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

The incidence of in-hospital stroke complicating acute myocardial infarction is approximately 1%. This rate is largely unaffected by thrombolytic therapy. Large myocardial infarctions, anterior wall involvement, prior stroke, and increasing age are risk factors for ischemic stroke. Left ventricular thrombi commonly occur with anterior wall infarctions. There is some evidence that anticoagulation reduces their incidence and uncontrolled studies suggest that anticoagulation may reduce the risk of embolization. Left ventricular aneurysms have a low rate of embolization and do not require systemic anticoagulation. Treatment of acute myocardial infarction with t-PA and anisoylated plasminogen streptokinase activator complex are associated with a higher risk of stroke than treatment with streptokinase; this excess risk is attributable to an increased rate of cerebral hemorrhages.
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PMID:Coronary artery disease, myocardial infarction, and brain embolism. 831 93

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

The dose-dependent effects of tissue-type plasminogen activator (t-PA) on the kinetics of cerebral clot lysis in a rabbit model of middle cerebral artery embolic stroke were investigated. The clots were formed in vitro and tagged with 99Tc for gamma-scintigraphic imaging. After embolization, groups of animals were treated with t-PA. Dose-response curves for the t-PA were generated, and in addition, long and short dosing schedules were assessed. The optimal doses for frequency and rate of cerebral clot lysis in this model are approximately 6.3 mg/kg given over 2 hr or 3.3 mg/kg given over 30 min. These dosing regimens for t-PA were accompanied by approximately 50% consumption of plasma plasminogen, fibrinogen and alpha 2-antiplasmin. Doses of t-PA on either side of this optimum caused attenuation in both the frequency and rate of cerebral clot lysis. Treatment with t-PA under either dosing regimen did not augment the frequency of hemorrhagic transformation, but the size of the resultant hemorrhage in those animals where intracranial bleeding occurred was reduced by 3.3 mg/kg t-PA given over 30 min.
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PMID:Optimized thrombolysis of cerebral clots with tissue-type plasminogen activator in a rabbit model of embolic stroke. 842 52

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

The 4 widely available thrombolytic agents, alteplase (recombinant tissue plasminogen activator, rt-PA), anisoylated plasminogen streptokinase activator complex (APSAC; anistreplase), streptokinase and urokinase have revolutionised the treatment of acute myocardial infarction and are also effective in treating pulmonary embolism and peripheral arterial thrombosis. Therapeutic efficacy of the agents appears to be similar. Choice of a thrombolytic agent depends more on patient characteristics, availability and familiarity with the drug, cost and differences in tolerability. While overall thrombolytic therapy is relatively safe, these 4 agents differ in their tolerability profiles. Streptokinase has the lowest cerebral haemorrhage rate, anistreplase an intermediate and alteplase the highest rate. The incidence of total stroke is also higher with alteplase and anistreplase than with streptokinase, translating to an actual difference in patient risk of 4 extra strokes per 1000 patients treated. Risk of major bleeding is dependent on predisposing factors and seems to be similar with each agent. The incidence of hypotension with alteplase (4.3% in ISIS-3) is less than with streptokinase or anistreplase (6.8 and 7.2%, respectively in ISIS-3). The incidence of major anaphylactic reactions with streptokinase and anistreplase is low (< 1%). Urokinase and alteplase may be preferred for readministration of thrombolytic therapy and anistreplase is the agent of choice where rapid completion of therapy is desirable. The various agents may have different tolerability profiles with different adjunctive therapies and further data are therefore required.
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PMID:Comparative tolerability profiles of thrombolytic agents. A review. 847 Nov 85

Intravenous heparin is routinely given after thrombolytic therapy for patients with acute myocardial infarction in the United States and in some, but by no means all, other countries. Several trials have documented improved infarct-artery patency in patients treated with heparin; however, none was large enough individually to assess the effect of heparin on clinical outcomes. We performed a systematic overview of the 6 randomized controlled trials (1,735 patients) to summarize the available data concerning the risks and benefits of intravenous heparin versus no heparin after thrombolytic therapy. Mortality before hospital discharge was 5.1% for patients allocated to intravenous heparin compared with 5.6% for controls (relative risk reduction of 9%, odds ratio 0.91, 95% confidence interval 0.59 to 1.39). Similar rates of recurrent ischemia and reinfarction were observed among those allocated to heparin therapy or control. The rates of total stroke, intracranial hemorrhage, and severe bleeding were similar in patients allocated to heparin; however, the risk of any severity of bleeding was significantly higher (22.7% vs 16.2%; odds ratio 1.55, 95% confidence interval 1.21 to 1.98). There was no significant difference in the observed effects of heparin between patients receiving tissue-type plasminogen activator and those receiving streptokinase or anisoylated plasminogen streptokinase activator complex, or between patients who did and did not receive aspirin. The findings of this overview demonstrate that insufficient clinical outcome data are available to support or to refute the routine use of intravenous heparin therapy after thrombolysis. It is not known if these findings are due to lack of statistical power, inappropriate levels of anticoagulation, or lack of benefit of intravenous heparin. Large randomized studies of heparin (and of new antithrombotic regimens) are needed to establish the role of such therapy.
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PMID:Overview of randomized trials of intravenous heparin in patients with acute myocardial infarction treated with thrombolytic therapy. 861 Jun 1

The fibrinolytic system is thought to be impaired in older hypertensive adults, thus contributing to the elevated risk of atherothrombosis, stroke, and acute myocardial infarction in this population. However, studies that have examined the fibrinolytic system in hypertensive individuals have failed to control for the confounding effects of other metabolic risk factors, making it difficult for one to determine the independent effect of hypertension on the fibrinolytic system. The purpose of the present study was to test the hypothesis that the fibrinolytic system is not impaired in older sedentary hypertensive men when the confounding effects of cardiovascular disease, diabetes, and dyslipidemia are controlled. Plasma concentrations of tissue-type plasminogen activator antigen and activity as well as plasminogen activator inhibitor-1 antigen and activity were measured under resting conditions in 12 hypertensive (69.4 +/- 1.4 years) and 11 normotensive 65.2 +/- 1.3 years) older men. The hypertensive and normotensive subjects had similar anthropometric and metabolic characteristics. There were no significant differences between the hypertensive and normotensive men in tissue-type plasminogen antigen (7.3 +/- 0.5 versus 6.1 +/- 0.6 ng/mL) and activity (1.8 +/- 0.3 versus 1.7 +/- 0.2 IU/mL) or plasminogen activator inhibitor-1 antigen (14.1 +/- 2.3 versus 10.8 +/- 2.2 ng/mL) and activity (17.4 +/- 1.2 versus 17.5 +/- 1.8 arbitrary units [AU]/mL) levels. In addition, the molar concentration ratio of active tissue type plasminogen activator to active plasminogen activator inhibitor-1 did not differ between the hypertensive (1:9.7 +/- 2.3) mmol/L) and normotensive (1:10.5 +/- 2.2 mmol/L) subjects, indicative of no impairment in fibrinolytic potential in either group. These results support the hypothesis that hypertension does not directly result in impaired fibrinolytic function in older adults. Furthermore, our findings suggest that abnormalities in fibrinolytic function in older hypertensive men are likely due to the primary effects of other metabolic disorders that usually accompany hypertension, such as hyperinsulinemia and dyslipidemia.
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PMID:The fibrinolytic system is not impaired in older men with hypertension. 862 Nov 96

Cerebral infarction initiates a cascade of molecular events, leading to proteolytic cell death. Matrix-degrading metalloproteinases (MMPs) are neutral proteases involved in extracellular matrix damage. Type IV collagenase is an MMP that increases cerebral capillary permeability after intracerebral injection and may be important along with plasminogen activators (PA) in secondary brain edema in stroke. Therefore, we measured MMPs and PAs in spontaneously hypertensive (SHR) or Wistar-Kyoto (WKY) rats with permanent middle cerebral artery occlusion (MCAO). Brain tissue was assayed for MMPs and PAs at 1, 3, 12, and 24 h and 5 days after occlusion, using substrate gel polyacrylamide electrophoresis (zymography). SHR showed an increase in 92-kDa type IV collagenase (gelatinase B) in the infarcted hemisphere compared with the opposite side at 12 and 24 h (p < 0.05). Gelatinase A remained the same in both infarcted and normal tissue until 5 days after injury, when it increased significantly (p < 0.05). Urokinase-type PA was increased significantly at 12 and 24 h and 5 days, while tissue-type PA was decreased significantly at 1, 12, and 24 h in the ischemic compared with the nonischemic hemisphere. Gelatinase B was markedly increased in SHR at 12 and 24 h compared with WKY (p < 0.05). Secondary vasogenic edema is maximal 1-2 days after a stroke, which is the time that gelatinase B was elevated. The time of appearance of gelatinase B suggests a role in secondary tissue damage and vasogenic edema, while gelatinase A may be involved in tissue repair.
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PMID:Proteolytic cascade enzymes increase in focal cerebral ischemia in rat. 862 40

Lipoprotein(a) (Lp[a]) consists of a LDL-particle and an apolipoprotein(a) which is related to plasminogen. The physiological function of Lp(a) is largely unknown, but the clinical effects are well known: high plasma concentrations of Lp(a) correlate with a high risk for atherosclerosis independently from other risk factors. This was shown in several studies for coronary heart disease, stroke and peripheral atherosclerosis. Lp(a) has a special position within other risk factors because of the strict genetic control of the plasma concentrations by the apo(a) gene locus on chromosome 6q2.6-2.7. Studies which doubt this relationship have to be considered sceptically. Recent investigations with genetic markers confirm that Lp(a) is a risk factor for atherosclerotic vascular diseases.
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PMID:[Lipoprotein(a)--atherogenic waste product of evolution?]. 865 Sep 38


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