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

The effect of delayed thrombolysis with recombinant tissue plasminogen activator was tested in an embolic stroke model. The carotid territory was embolized in 103 rats with fibrin-rich clots formed and washed in polyethylene tubes. Hemispheric cerebral blood flow before and after embolization was measured by the intra arterial 133Xe injection method. At five delay times, 15-240 min after embolization, 69 animals were treated with tissue plasminogen activator, 20 mg/kg, and 34 animals with saline. Carotid angiography displayed the grade of occlusion of the cerebral arterial supply before and after treatment. Brains were fixed after 2 days, evaluated neuropathologically, and infarct volume measured. Cerebral blood flow was reduced by 56-71% after embolization. Reperfusion induced by thrombolytic therapy was demonstrated by comparing the posttreatment angiography of the pooled five treatment groups to control animals. Thrombolytic therapy significantly reduced the infarct volume and improved the prekill clinical score by up to 2 h of treatment delay, and treatment might have been beneficial even after 4 h delay. Prolonging the delay of treatment increased the infarct volume (p < 0.001, Jonck-heere-Terpstra test). Only a few hemorrhagic complications were observed. Thus, thrombolytic therapy in embolic stroke induced recanalization. The effect on clinical outcome and infarct volume was dependent on delay time.
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PMID:Effect of delayed thrombolysis with rt-PA in a rat embolic stroke model. 816 89

The physiology of thrombi and the pharmacology of thrombolytic drugs are under active study and improved regimens for the dosing of thrombolytic agents have been developed. In the setting of myocardial infarction, recently reported differences among thrombolytic agents have been slight, including the frequency of thrombolysis-associated hemorrhagic stroke following tissue plasminogen activator or streptokinase. In the setting of ischemic stroke, recanalization rates following intravenous tissue plasminogen activator have been modest and at least partly dependent on clot size. Conclusions regarding clinical benefit will depend on the results of multicenter randomized trials that should available in 1995. Studies of locally administered intra-arterial thrombolytic therapy demonstrate high rates of clot lysis, but clinical benefits have yet to be established. The results of randomized trials will be important in clarifying any cause-effect relationships between thrombolytic therapy and symptomatic and asymptomatic intracranial hemorrhage. Thrombolytic therapy in the study of subarachnoid hemorrhage is under active investigation.
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PMID:Thrombolytic therapy for stroke. 817 73

Treatment with recombinant tissue plasminogen activator (rt-PA) has been applied in acute cardioembolic stroke to reopen the occluded vessel and improve the patient's neurologic deficit. However, the effect of this therapy on intracardiac thrombus has not been documented previously. A forty-five-year-old man with dilated cardiomyopathy developed acute cardioembolic stroke with disturbance of consciousness, right hemianopia, right hemiplegia, and global aphasia. Cerebral angiography demonstrated occlusion of the left middle cerebral artery trunk. Intravenous administration of 30 megaunits (MU) of recombinant tissue plasminogen activator was commenced two hours after the ictus and completed within sixty minutes. Cerebral angiography was repeated just after this treatment and demonstrated a new occlusion of the left intracranial internal carotid artery along with occlusion of a branch of the left external artery. The authors subsequently performed two-dimensional echocardiography and found a mobile thrombus in the left ventricle. In patients with intracardiac mobile thrombi, recombinant tissue plasminogen activator seems to accelerate breakup or detachment of the thrombi and subsequent recurrent embolization. Therefore, it seems better to pay attention to the presence of mobile intracardiac thrombus before commencing intravenous infusion of rt-PA.
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PMID:Recurrent embolization during intravenous administration of tissue plasminogen activator in acute cardioembolic stroke. A case report. 820 76

Efficacy and safety of combined alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor blockade and thrombolytic therapy with human recombinant tissue plasminogen activator (TPA) was tested in a rat embolic stroke model. Sixty-three rats were embolized in the right internal carotid territory with a 200 microliters suspension of microclots formed by alternate moving of 150 microliters whole blood and 50 microliters of thrombin between two interconnected syringes for 4 min. Sixteen embolized rats served as controls, and 16 rats were treated with NBQX immediately after embolization. Thirty-one rats were treated with TPA 2 h following embolization, and in 16 of these rats additional NBQX treatments were initiated 90 min following embolization. Hemispheric cerebral blood flow (CBF) was measured by an intraarterial 133Xenon injection method before and after embolization. Carotid angiography displayed the rate of occlusion of the cerebral arterial supply before and after treatment. Brains were fixed after 2 days, evaluated neuropathologically, and infarct volumes were measured. Median CBF was reduced by 70-77% in the affected hemispheres following embolization. Significant recanalization occurred in all groups except those treated with NBQX. TPA-treated rats had significantly better reperfusion compared to controls judged by angiography 3 h following embolization (P = 0.04). NBQX alone and TPA alone caused insignificant reduction in infarct volume but, when combined, total infarct volume was reduced by 77% compared to controls (P = 0.02). Separate measurement of cortical infarct revealed significantly smaller infarcts (P = 0.05) in the combined treatment group compared to the TPA treatment group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Enhancing the efficacy of thrombolysis by AMPA receptor blockade with NBQX in a rat embolic stroke model. 827 37

Thrombolytic therapy has been proposed in the treatment of cerebrovascular occlusive disease. Early clinical experiences with Urokinase and Streptokinase raised concern about the risk of hemorrhagic complications. More recently, tissue plasminogen activator (tPA) has been evaluated experimentally with promising results. Its clinical utilization has been recently initiated. A review of experimental and clinical data on thrombolysis in cerebral ischemia is presented. TPA treatment produced recanalization and clinical improvement in several patients. The rate of intracranial hemorrhagic complications is similar to the incidence of spontaneous hemorrhagic conversion of ischemic infarction. Nevertheless, large placebo-controlled clinical trials are necessary to further define the efficacy and the optimal modality of administration of tPA in thromboembolic stroke.
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PMID:Thrombolysis in cerebral ischemia. A review of clinical and experimental data. 830 72

In the period from October 1990 to December 1991, 23 patients with acute ischemic stroke were treated with recombinant tissue plasminogen activator (rt-PA) at a median of 205 min (range 78-355 min) after symptom onset. In this open pilot study rt-PA was given intravenously after an acute CT scan had not shown acute changes. In 12 patients regional cerebral blood flow was measured intravenously using 99mTc-HMPAO before and within 24 h after thrombolytic therapy. Reperfusion of the ischemic area was obtained in 10 patients. In these patients clinical improvement was greater the shorter the delay from symptom onset to initiation of treatment. Three of the 23 patients died, one of a parenchymatous hematoma, one of a large middle cerebral artery infarct, and one of acute myocardial infarction.
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PMID:Alteplase therapy in acute ischemic stroke: a Danish pilot study.OFF. 832 85

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

The use of first generation plasminogen activators, urokinase, streptokinase and tissue plasminogen activator has revolutionized thrombolytic therapy for myocardial infarction and ischaemia, and potentially stroke. However, thrombolytic therapy employing these activators is limited by reocclusion of the very arteries being opened, which follows in a small but significant number of patients. The development of second generation plasminogen activators, e.g. staphylokinase and anisoylated plasminogen streptokinase activator complex, has not alleviated the problems encountered with classical plasminogen activators. It is now widely recognized that aberrant platelet aggregation induced primarily by thrombin, rather than plasmin, is one of the major causes of recurrent thrombosis following pharmacologic thrombolysis. Agents that (a) inhibit enzymatic and/or coagulant activity of thrombin, (b) block binding of thrombin to its receptor, and (c) interfere with the generation of thrombin by the prothrombinase complex may compromise haemostasis resulting in haemorrhage. We recently demonstrated that thrombin-induced platelet aggregation is accompanied by cleavage of aggregin, a putative ADP-receptor on the platelet surface, and that these events are indirectly mediated by intracellularly activated calpain expressed on the surface. In this review, we discuss the known mechanisms of thrombin-induced platelet aggregation and suggest relative advantages of potential pharmacological agents, being developed in our laboratory, over those that have been previously developed and tested. These inhibitors selectively prevent aggregation of platelets induced by thrombin by inhibiting calpain expressed on the surface. Moreover, one of these inhibitors which blocks thrombin-induced platelet aggregation does not interfere with other platelet responses mediated by thrombin or platelet aggregation induced by other agonists, such as, ADP, collagen, phorbol myristate acetate and thromboxane A2 mimetics. This selectivity could reduce the chances of perturbing the formation of a haemostatic plug.
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PMID:Reocclusion after thrombolytic therapy: strategies for inhibiting thrombin-induced platelet aggregation. 832 74

Thrombolytic therapy with recombinant tissue plasminogen activator was tested in an embolic stroke model. In rats the internal carotid territory was embolized through the internal carotid artery with 50 microliters thrombin-rich (n = 18), 50 microliters thrombin-poor (n = 17) and 20 microliters thrombin poor (n = 13) suspension of arterial-like microthrombi formed under pressure. Hemispheric cerebral blood flow before and after embolization was measured by intra-arterial 133Xe injection method. Fifteen minutes after embolization 19 animals were treated with tissue plasminogen activator 20 mg kg-1, and 22 animals with saline. Carotid angiography displayed the degree of occlusion of the cerebral arterial supply before and after treatment. Brains were evaluated neuropathologically and infarct volume measured. Cerebral blood flow was reduced 72% after embolization with 50 microliters emboli suspension and 32% after embolization with 20 microliters suspension. The comparison of pre- and post-treatment angiography showed some recanalization in the treated animals, control animals had no recanalization. Thrombolytic therapy reduced the infarct volume from 72.8% to 20.9% of embolized hemisphere volume (p = 0.0037) in the 50-microliters thrombin rich-embolized group, from 22.9 to 9.0 (NS) in the 50-microliters-thrombin-poor-embolized group and from 6.6 to 0.0 (NS) in the 20-microliters-embolized group. One third of treated animals recanalized completely and developed smaller (p = 0.03) infarcts than the non-recanalized. No hemorrhagic complications were observed. Early thrombolytic therapy reduced infarct volume after embolic stroke in this model, this effect was dependent upon recanalization.
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PMID:Reduction of infarct volume by thrombolysis with rt-PA in an embolic rat stroke model. 837 42

A group of 59 patients with stroke due to acute vertebrobasilar or carotid territory occlusion have been treated by local intra-arterial fibrinolysis (LIF). A high recanalisation rate was accomplished with either urokinase or recombinant tissue plasminogen activator (r-TPA). However, with either substance, even if a high dose was used, recanalisation was a time-consuming process which usually took 120 min. A reasonable explanation for the lack of effectiveness of these plasminogen-activating substances might be a deficit of substrate, e.g. plasminogen, in aged thrombus. LIF was capable of improving clinical outcome in acute vertebrobasilar artery occlusion, reducing mortality to 50% in patients fulfilling inclusion criteria. In the carotid territory multiple occlusions had a poor prognosis while good clinical results could be achieved in occlusions of the proximal middle cerebral artery or single branches.
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PMID:Local intra-arterial fibrinolytic therapy in patients with stroke: urokinase versus recombinant tissue plasminogen activator (r-TPA). 843 96


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