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1.
Inhibition of carboxypeptidase U (TAFIa) activity improves rt-PA induced thrombolysis in a dog model of coronary artery thrombosis 总被引：3，自引：0，他引：3
The objective of this study was to test the hypothesis if thrombolysis induced by recombinant tissue-type plasminogen activator, (rt-PA) could be facilitated by inhibiting carboxypeptidase U (CPU, active Thrombin Activatable Fibrinolysis Inhibitor, TAFIa) activity. The efficacy of rt-PA alone, or in combination with the carboxypeptidase inhibitor MERGETPA, was compared in a dog model of coronary artery thrombosis. Twenty dogs were randomised in two groups, one received rt-PA, 1 mg kg−1, as intravenous infusion over 20 min starting 30 min after thrombus formation, and the other group received rt-PA, 1 mg kg−1, as group one with the addition of MERGEPTA 5 mg kg−1 starting 25 min prior to coronary artery occlusion and followed by infusion of 5 mg kg−1 h−1 until the end of experiment. Efficacy was assessed by determination of time to lysis, duration of patency and blood flow during patency. Both groups had similar baseline characteristics with respect to haemodynamic parameters, i.e., heart rate, blood pressure and coronary artery blood flow. Coadministration of rt-PA and MERGETPA resulted in significant decrease in time to lysis (15±1.5 min vs. 20±1.7 min, p=0.03), increased patency time (87±16 min vs. 46±12 min, p=0.047) and increased coronary blood flow during patency (1131 mL h−1 vs. 405 mL h−1, p=0.015), compared to rt-PA alone. These results indicate that an inhibitor of CPU activity may have a beneficial effect in patients undergoing thrombolytic therapy by attaining shorter time to reperfusion and improved coronary patency. 相似文献
2.
Combination therapy of moderate hypothermia and thrombolysis in experimental thromboembolic stroke--an MRI study 总被引：3，自引：0，他引：3
Kollmar R Henninger N Bardutzky J Schellinger PD Schäbitz WR Schwab S 《Experimental neurology》2004,190(1):204-212
Thrombolysis (T) is limited by reperfusion-associated injury and the short therapeutic window after stroke onset. The present study investigates whether hypothermia alone or in combination with thrombolysis has beneficial effects after experimental thromboembolic stroke. Wistar rats (n = 60) were subjected to thromboembolic occlusion (TE) of the middle cerebral artery (MCA). Thrombolysis (T) was performed with intravenous recombinant tissue-plasminogen activator (rt-PA) 1 h (early T) or 3 h (late T) after TE. Hypothermia (Hy) was applied for 4 h at 33 degrees C started 1 h after TE. Experimental groups included control (C), early thrombolysis (ET), late thrombolysis (LT), hypothermia (Hy), early thrombolysis plus hypothermia (ET+Hy), and late thrombolysis plus hypothermia (LT+Hy). Animals were investigated by MRI and silver infarct staining (SIS) to assess the cerebral infarct size. All animals of group Hy survived, in contrast to 40% in group C (P < 0.05). ET+HY and LT+Hy showed a trend towards better survival as compared to ET and LT alone. PWI parameters were not significantly different between ET versus ET+HY and LT versus LT+Hy, but rt-PA administration led to improved cerebral perfusion in MRI. Significant differences in infarct volumes (T2/SIS) were found after 24 h in all treatment groups versus the control group (P < 0.05). The lesion volume calculated from T2 was significantly smaller in ET (16% +/- 5%), ET+Hy (10 +/- 4%), and LT+Hy (20% +/- 9%) after 5.5 h (10.8% +/- 4.8%) versus C (42% +/- 15%), (P < 0.05). These data indicate that hypothermia improves survival and decreases infarct volume. However, there were no significant differences between the use of rt-PA alone or in combination with hypothermia. Further studies are needed to confirm these effects, also several days after stroke onset. 相似文献
3.
Ding G Jiang Q Zhang L Zhang Z Knight RA Soltanian-Zadeh H Lu M Ewing JR Li Q Whitton PA Chopp M 《Journal of the neurological sciences》2004,223(2):135-143
To increase the sensitivity of MRI parameters to detect tissue damage of ischemic stroke, an unsupervised analysis method, Iterative Self-Organizing Data Analysis Technique Algorithm (ISODATA), was applied to analyze the temporal evolution of ischemic damage in a focal embolic cerebral ischemia model in rat with and without recombinant tissue plasminogen activator (rt-PA) treatment. Male Wistar rats subjected to embolic stroke were investigated using a 7-T MRI system. Rats were randomized into control (n=9) and treated (n=9) groups. The treated rats received rt-PA via a femoral vein at 4 h after onset of embolic ischemia. ISODATA analysis employed parametric maps or weighted images (T1, T2, and diffusion). ISODATA results with parametric maps are superior to ISODATA with weighted images, and both of them were highly correlated with the infarction size measured from the corresponding histological section. At 24 h after embolic stroke, the average map ISODATA lesion sizes were 37.7+/-7.0 and 39.2+/-5.6 mm2 for the treated and the control group, respectively. Average histological infarction areas were 37.9+/-7.4 mm2 for treated rats and 39.4+/-6.1 mm2 for controls. The R2 values of the linear correlation between map ISODATA and histological data were 0.98 and 0.96 for treated and control rats, respectively. Both histological and map ISODATA data suggest that there is no significant difference in infarction area between non-treated and rt-PA-treated rats when treatment was administered 4 h after the onset of embolic stroke. The ISODATA lesion size analysis was also sensitive to changes of lesion size during acute and subacute stages of stroke. Our data demonstrate that the multiparameter map ISODATA approach provides a more sensitive quantitation of the ischemic lesion at all time points than image ISODATA and single MRI parametric analysis using T1, T2 or ADCw. 相似文献
4.
Despite the beneficial effect of systemic fibrinolysis in treatment within 3 hours from ischemic stroke onset, the unpredicted occurrence of intracerebral hemorrhage remains a risk from such therapy. Few data exist defining patients at risk for this outcome. We report clinical and neuropathological data on a patient fulfilling NINDS rt-PA study and ECASS-2 inclusion criteria with an acute stroke due to high-grade carotid artery stenosis and preceded by amaurosis fugax. He died from an intracerebral hemorrhage after systemic fibrinolysis. The fatal outcome adds support to recommendations that rapid Doppler-sonographic evaluation of the extra- and intracranial vascular status be undertaken before systemic rt-PA is implemented in acute ischemic stroke. 相似文献
5.
急性脑梗死动静脉联合与单纯静脉溶栓治疗的疗效观察 总被引：8，自引：2，他引：6
目的观察急性脑梗死动静脉联合(IA/IV)与单纯静脉(IV)重组组织型纤溶酶原激活物(rtPA)溶栓治疗的临床疗效。方法对20例急性脑梗死患者分别进行IA/IV(10例)与IV(10例)溶栓治疗,治疗前后分别进行欧洲卒中量表评分(ESS)和Barthel指数(BI)评分,观察其疗效及不良反应。结果IA/IV组患者闭塞段血管均有效再通,其中8例完全再通,2例部分再通;ESS及BI评分均明显高于IV组(均P<0.01),临床总有效率IA/IV组为90%,明显优于IV组的30%(P<0.05)。结论IA/IV溶栓治疗急性脑梗死是一种安全、有效的治疗方法,效果优于IV溶栓治疗。 相似文献
6.
INTRODUCTION: After the 2002 European agreement on the use of rt-PA for fibrinolysis within less than 3 hours after ischemic stroke, we designed a specific patient management scheme for patients referred to our center. METHODS: We report the activity of the "stroke emergency" pathway in the Purpan Hospital (Toulouse) for 4 years. We wanted to evaluate our daily practice and to confirm that the results obtained in the randomized clinical trials with rt-PA can be reproduced in routine practice. RESULTS: Among all stroke patients treated in the Neurology Department, 10.2 per cent were managed via this new pathway, in order to receive a fibrinolytic treatment. Amongst these, 25.6 per cent were treated with rt-PA (2.6 per cent of all ischemic and hemorrhagic strokes, with an average NIHSS score of 15.8 at admission [5; 25]. In 90 per cent of the cases, potential patients for thrombolysis were selected by CT-scan. Time from onset to treatment averaged 2 h 25 min, whilst door-to-treatment time averaged 40 minutes. Two patients (3 percent) showed a symptomatic intra-cerebral hemorrhage. Death rate was 18.8 per cent. After 3 months, 53.5 per cent of patients were regarded as functionally "independent" (Rankin scale<3). CONCLUSION: These results in our unit confirm the feasibility, reproducibility, efficacy and safety of the rt-PA fibrinolytic treatment for ischemic stroke of less than 3 hours. A "Stroke emergency" pathway appears to be a helpful option to treat as many patients as possible with the shortest possible lead times. 相似文献
7.
Zhu Zhang Zhen-guo Zhai Li-rong Liang Fang-fang Liu Yuan-hua Yang Chen Wang 《Thrombosis research》2014
Background and Objective
According to US Food and Drugs Administration (FDA), 2 hour recombinant tissue plasminogen activator (rt-PA) 100 mg infusion is recommended for eligible patients with acute pulmonary embolism (PE). However,there exists evidence implying that a lower dosage of rt-PA can be equally effective but potentially safer compared with rt-PA 100 mg regimen. The aim of this systematic review and meta-analysis is to assess the efficacy and safety of low dose rt-PA in the treatment of acute PE.Material and Method
We searched Pubmed, EMBASE, the Cochrane library and CBM Literature Database for randomized controlled trials (RCT) focusing on low dose rt-PA for acute PE. Outcomes were described in terms of changes of image tests and echocardiography, major bleeding events, all-cause death, and recurrence of PE.Results
Five studies (440 patients) were included, three of which compared low dose rt-PA (0.6 mg/kg, maximum 50 mg or 50 mg infusion 2 h) with standard dose (100 mg infusion 2 h). There were more major bleeding events in standard dose rt-PA group than in low dose group (OR 0.33, 95%CI 0.12-0.91;P = 0.94,I2 = 0%), while there were no statistical differences in recurrent PE or all cause mortality between these two groups. Two studies compared low dose (0.6 mg/kg, maximum 50 mg/2 min bolus or 10 mg bolus, ≤ 40 mg/2 h) with heparin. There was no significant difference in major bleeding events (OR 0.73, 95% CI 0.14-3.98;P = 0.72), recurrent PE or all cause mortality. No dose-related heterogeneity was found for all the included studies.Conclusions
The results of this meta-analysis were hypothesis-generating. Based on the limited data, our systematic review suggested that low dose rt-PA had similar efficacy but was safer than standard dose of rt-PA. In addition, compared with heparin, low dose rt-PA didn’t increase the risk of major bleeding for eligible PE patients. 相似文献8.
Nina Bizjak Franci Bajd Jernej Vidmar Aleš Blinc Maja Pohar Perme Victor J. Marder Valery Novokhatny Igor Serša 《Thrombosis research》2014
Introduction
Plasmin is a direct-acting thrombolytic agent with a favorable safety profile upon intra-arterial delivery in pre-clinical and phase I studies. However, the thrombolytic efficacy of plasmin, relative to that of rt-PA, remains to be established. We have compared the dynamics of clot lysis with plasmin or rt-PA in an in vitro perfusion system, in which thrombolytic agent is administered locally, allowed to induce lysis for short intervals, then washed with plasma in a re-circulation circuit.Materials and Methods
Whole blood human clots were prepared in observation chambers, exposed to plasmin or rt-PA at equimolar concentrations (1.2/1.0, 1.8/1.5 and 2.4/2.0 mg/ml) for measured intervals of time, followed by perfusion with human plasma. Clot size was monitored by digital analysis of sequential photographs obtained through an optical microscope.Results
Plasma perfusion after incubation with thrombolytic agent rapidly removed superficial clot fragments. This initial decrease in clot size was greater with plasmin than with rt-PA when tested at the highest concentrations of agent (0.63 ± 0.11 vs. 0.30 ± 0.11, p = 0.001 for clots with non-cross-linked fibrin and 0.53 ± 0.15 vs. 0.14 ± 0.15, p = 0.02, for clots with cross-linked-fibrin). Subsequent clot lysis during plasma flow was greater after prior incubation with rt-PA. Longer incubation times of plasmin resulted in larger portions of the clot being washed free. Repeated plasmin incubations and plasma perfusions of a clot successfully induced stepwise reductions in clot size.Conclusions
Initial clot lysis is greater with direct exposure using plasmin than rt-PA. During washout and circulation with plasma, rt-PA induced continued clot lysis, while plasmin lysis was curtailed, presumably because of plasmin inhibition. 相似文献9.
Background
The role of thrombolytic therapy for the initial treatment of hemodynamically stable patients experiencing an acute pulmonary embolism remains controversial.Methods and Results
We performed a meta-analysis of randomized trials comparing between administration of recombinant tissue plasminogen activator (rt-PA) and heparin in hemodynamically stable patients experiencing an acute pulmonary embolism. Seven trials, involving 594 patients, were included in this meta-analysis. Compared with heparin, rt-PA was associated with a non-significant reduction in death (2.75% versus 3.96%; RR 0.69, 95% CI 0.31-1.52, P for heterogeneity = 0.520) and recurrent pulmonary embolism (2.13% versus 3.34%; RR 0.70, 95% CI 0.28-1.73), and a non-significant increase in major bleeding (5.15% versus 4.29%; RR 1.06, 95% CI 0.520-2.150). Similar results were found based on a subgroup analysis of patients displaying echocardiographic evidence of right ventricular dysfunction (RVD). In contrast, rt-PA treatment was associated with a significant reduction in escalation of care in trials that also enrolled patients displaying RVD compared with heparin treatment (6.56% versus 19.7%; RR 0.34, 95% CI 0.20-0.65).Conclusion
The currently available data provide no evidence for a benefit of administration of rt-PA compared with heparin for the initial treatment of hemodynamically stable patients experiencing an acute pulmonary embolism. However, rt-PA is partially beneficial specifically among patients displaying RVD. 相似文献10.