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

This study was designed to investigate possible diurnal fluctuations in the efficacy of thrombolysis with streptokinase and whether they follow the circadian periodicity which has already been well documented for the time of onset of acute myocardial infarction, transient myocardial ischaemia, sudden cardiac death, thrombotic stroke, and for the efficacy of thrombolysis with tissue-type plasminogen and urokinase. A total of 156 consecutive patients treated with streptokinase were studied retrospectively; success or failure of thrombolysis was determined according to accepted clinical and angiographic criteria. A definite time peak for successful thrombolysis could be detected at the late afternoon and early evening hours; between 16.00 and 20.00 h, 30.2% of all successful thrombolysis cases were observed compared with 7.0% between 20.00 and 24.00 (p < 0.05) or 10.5% between 00.00 and 04.00 (p < 0.05). Between 16.00 and 20.00 h, 75.8% of treated patients had successful thrombolysis compared to 15.2% of failed treatments and 9% equivocal results (p < 0.001). Multiple regression analysis showed that the independent factor with the major impact on successful reperfusion was the actual time of thrombolysis (p = 0.037), followed by the time delay from pain onset to streptokinase administration (p = 0.020), while age and gender had much lesser impact (p = 0.328 and 0.215, respectively) and the individual risk factors even less. These findings may have several clinical implications; dose adjustment for the time of day may be required, with higher doses during morning hours, or preference for primary coronary angioplasty in order to avoid the increase in bleeding complications related to higher doses of thrombolytic agents.
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PMID:Circadian fluctuations in the efficacy of thrombolysis with streptokinase. 1062 77

In focal cerebral ischemia the plasminogen-plasmin system plays a role in the fibrinolysis of vessel-occluding clots and also in the proteolysis of extracellular matrix components, which potentially contributes to brain edema and bleeding complications. The authors investigated the plasminogen activation after middle cerebral artery occlusion with and without reperfusion (reperfusion intervals 9 and 24 hours) in rats by histologic zymography and compared areas of increased plasminogen activation to areas of structural injury, which were detected immunohistochemically. After 3 hours of ischemia, increased plasminogen activation was observed in the ischemic hemisphere. The affected area measured 5.2%+/-8.5% and 19.4%+/-30.1% of the total basal ganglia and cortex area, respectively. Reperfusion for 9 hours after 3 hours of ischemia led to a significant expansion of plasminogen activation in the basal ganglia (68.8%+/-42.2%, P < 0.05) but not in the cortex (43.0%+/-34.6%, P = 0.394). In the basal ganglia, areas of increased plasminogen activation were related to areas of structural injury (r = 0.873, P < 0.001). No such correlation was found in the cortex (r = 0.299, P = 0.228). In this study, increased plasminogen activation was demonstrated early in focal cerebral ischemia. This activation may promote early secondary edema formation and also secondary hemorrhage after ischemic stroke.
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PMID:Plasminogen activation in focal cerebral ischemia and reperfusion. 1069 71

Polymorphonuclear leukocytes are activated in acute ischemic stroke. Activated polymorphonuclear leukocytes may contribute to thrombolysis by proteolytic degradation of fibrin and by modification of the plasminogen system. We used an in vitro thrombolysis model to investigate (1) thrombolytic properties of leukocytes in young and healthy subjects, (2) to test the hypothesis of increased polymorphonuclear leukocyte-associated thrombolysis in patients with acute cerebral ischemia, and (3) to assess plasminogen-dependent and -independent thrombolytic properties of polymorphonuclear leukocyte elastase. Coincubation of polymorphonuclear leukocytes with fibrin clots led to increased thrombolysis, a process reaching statistical significance after 8 hours [1x10(7) polymorphonuclear leukocytes/mL; 12.8+/-1.9% (mean+/-SEM), spontaneous clot lysis: 7.3+/-0.7%]. Polymorphonuclear leukocytes inside clots caused more efficient thrombolysis than polymorphonuclear leukocytes in the incubation medium. Spontaneous and polymorphonuclear leukocyte-associated lysis tended to be lower in patients with acute cerebral ischemia (n=9, 24 hours, 9.5+/-1.8% and 12.9+/-2.2%) than in age- and sex-matched control subjects (n=8; 12.2+/-2.0% and 17.4+/-1.9%). In the presence of alpha(2)-antiplasmin, thrombolysis tended to be faster with elastase-digested plasminogen (miniplasminogen) than with native plasminogen. Purified polymorphonuclear leukocyte elastase itself had no thrombolytic effect. We conclude that the thrombolytic capacity of polymorphonuclear leukocytes from peripheral blood is small and slow and may have been overestimated in previous reports. Polymorphonuclear leukocyte thrombolytic activity may not be increased in acute cerebral ischemia. Miniplasminogen may be an interesting adjunct to plasminogen activators in acute stroke models.
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PMID:Thrombolytic properties of leukocytes from peripheral blood in healthy subjects and in patients with acute cerebral ischemia. 1070 31

Ischemic stroke results most commonly from cerebral arterial thrombosis. Antithrombotic agents can reduce the incidence of cerebral embolic events or the extent of tissue injury and neurological outcome. The antiplatelet agents aspirin, ticlopidine, and the combination of dipyridamole and aspirin are associated with a significant reduction in second focal cerebral ischemic events. Oral anticoagulants have a role to reduce the incidence of cardiogenic emboli in patients with mechanical cardiac valves or nonvalvular atrial fibrillation. Both antithrombotics are untested in the acute setting. The recombinant tissue plasminogen activator rt-PA has been shown to significantly increase the number of stroke patients with no or minimal deficit when treated within 3 hours of symptom onset. Additional studies of this and other plasminogen activators by both intravenous and intra-arterial delivery have highlighted limitations to this approach, but also support its role in acute intervention. The risk of intracerebral hemorrhage attends the use of all antithrombotic agents, most notably plasminogen activators. Strategies to decrease this risk are likely to add to beneficial outcome.
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PMID:Antithrombotic treatments in acute ischemic stroke. 1096 82

Ancrod is a purified fraction of venom from the Malayan pit viper, Calloselasma rhodostoma, currently under investigation for treatment of acute ischemic stroke. Treatment with ancrod leads to fibrinogen depletion. The present study investigated the mechanisms leading to the reduction of plasma fibrinogen concentration. Twelve healthy volunteers received an intravenous infusion of 0.17 U/kg body weight of ancrod for 6 hours. Blood samples were drawn and analyzed before and at various time points until 72 hours after start of infusion. Ancrod releases fibrinopeptide A from fibrinogen, leading to the formation of desAA-fibrin monomer. In addition, a considerable proportion of desA-profibrin is formed. Production of desA-profibrin is highest at low concentrations of ancrod, whereas desA-profibrin is rapidly converted to desAA-fibrin at higher concentrations of ancrod. Both desA-profibrin and desAA-fibrin monomers form fibrin complexes. A certain proportion of complexes carries exposed fibrin polymerization sites E(A), indicating that the terminal component of the protofibril is a desAA-fibrin monomer unit. Soluble fibrin complexes potentiate tissue-type plasminogen activator-induced plasminogen activation. Significant amounts of plasmin are formed when soluble fibrin in plasma reaches a threshold concentration, leading to the proteolytic degradation of fibrinogen and fibrin. In the present setting, high concentrations of soluble fibrin are detected after 1 hour of ancrod infusion, whereas a rise in fibrinogen and fibrin degradation products, and plasmin-alpha(2)-plasmin inhibitor complex levels is first detected after 2 hours of ancrod infusion. Ancrod treatment also results in the appearance of cross-inked fibrin degradation product D-dimer in plasma. (Blood. 2000;96:2793-2802)
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PMID:Analysis of fibrin formation and proteolysis during intravenous administration of ancrod. 1102 13

Tissue plasminogen (plgn) activator (tPA) modulates neuronal death in models of stroke, excitotoxicity, and oxidative stress. Amyloid-beta (Abeta) appears central to Alzheimer's disease and is neurotoxic to neurons in vitro. Here, we evaluate tPA effects on Abeta toxicity. We report that tPA alone had no effect on Abeta toxicity. However, in combination with plgn, tPA reduced Abeta toxicity in a robust fashion. Moreover, the combined tPA and plgn treatment markedly inhibited Abeta accumulation. The addition of phenylmethylsulfonyl fluoride, a serine protease inhibitor, to a sample of tPA, plgn, and Abeta resulted in a marked reduction of Abeta degradation. We interpret the actions of tPA and plgn within the context of the ability of plasmin to degrade Abeta.
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PMID:Tissue plasminogen activator requires plasminogen to modulate amyloid-beta neurotoxicity and deposition. 1103 7

Recent studies confirm and extend previous evidence that lipoprotein (Lp) plays a significant role in atherosclerosis and is one of the top five or six risk factors for cardiovascular disease. In Japanese patients, Lp levels and apo phenotypes are significant predictors for myocardial infarction. Lp levels are significantly higher in ischemic stroke patients than in controls. However, plasma concentrations of Lp are not predictive of ischemic cerebral infarction in either men or women. Serum Lp levels are significantly higher in patients with carotid plaques or measurable intima-media thickness than in controls without. Despite these associations, there is no significant relationship between Lp level and arterial endothelial function, smooth muscle response, or carotid wall thickness, even though other lipid risk factors like low-density lipoprotein cholesterol (LDL-C) and LDL-C/high-density lipoprotein cholesterol (HDL-C) ratio are correlated with abnormal arterial function and structure. There is new evidence that the association of Lp with extracellular matrix (ECM) secreted by arterial smooth muscle cells increases two- to threefold the subsequent specific binding of LDL. Alpha-defensins released from activated or senescent neutrophils stimulate the binding of Lp to ECM of endothelial cells. Several factors that affect the accumulation of Lp and oxidized LDL in the arterial intima have been identified. Several recent studies have provided new insights into the physiologic role that Lp might play in compromising fibrinolysis. The interaction of Lp with cells is clearly distinct from that with ECM and with fibrinogen; the regulation sites within Lp and plasminogen for these regulatory molecules are not identical. These recent advances bring us significantly closer to understanding how Lp exerts its atherogenic and thrombogenic properties.
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PMID:The role of lipoprotein[a] in atherosclerosis. 1112 50

The development of novel gene technologies in mice has provided an elegant tool to identify gene products that are causally linked to certain physiologic processes as well as the pathogenesis of numerous disorders. Using these techniques, three major proteolytic systems -- the plasminogen, the matrix metalloproteinase (MMP) and the coagulation systems -- have been shown to be involved in cardiovascular diseases, which still constitute the leading cause of death in Western societies. This overview summarizes the role of these proteolytic systems in angiogenesis, arterial stenosis, allograft transplant stenosis, vein graft stenosis, atherosclerosis, myocardial infarction, cardiac development and ischemic stroke and discusses possible therapeutic implications.
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PMID:The role of proteinases in angiogenesis, heart development, restenosis, atherosclerosis, myocardial ischemia, and stroke: insights from genetic studies. 1112 72

Childhood ischemic stroke, including arterial ischemic stroke (AIS) and sinovenous thrombosis (SVT), is relatively rare in children but can result in devastating morbidity and mortality. An understanding of the etiology of childhood stroke is important because strategies for primary and secondary prevention can be devised. Prothrombotic disorders may contribute to the etiology of childhood stroke, and include deficiencies of antithrombin, protein C, protein S, plasminogen, and presence of Factor V Leiden, Prothrombin gene G20210A, dysfibrinogenemia, antiphospholipid antibodies, hyperhomocysteinemia, and elevated lipoprotein (a). The overall incidence of prothrombotic disorders in childhood AIS is estimated to be 20% to 50% in most studies and, in childhood SVT, to be 33% to 99%. In addition, hyperlipidemia, polycythemia, iron deficiency anemia, and platelet disorders may result in a prothrombotic state associated with ischemic stroke. The etiologic contribution of these prothrombotic disorders to initial and recurrent stroke has not been clearly defined; however, additional risk factors are usually present in affected children. Given the prevalence of prothrombotic disorders in childhood stroke, and their likely causative role, children with stroke should be screened for prothrombotic disorders. Future prospective and multicenter studies will elucidate the contribution of specific prothrombotic disorders to initial and recurrent stroke, and optimal therapy.
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PMID:Prothrombotic disorders and ischemic stroke in children. 1120 19

The fibrinolytic system plays an important role in the physiological maintenance of blood flow and the dissolution of thrombi. Administration of fibrinolytic agents in indications such as myocardial infarction, pulmonary embolism, deep vein thrombosis or stroke, therefore, offers a rational means to dissolve pathological thrombi and restore vascular patency. The functional domains of the physiological tissue plasminogen activator (t-PA) provide fibrin specificity and serine protease activity for plasminogen cleavage and binding to liver receptors which gives the molecule a short half-life. In order to combat acute thromboembolic events such as myocardial infarction, the structure of the natural t-PA molecule was genetically modified to prolong its half-life, to increase its fibrin-specificity and to improve its resistance to plasminogen activator inhibitor. These features of TNK-t-PA allow bolus administration in emergency situations, early reperfusion of the blood vessel and a low rate of bleeding complications, thus improving the overall benefit to patients.
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PMID:Improving natural principles with genetic engineering: TNK-tissue plasminogen activator. 1145 85


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