scholarly journals Sex-Differences in the Impact of Metabolic Syndrome on Tissue Plasminogen Activator–Induced Recanalization

Stroke ◽  
2009 ◽  
Vol 40 (4) ◽  
Author(s):  
Georgios Tsivgoulis ◽  
Konstantinos Voumvourakis ◽  
Elefterios Stamboulis
Keyword(s):  
Metabolic Syndrome ◽  
Sex Differences ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Tissue Plasminogen ◽  
The Impact

scholarly journals The Impact of Loading Dose on Outcome in Stroke Patients Receiving Low-Dose Tissue Plasminogen Activator Thrombolytic Therapy

2020 ◽  
Vol Volume 14 ◽  
pp. 257-263 ◽  
Author(s):  
Yi-Sin Wong ◽  
Sheng-Feng Sung ◽  
Chi-Shun Wu ◽  
Yung-Chu Hsu ◽  
Yu-Hsiang Su ◽  
...  
Keyword(s):  
Thrombolytic Therapy ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Low Dose ◽  
Loading Dose ◽  
Stroke Patients ◽  
Tissue Plasminogen ◽  
The Impact

Regulation of primary hemostasis and vascular endothelial function by glyprolines in metabolic syndrome

2019 ◽  
Author(s):  
М.Е. Григорьева ◽  
Л.А. Ляпина ◽  
Т.Ю. Оберган
Keyword(s):  
Nitric Oxide ◽  
Metabolic Syndrome ◽  
Platelet Aggregation ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Structural Characteristics ◽  
Tissue Plasminogen ◽  
Anticoagulation System

Введение. Метаболический синдром (МС) сопровождается гиперлипемией, гиперкоагуляцией, дисфункцией эндотелия и др. В связи с этим не вызывает сомнений актуальность поиска новых средств комбинированного действия, восстанавливающих как жировой обмен, так и нормальную функцию эндотелия и сосудистотромбоцитарный гемостаз. Цель исследования: изучить в сравнительном аспекте влияние глипролинов ProGlyPro, ProArgPro, ArgProGlyPro и ProGlyProLeu на характеризующие эндотелиальную функцию и состояние сосудистотромбоцитарного гемостаза тканевой активатор плазминогена, уровень конечных метаболитов оксида азота и агрегацию тромбоцитов у крыс с МС. Материалы и методы. Для развития метаболических нарушений крысы получали высококалорийную диету (ВКД). Спустя 6 нед при продолжении ВКД животным интраназально вводили исследуемые пептиды в дозе 50 мкг/кг ежедневно в течение 7 сут. В плазме крови крыс через 20 ч и через 7 сут после последнего введения препаратов определяли показатели системы фибринолиза, АДФагрегацию тромбоцитов, конечные метаболиты оксида азота. Результаты. Развитие МС у крыс приводило к депрессии функции противосвертывающей системы и дисфункции эндотелия. Пролинсодержащие пептиды, применяемые в моделируемых условиях, вызывали активацию антитромбоцитарного звена противосвертывающей системы и эндотелиальной функции. Установлено, что исследуемые глипролины оказывали в кровотоке при их многократном применении выраженные в разной степени однонаправленные изменения в тромбоцитарном гемостазе. Максимальное снижение агрегации тромбоцитов выявлено для ProArgPro. Этот трипептид также в значительной степени активировал сосудистоэндотелиальную функцию путем усиленного выброса в кровоток маркеров тканевого активатора плазминогена и конечных метаболитов оксида азота. Заключение. Наиболее выраженное и устойчивое действие на гемостатическую и эндотелиальную функции в моделируемых условиях у глипролина ProArgPro может быть обусловлено структурными особенностями регуляторных пептидов, а именно, расположением аминокислот аргинина и пролина в непосредственной близости друг от друга. Introduction. Metabolic syndrome (MS) is accompanied by hyperlipemia, hypercoagulability, endothelial dysfunction. The search for new means of combined action, restoring fat metabolism and normal function of the endothelium and platelet hemostasis is relevant. Aim: to study the effect of ProGlyPro, ProArgPro, ArgProGlyPro and ProGlyPro Leu on tissue plasminogen activator, level of final nitric oxide metabolites and platelet aggregation in MS rats. Materials and methods. Rats received a highcalorie diet for the development of MS. After 6 weeks, the peptides were administered intranasally to animals at a dose 50 g/kg daily for 7 days. Parameters of fibrinolysis system, ADPplatelet aggregation, and final metabolites of nitric oxide were determined in rat blood plasma 20 hours and 7 days after the last drugs administration. Results. The development of MS in rats led to depression of anticoagulation system and endothelial dysfunction. Prolinecontaining peptides in simulated conditions caused activation of anticoagulation system and endothelial function. The studied peptides with their repeated use led in the bloodstream to unidirectional changes of varying degrees in platelet haemostasis after their multiple intranasal applications to animals. The maximum reduction in platelet aggregation was detected for ProArgPro. This tripeptide significantly increased the levels of final metabolites of nitric oxide and tissue plasminogen activator. Conclusion. The most pronounced and stable effect on hemostatic and endothelial functions in simulated conditions was identified for ProArgPro. Perhaps this effect is due to the structural characteristics of peptides, namely, the position of arginine in close proximity of proline.

Utilization of Intravenous Tissue Plasminogen Activator for Ischemic Stroke: Are There Sex Differences?

2009 ◽  
Vol 27 (3) ◽  
pp. 254-258 ◽  
Author(s):  
Norrina B. Allen ◽  
Daniela Myers ◽  
Emi Watanabe ◽  
Jackie Dostal ◽  
Danny Sama ◽  
...  
Keyword(s):  
Sex Differences ◽  
Ischemic Stroke ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Intravenous Tissue Plasminogen Activator ◽  
Tissue Plasminogen

scholarly journals Intravenous Tissue Plasminogen Activator in Combination With Mechanical Thrombectomy: Clot Migration, Intracranial Bleeding, and the Impact of “Drip and Ship” on Effectiveness and Outcomes

2020 ◽  
Vol 11 ◽  
Author(s):  
Adam Chang ◽  
Elham Beheshtian ◽  
Edward J. Llinas ◽  
Oluwatoyin R. Idowu ◽  
Elisabeth B. Marsh
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Mechanical Thrombectomy ◽  
Hemorrhagic Transformation ◽  
Anterior Circulation ◽  
Vessel Occlusion ◽  
Intravenous Tissue Plasminogen Activator ◽  
Tissue Plasminogen ◽  
The Impact ◽  
Iv Tpa

Purpose: Intravenous tissue plasminogen activator (tPA) is indicated prior to mechanical thrombectomy (MT) to treat large vessel occlusion (LVO). However, administration takes time, and rates of clot migration complicating successful retrieval and hemorrhagic transformation may be higher. Given time-to-effectiveness, the benefit of tPA may vary significantly based on whether administration occurs at a thrombectomy-capable center or transferring hospital.Methods: We prospectively evaluated 170 individuals with LVO involving the anterior circulation who underwent MT at our Comprehensive Stroke Center over a 3.5 year period. Two thirds (n = 114) of patients were admitted through our Emergency Department (ED). The other 33% were transferred from outside hospitals (OSH). Patients meeting criteria were bridged with IV tPA; the others were treated with MT alone. Clot migration, recanalization times, TICI scores, and hemorrhage rates were compared for those bridged vs. treated with MT alone, along with modified Rankin scores (mRS) at discharge and 90-day follow-up. Multivariable regression was used to determine the relationship between site of presentation and effect of tPA on outcomes.Results: Patients presenting to an OSH had longer mean discovery to puncture/recanalization times, but were actually more likely to receive IV tPA prior to MT (70 vs. 42%). The rate of clot migration was low (11%) and similar between groups, though slightly higher for those receiving IV tPA. There was no difference in symptomatic ICH rate after tPA. TICI scores were also not significantly different; however, more patients achieved TICI 2b or higher reperfusion (83 vs. 67%, p = 0.027) after tPA, and TICI 0 reperfusion was seen almost exclusively in patients who were not treated with tPA. Those bridged at an OSH required fewer passes before successful recanalization (2.4 vs. 1.6, p = 0.037). Overall, mean mRS scores on discharge and at 90 days were significantly better for those receiving IV tPA (3.9 vs. 4.6, 3.4 vs. 4.4 respectively, p ~ 0.01) and differences persisted when comparing only patients recanalized in under 6 h.Conclusion: Independent of site of presentation, IV tPA before MT appears to lead to better radiographic outcomes, without increased rates of clot migration or higher intracranial hemorrhage risk, and overall better functional outcomes.

scholarly journals Tissue plasminogen activator prevents white matter damage following stroke

2011 ◽  
Vol 208 (6) ◽  
pp. 1229-1242 ◽  
Author(s):  
Fernando Correa ◽  
Maxime Gauberti ◽  
Jérôme Parcq ◽  
Richard Macrez ◽  
Yannick Hommet ◽  
...  
Keyword(s):  
White Matter ◽  
Plasminogen Activator ◽  
Cell Fate ◽  
Tissue Plasminogen Activator ◽  
Mechanism Of Action ◽  
White Matter Lesions ◽  
Brain Diseases ◽  
Stroke Treatment ◽  
Tissue Plasminogen ◽  
The Impact

Tissue plasminogen activator (tPA) is the only available treatment for acute stroke. In addition to its vascular fibrinolytic action, tPA exerts various effects within the brain, ranging from synaptic plasticity to control of cell fate. To date, the influence of tPA in the ischemic brain has only been investigated on neuronal, microglial, and endothelial fate. We addressed the mechanism of action of tPA on oligodendrocyte (OL) survival and on the extent of white matter lesions in stroke. We also investigated the impact of aging on these processes. We observed that, in parallel to reduced levels of tPA in OLs, white matter gets more susceptible to ischemia in old mice. Interestingly, tPA protects murine and human OLs from apoptosis through an unexpected cytokine-like effect by the virtue of its epidermal growth factor–like domain. When injected into aged animals, tPA, although toxic to the gray matter, rescues white matter from ischemia independently of its proteolytic activity. These studies reveal a novel mechanism of action of tPA and unveil OL as a target cell for cytokine effects of tPA in brain diseases. They show overall that tPA protects white matter from stroke-induced lesions, an effect which may contribute to the global benefit of tPA-based stroke treatment.

scholarly journals Factors Affecting the Apparent Efficacy and Safety of Tissue Plasminogen Activator in Thrombotic Occlusion Models of Stroke: Systematic Review and Meta-Analysis

2010 ◽  
Vol 30 (12) ◽  
pp. 1905-1913 ◽  
Author(s):  
Emily S Sena ◽  
Catherine L Briscoe ◽  
David W Howells ◽  
Geoffrey A Donnan ◽  
Peter AG Sandercock ◽  
...  
Keyword(s):  
Systematic Review ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Odds Ratio ◽  
Infarct Volume ◽  
Meta Analysis ◽  
Efficacy And Safety ◽  
Thrombotic Occlusion ◽  
Tissue Plasminogen ◽  
The Impact

Thrombolysis with recombinant tissue plasminogen activator (rtPA) improves outcome in animal models of stroke and in clinical trial, but is associated with increased intracranial hemorrhage. Here, we explore the impact of biologic and experimental design factors on efficacy and bleeding. We conducted a systematic review of studies describing the effect of tPA in thrombotic occlusion models of ischemic stroke followed by random effects meta-analysis, meta-regression, and trim and fill. We identified 202, 66, 128, and 54 comparisons reporting infarct volume, neurobehavioral score, hemorrhage, and mortality, respectively. The rtPA reduced infarct volume by 25.2% (95% confidence interval=21.8 to 28.6, 3388 animals), improved neurobehavioral score by 18.0% (12.6% to 23.3%, n=1243), increased the risk of hemorrhage (odds ratio=1.71, 1.42 to 2.07, n=2833) and had no significant effect on mortality (odds ratio=0.82, 0.62 to 1.08, n=1274). There was an absolute reduction in efficacy of 1.1% (0.7% to 1.4%) for every 10 minutes delay to treatment. Cumulative meta-analysis showed that the estimate of efficacy fell as more data became available. Publication bias inflated efficacy by 5.1% (infarct volume) and 8.1% (neurobehavioral score). This data set was large enough to be adequately powered to estimate with precision the impact of biologic and experimental factors on the efficacy and safety of rtPA.

scholarly journals The effect of glyproline peptides on levels of nitric oxide metabolites and tissue plasminogen activator activity in healthy rats and rats with metabolic syndrome

2020 ◽  
pp. 88-94
Author(s):  
Т.Ю. Оберган ◽  
М.Е. Григорьева ◽  
Л.А. Ляпина ◽  
Т.А. Шубина ◽  
Н.Ф. Мясоедов ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Metabolic Syndrome ◽  
Endothelial Function ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Tissue Plasminogen ◽  
Male Wistar Rats ◽  
Nitric Oxide Metabolites ◽  
Nitrate And Nitrite ◽  
Academy Of Sciences

Введение. Короткие регуляторные пролинсодержащие пептиды могут оказывать противосвертывающие эффекты в организме и проявлять защитное действие при тромбозах. Цель исследования - выявление косвенных эффектов пептидов глипролинового ряда Pro-Gly-Pro (PGP) и Arg-Glu-Arg-Pro-Gly-Pro (RERPGP) на функцию эндотелия сосудов и состояние системы фибринолиза в норме и при нарушении липидного обмена. Методика. Пептиды были синтезированы в институте молекулярной генетики РАН. В экспериментах использовано 60 лабораторных белых крыс-самцов линии Wistar. Проведено 2 серии экспериментов - на здоровых крысах и животных с экспериментально воспроизведенным метаболическим синдромом (МС). Пептиды вводили интраназально в течение 7 сут через каждые 24 ч (100 мкг/кг) ежедневно. Анализ крови осуществляли через 20 и 168 ч после завершающего введения пептидов. Определяли уровни метаболитов оксида азота (NO) и активности тканевого активатора плазминогена (ТАП). Результаты. Выявлены различия в действии PGP и RERPGP на исследуемые параметры у здоровых животных. В плазме крови крыс через 20 ч после семикратного введения пептида PGP установлено значительное повышение активности ТАП и метаболитов NO, которое сохранялось на протяжении 168 ч эксперимента, в то время как под влиянием RERPGP отмечалось повышение только уровня нитратов и нитритов через 168 ч после его применения. Пептид PGP также оказывал выраженные эффекты на функцию эндотелия организма и при развитии МС. Активность ТАП значительно и статистически значимо увеличивалась через 20 ч после семикратного введения пептида, эти изменения наблюдались также спустя 168 ч после применения PGP. Эти величины практически соответствовали значениям ТАП у здоровых крыс. Уровень метаболитов NО также значимо повышался при воздействии PGP на фоне МС. Сделано предположение о возможных механизмах действия пептидов на сосудистый эндотелий. Заключение. Пептиды глипролинового ряда оказывали стимулирующее влияние на функцию эндотелия в организме как в норме, так и при патологии, повышая активность тканевого активатора плазминогена и концентрацию метаболитов оксида азота. Short regulatory proline-containing peptides can exert an anticoagulation effect and be protective in thrombosis. The aim of this study was to identify indirect effects of glyproline peptides Pro-Gly-Pro (PGP) и Arg-Glu-Arg-Pro-Gly-Pro (RERPGP) on vascular endothelial function and the fibrinolytic system in normal and impaired lipid metabolism. Methods. Peptides were synthesized at the Institute of Molecular Genetics, Russian Academy of Sciences. Experiments were performed on 60 male Wistar rats divided into healthy animals and animals with experimental metabolic syndrome (MS). Peptides (100 μg/kg) were administered intranasally, once a day for 7 days. Blood tests were performed 20 h and 168 h after the last administration of the peptides. Concentrations of nitric oxide (NO) metabolites (sum plasma concentration of nitrate and nitrite) and the activity of tissue plasminogen activator (TAP) were measured. Results. The effects of PGP and RERPGP on the endothelial function in healthy animals were different. Significant increases in both TAP activity and NO metabolite concentration were found in plasma 20 h after 7 PGP administrations, which persisted throughout 168 h of the experiment. Only an increase in nitrate/nitrite was observed at 168 h after the RERPGP administration. PGP also exerted pronounced effects on the endothelial function, including in MS. TAP activity was significantly increased at 20 h after 7 administrations of the peptide, and this effect remained at 168 h after the PGP administration. These values were practically similar to the TAP values in healthy rats. Concentrations of NO metabolites were also significantly increased after the PGP exposure of MS rats. Possible mechanisms for the peptide activation of vascular endothelium are discussed. Conclusion. Glyproline peptides had a stimulatory effect on the endothelial function both in normal and pathological conditions by increasing the TAP activity and the concentration of NO metabolites.

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