy with either tissue plasminogen activator or urokinase. However, only treatment with tissue plasminogen activator significantly reduced (p less than 0.05) the incidence of infarction. There was no evidence of intracerebral hemorrhage in any rabbit. Early fibrinolytic therapy improved outcome in this model of acute embolic stroke.
Stroke 1990 Nov
PMID:Effect of intra-arterial tissue plasminogen activator and urokinase on autologous arterial emboli in the cerebral circulation of rabbits [corrected]. 212 53

Thrombotic disorders such as myocardial infarction and stroke are the leading causes of death and disability in industrialized nations. Timely institution of thrombolytic therapy can achieve a reduction of infarct size, a preservation of left ventricular function, and a reduction in mortality. The administration of streptokinase, urokinase, and acylated plasminogen-streptokinase activator complex (APSAC) can be associated with a complete breakdown of the hemostatic system. Tissue-type plasminogen activator (t-PA) and single-chain urokinase-type plasminogen activator (scu-PA, prourokinase) are more fibrin specific; however, at the large dosages of activator needed for therapeutic efficacy, bleeding complications are still a problem. New approaches to optimizing the risk/benefit ratio for the patient by improving efficacy without sacrificing specificity include the use of synergistic combinations of plasminogen activators, mutants of t-PA and scu-PA, chimeric molecules, and antibody-targeted thrombolytic agents. The last approach opens the possibility of targeting several different components of the clot with either fibrinolytic or antiplatelet effector functions in one optimized molecule.
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PMID:Future directions in plasminogen activator therapy. 218 64

All thrombolytic agents convert plasminogen to plasmin, either directly as urokinase, saruplase and alteplase or indirectly as streptokinase. In the majority of recent clinical trials with streptokinase, a high-dose (0.7 to 1.5 mega-units), brief-duration (30 to 90 minutes) drug regimen has been used. After a mean time interval of 4.2 hours from onset of pain to intravenous infusion of streptokinase, a repeat angiography performed 60 to 90 min after start of thrombolytic treatment gives a reperfusion rate of 43%, the corresponding figures for anistreplase, saruplase and alteplase are 56%, 67% and 69%. The patency rates of similar studies with the same endpoint are for streptokinase 56%, for anistreplase 77%, for urokinase 62%, for saruplase 71% and for alteplase 75%. The reduction in hospital mortality in randomized trials with intravenous streptokinase (high-dose) is in 6 large studies in a total of 23,267 randomized patients from 10.7% in the control group to 7.0% in the streptokinase group. In a mortality study involving 1,004 patients randomized to intravenous anistreplase or placebo the 30-day mortality was reduced by 47%, from 12.2% to 6.4%. A large trial in which 5,011 patients were randomized to alteplase or placebo, the 30-day mortality was 7.2% compared to 9.8% in controls, a reduction of 27% by alteplase. In another trial 721 patients were randomized to placebo or alteplase; all patients were on aspirin. The 14-day mortality was only 2.8%, 51% less than that in the control group. It is most important that the favourable impact on hospital survival is maintained at 1 year with any thrombolytic drug. Large scale trials directly comparing mortality after alteplase, streptokinase or anistreplase are being performed or in the planning phase. The risk of bleeding exists with any thrombolytic agent but intracranial bleeding is the most serious one. In a large trial on 5,011 patients with acute myocardial infarction, stroke occurred in 1.1% of alteplase treated patients compared with 1.0% in placebo treated controls. Crucial problems are residual stenosis of the coronary artery and reocclusion. Urgent angioplasty does not seem to be the right answer; more effective antithrombotic strategies still have to be developed.
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PMID:[Thrombolytic therapy in acute myocardial infarct]. 219 44

Acute upper-extremity arterial occlusion may be due to embolic phenomena or de novo thrombosis. If the occlusion is left untreated, claudication or ischemia necessitating amputation can occur. Operative Fogarty-balloon embolectomy has been the treatment of choice for this entity. In a 6-year period the authors used fibrinolysis on nine occasions in eight patients to treat acute upper-extremity arterial occlusions. Concomitant balloon angioplasty was helpful in four cases. Success, defined as a normal hand with at least one artery that was continuously patent to the wrist, was achieved in all patients. A single significant groin hematoma was seen. Neither stroke nor death occurred in any case, and no amputations were necessary. Local transcatheter intraarterial administration of urokinase can be considered a first-line treatment for brachial artery embolus and other causes of acute upper-extremity arterial occlusion.
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PMID:Fibrinolytic therapy for upper-extremity arterial occlusions. 198 30

Acute fatal pulmonary embolism is one cause of sudden death which should be guarded against. It is the most often missed diagnosis in sudden death cases within the hospital. Clinical pictures of 10 patients with acute fatal pulmonary embolism proved by autopsy were examined to elucidate the problems of diagnosis, and to look for an effective treatment, and a method of prevention. Common risk factors were old age and immobility due to stroke or postoperative state. Common past histories were hypertension, diabetes mellitus, obesity, atrial fibrillation and hyperlipidemia. Electrocardiogram and echocardiogram showed that in these patients there was definite evidence of acute right ventricular overload. High doses of intravenous urokinase should be given whenever acute cardiovascular collapse develops in such high risk patients. Emergent pulmonary angiogram and pulmonary embolectomy could be life-saving in patients with acute massive pulmonary embolism. Prevention is, however, the best treatment. In addition to anticoagulation medication, frequent change of body position and early mobilization are important precautions to prevent fatal pulmonary embolism developing in such patients.
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PMID:[Acute fatal pulmonary embolism: its prevention, diagnosis and treatment]. 236 72

Between 1984 and 1989, 35 patients with recent arterial or graft occlusions have been treated with intra-arterial infusion using sequential association of Urokinase (U.K.) and Lys-Plasminogen. Occlusion was thrombotic in 68.5% of the cases ans embolic in 31.5%, involving 28 native arteries and 7 bypass grafts. The mean duration was 16 days (2 to 90). Continuous infusion of U.K.: 84,000 U.I./H and bolus of Lys-Plasminogen 15 microKatals every 30 minutes were delivered through a catheter embedded into the clot. Intra-venous heparin was always associated. The mean duration of lytic drug infusion was 8 H. Complementary arterial reconstruction by vascular surgery of percutaneous transluminal angioplasty was performed in 23% of the patients. Patients with recent alimentary tract bleeding, hemorragic stroke in the last six months or severe high blood pressures were contra-indicated. Complete lysis was obtained in 23 cases (66%), partial lysis in 7 (20%) and no lysis in 5 (14%). The clinical result was excellent in 24 cases (68.5%), good in 3 (8.5%) and bad in 8 (23%) in which amputation was always necessary. 5 local hematoma (14%) treated by surgery or transfusion and one death (3%) due to neurological complication occurring 24 hours after the end of the procedure were observed. The literature survey has shown that the results of low doses of Streptokinase (S.K.) local infusions were not better, and that higher doses of S.K. or U.K. delivered during a shorter infusion time increased the efficacy of lysis and decreased the rate of hemorragic complications. We have proposed the local thrombolytic treatment to the limb threatening ischemic cases when the traditional medical or surgical techniques where thought to be associated to a high risk of failure or complication. The specific indications are the acute or sub-acute ischemic situation due to atheromatous artery thrombosis, distal or old embolism where the Fogarty catheter is inefficient, and graft thrombosis. Severe acute ischemia with neurologic involvement are not good indications. Local thrombolysis can be successful on arterial occlusion even after one month duration.
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PMID:[Intra-arterial thrombolytic therapy of lower limb ischemia]. 237 17

The oral administration of the thrombolytic agent urokinase was studied. Its intestinal absorption was demonstrated in dogs by the observation of a prolonged urokinase activity in plasma with a concomitant lytic effect on artificial thrombi after intraduodenal administration. In situ intestine-liver perfusion experiments in dogs revealed that a plasminogen activator, distinct from the administered urokinase--thus presumed to be a tissue plasminogen activator--was liberated into the circulation in association with intestinal absorption of urokinase. Its absorption in men was demonstrated in a cross-over double blind study of oral urokinase on healthy subjects. On the basis of these results a double blind clinical trial of oral urokinase was performed on 101 patients with cerebral thrombosis. The results showed the usefulness of urokinase treatment, particularly in the early phase after the onset of stroke. The clinical effect was influenced by the plasma plasminogen level.
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PMID:Oral urokinase: absorption, mechanisms of fibrinolytic enhancement and clinical effect on cerebral thrombosis. 242 93

Recognition that myocardial infarction is caused by coronary thrombosis has stimulated a search for a safe, rapidly acting, and effective thrombolytic regimen. Tissue plasminogen activator (t-PA) can provide relatively clot-selective thrombolysis, but one quarter of patients fail to achieve reperfusion, lysis speed is not optimal, and higher doses have been associated with an increased incidence of hemorrhagic stroke. We report the results of a multicenter study of pro-urokinase, a second naturally occurring plasminogen activator that has structural similarities to t-PA but has a different mechanism of action. Pro-urokinase was administered 3.9 +/- 1.1 hours after the onset of chest pain to 40 patients with acute myocardial infarction with angiographically confirmed complete coronary occlusion (TIMI grade 0). After a 90-minute intravenous infusion of pro-urokinase (4.7-9 million units, 36-69 mg) 51% (20 of 39) of the patients demonstrated reperfusion (TIMI grade 2 or 3) occurring 64.8 +/- 22.3 minutes after initiation of therapy. Fibrinogen levels fell only 10 +/- 17% from baseline, confirming the fibrin specificity of pro-urokinase. As with t-PA, however, this specificity was only relative. alpha 2-Antiplasmin decreased to 39% and plasminogen decreased to 64% of initial values. Fibrinogen degradation products increased 63% and the fibrin-specific D-dimer increased 8.7-fold. Thus, pro-urokinase produces relatively clot-selective coronary thrombolysis similar to that produced by t-PA, but the use of either pro-urokinase or t-PA alone in higher doses would be likely to produce more nonspecific effects.
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PMID:Clot-selective coronary thrombolysis with pro-urokinase. 249 4

Clinical experience with thrombolytics in non-coronary disorders is limited to the plasminogen activators streptokinase, urokinase and alteplase; therapeutic trials with anistreplase (APSAC) are almost, and with saruplase completely, limited to acute myocardial infarction. In terms of thrombus clearance, thrombolytic drugs are superior to heparin in patients with recent deep vein thrombosis in the pelvis or lower limbs. In aggregate, thrombi younger than 8 days are lysed in approximately 60% of patients treated with streptokinase, urokinase or alteplase. The results of studies assessing the subsequent development of the postphlebitic syndrome are conflicting, but most suggest that thrombolytic therapy can reduce symptoms of chronic venous insufficiency. Currently, the combination of systemic thrombolytic drugs followed by heparin is recommended for patients with acute major pulmonary embolism who are haemodynamically unstable. Streptokinase, urokinase and alteplase have all been shown to accelerate the lysis of pulmonary emboli and to decrease pulmonary vascular obstruction and pulmonary hypertension. Systemic venous or intrapulmonary infusions of alteplase offers the same benefit in terms of angiographic and haemodynamic improvement. A short infusion of 100 mg alteplase over 2 hours seems to be superior to a 24-hour infusion of urokinase. None of the thrombolytic trials in pulmonary embolism have been large enough to demonstrate a reduction in mortality. It is now generally accepted that, unless contraindicated, thrombolytic therapy is the front-line treatment for patients with massive pulmonary embolism and major haemodynamic disturbance. The local treatment of acute arterial occlusion in limb arteries results in rapid clearing of the artery in 67% of patients treated with streptokinase; the corresponding success rates for urokinase and alteplase are 81% and 88 to 94%, respectively. The main question appears to be the identification of patients in whom local thrombolysis is the treatment of choice, as opposed to established therapeutic modalities. Thrombolytic treatment following a major ischaemic stroke is hazardous, although clinical improvement has been noted in a minority of patients with recanalised cerebral arteries. The safety and efficacy of thrombolytic treatment remains unproven for this indication, and its use must be restricted to experimental protocols. Thrombolytic treatment in retinal artery or vein occlusion has, in practice, been abandoned.
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PMID:Use of thrombolytic drugs in non-coronary disorders. 268 38


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