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1.
Clinical studies on rt-PA (recombinant tissue-type plasminogen activator) treatment of stroke showed a favorable outcome. However, there are reports of harmful effects of t-PA via the potentiation of excitotoxic injury. We used combined X-ray angiography and MRI imaging to study the balance between the beneficial effect of reperfusion and secondary detrimental effects of rt-PA. Therefore, rats (n=15) were assigned to three groups according to recanalization or lack thereof of the middle cerebral artery (MCA) and rt-PA or saline treatment in an embolic stroke model. Diffusion and perfusion MRI showed that animals had significantly improved perfusion values and final infarct size when recanalization was successful. However, final infarct volumes at 6 h post stroke onset were greater in the rt-PA group compared to controls at comparable perfusion values when the MCA did not recanalize after treatment (67.4+/-5.4 versus 47.7+/-17.9% of ipsilateral hemisphere, P=0.042). Our results demonstrate that the combination of angiography and MR-imaging is useful to further evaluate rt-PA treatment of thromboembolic stroke.  相似文献   

2.
Thrombolysis of cerebral clot embolism in rat: effect of treatment delay   总被引:3,自引:0,他引:3  
Rats submitted to focal cerebral ischemia by middle cerebral artery clot embolism were treated with recombinant tissue plasminogen activator (rt-PA) at increasing delays (1.5, 3 and 4.5 h) after the onset of ischemia. Treatment efficacy was evaluated by NMR imaging of the apparent diffusion coefficient of water (ADC). In untreated animals the size of the ADC-detectable lesion gradually increased after clot embolism, expanding over 8 h to 174 +/- 17% of the volume visible at 30 min. Thrombolysis initiated 1.5 h after embolism did not reverse the ischemic lesion but reduced its growth to 113 +/- 19% (p < 0.05). Lesion size increased to 135 +/- 14% after 3 h (NS) and to 214 +/- 35% after 4.5 h delay (NS). Thrombolysis with rt-PA attenuates infarct expansion but does not reverse ischemic injury.  相似文献   

3.
The effect of thrombolytic therapy on metabolic changes was studied in rats submitted to thromboembolic stroke. Reperfusion was initiated at three different time points, 1.5, 3, and 4.5 hours after embolism (n = 3 each), by injection of recombinant tissue-type plasminogen activator (rt-PA). Recovery was observed during 5 hours of reperfusion using perfusion-weighted images and a two-dimensional 1H magnetic resonance spectroscopic imaging (MRSI) technique. Temporal evolution of the cerebral metabolites lactate and N-acetyl-aspartate (NAA) was determined. To analyze the chances of metabolic tissue recovery, the outcome of treatment, defined by a reversal of lactate concentration, was compared with the lactate intensity before treatment. In untreated animals (n = 4), clot embolism resulted in a drop of perfusion signal intensity in the occluded hemisphere followed by an increase of lactate concentration and a decrease of NAA that persisted throughout the observation period. Thrombolysis partially restored blood flow, but the mean lactate concentration decreased only slightly after successful lysis in animals treated 1.5 hours after embolism. If treatment was initiated later, no decline of lactate level was observed. Five hours after initiation of thrombolysis, the average tissue lactate amounted to 95 +/- 6, 111 +/- 17, and 139 +/- 60% of the early ischemic value (40 minutes after embolization) if treatment began 1.5, 3, and 4.5 hours after embolism, respectively. The NAA level declined slightly but never showed a recovery after rt-PA treatment. In individual pixels, the probability of metabolic tissue recovery clearly declined with increasing lactate concentration before thrombolysis. Interestingly, this probability was independent of treatment delay, but the number of pixels with low lactate declined with increasing ischemia time. Potential clinical applications of MRSI include monitoring of therapeutic intervention as well as support for prognosis of outcome after rt-PA treatment.  相似文献   

4.
A rapid and complete recanalization of the occluded artery is the ideal goal when intravenous (IV) recombinant tissue plasminogen activator (rt-PA) is administrated to patients with acute ischemic stroke, i.e., limiting the ongoing ischemia to achieve a better outcome. We explored the effect of complete versus partial recanalization of the occluded intracranial artery after IV thrombolysis on the infarct growth and evaluated the functional impact. Using diffusion-weighted (DWI) volumetric measurements before rt-PA administration (DWI(1)) and 24?h later (DWI(2)), we calculated the infarct growth in 36 consecutive patients with ischemic stroke treated with IV rt-PA, with the formula DWI(2)/DWI(1). Recanalization of the affected artery was assessed by transcranial Doppler (TCD) and magnetic resonance angiography (MRA) within 24?h of stroke onset. Three patients were eliminated from the analysis; 33?patients were fully analyzed (men: n?=?23; mean (SD) age: 72.4?±?16?years; time from stroke onset to rt-PA: 179?±?54?min; mean NIHSS score at admission: 17). Patients achieving full recanalization by TCD had a smaller infarct growth, compared to those who had a partial or persistent occlusion after thrombolysis: 1.86 versus 2.91 (P?=?0.017). This difference was not significant using MRA criteria: 2.01 versus 2.69 (P?=?0.193). In the regression analysis, complete recanalization by TCD was an independent predictor of infarct growth (P?=?0.045). Thus, complete recanalization measured by TCD within 24?h of IV thrombolysis was independently associated with smaller infarct growth.  相似文献   

5.
INTRODUCTION: Ischemic stroke causes substantial death and disability. Currently, recombinant tissue plasminogen activator (rt-PA) is the only FDA approved therapy. However, there are dangerous side effects and therapy must start within 3 h of onset. Therefore, there is interest in adjunctive therapies such as ultrasound enhanced thrombolysis (UET) and hypothermia. Recently, transcranial ultrasound during rt-PA therapy was shown to improve vessel recanalization. Also hypothermia (32-34 degrees C) was shown to be safe and possibly improve outcome. This suggests combining UET and hypothermia to treat ischemic stroke. Little is known about the effects of hypothermia on UET, and in-vitro rt-PA efficacy is reduced for T<37 degrees C. Here, the effects of hypothermia on UET in in-vitro human clot are presented. It is hypothesized that UET efficacy at 33 degrees C is less than at 37 degrees C. MATERIALS AND METHODS: Whole blood was drawn from volunteers. Clots were made, incubated at 37 degrees C and aged for 2 days for maximal lytic resistance. Clots were exposed to human fresh-frozen plasma (control), hFFP and rt-PA ([rt-PA]=3.2 microg/ml), hFFP and 120 kHz ultrasound (US), and hFFP, rt-PA and ultrasound (UET) at 33 degrees C and 37 degrees C. Clot percent mass loss (Deltam) was measured to determine thrombolytic efficacy. Data were analyzed using mixed-model analysis of variance. RESULTS AND CONCLUSIONS: US and rt-PA independently increased Deltam (3.5+/-1.0% and 5.1+/-0.9% respectively; p<0.01) over control. UET increased Deltam an additional 8.1+/-1.3% (p=0.026) The effect of temperature on Deltam (-1.6+/-0.7%) was not significant (p=0.09). Hypothermia did not reduce UET efficacy in this in-vitro model.  相似文献   

6.
Uric acid is a natural antioxidant that protects the brain in a model of transient focal ischemia in rats. Here we sought to investigate whether uric acid was protective in a model of thromboembolic brain ischemia in rats, and whether the global benefit of recombinant tissue plasminogen activator (rt-PA) was improved by the combined treatment. Adult male Sprague-Dawley rats underwent either ischemia by thromboembolic middle cerebral artery occlusion (MCAO) or sham operation. Uric acid (16 mg/kg) was injected intravenously (i.v.). 20 mins after MCAO, whereas rt-PA (10 mg/kg) was administered i.v. at 3 h. A group of rats received the combined treatment. Rats underwent two neurologic examinations (30 mins and 24 h after MCAO). At 24 h, infarct volume was measured and brain neutrophil infiltration and protein tyrosine nitration were assessed. Treatment with either uric acid or rt-PA reduced infarct volume versus controls (P<0.05). The protective effect against brain ischemia was greater after cotreatment of uric acid with rt-PA (P<0.001), which added further benefit to rt-PA alone (P<0.05). The neurologic score worsened during the first 24 h in treatment controls, whereas it improved in rats receiving uric acid and/or rt-PA. Uric acid strongly reduced ischemia-induced tyrosine nitration, but it was more effective alone than combined with rt-PA, suggesting that reperfusion enhances nitrotyrosine formation. All treatments reduced postischemic brain neutrophil infiltration. These results show that uric acid administered early after thromboembolic stroke is neuroprotective in the rat brain, as it reduces infarct volume, ameliorates the neurologic function, attenuates the inflammatory response, and extends the benefits of rt-PA.  相似文献   

7.
目的:探讨发病6h内急性脑梗死给予重组组织型纤溶酶原激活物(rt-PA)溶栓治疗的疗效及并发症,并分析预后相关因素。方法:共收集本院2001-2005年70例溶栓治疗的急性脑梗死病例,其中52例静脉溶栓,18例动脉溶栓,分析比较两组病例溶栓前后及3个月随访的ESS评分及Barthel指数结果;同时分析与预后相关的因素。结果:静脉和动脉溶栓组溶栓前及溶栓30min后ESS评分及Barthel指数迅速增加,溶栓前后分值有显著差异。1个月内颅内出血率为5.77%(静脉组)和16.67%(动脉组)。3个月时ESS评分及Barthel指数较溶栓后30min的评分有显著改善。结论:6h内动脉、静脉溶栓治疗均安全有效。  相似文献   

8.
Magnetic resonance angiography (MRA) was performed in a thromboembolic stroke model of the rat to characterize intracranial vessel occlusion patterns and to test its predictive power for tissue recovery after recombinant tissue plasminogen activator (rt-PA) treatment. After rt-PA-treated selective middle cerebral artery (MCA) occlusion, full recanalization was observed in two of three animals, whereas additional occlusion of the circle of Willis (CW) resulted in full vascular flow restitution in only one of six rats. Tissue reperfusion markedly lagged the onset of treatment, and the delay correlated with the pattern of vessel occlusion (20 to 23 minutes for selective MCA occlusion vs. 71 to 79 minutes for combined MCA/CW occlusion). In lateral cortex and striatum the apparent diffusion coefficient decreased to 78 +/- 15% of control after embolization, recovered to 80% to 85% after rt-PA treatment of selective MCA occlusion, but further declined to 66% to 69% after combined MCA/CW occlusion. Correspondingly, T2 relaxation time increased to 107% to 118% of control after selective MCA occlusion and to 112% to 124% after combined MCA/CW occlusion in these regions. The present investigation shows that MRA provides valuable information on the severity of thromboembolic stroke and has the power to predict, before the initiation of treatment, the functional tissue outcome after rt-PA-induced thrombolysis.  相似文献   

9.
目的探讨重组组织型纤溶酶原激活剂(rt-PA)静脉溶栓治疗急性脑梗死的临床效果及安全性。方法选择发病在4.5h内,平均2.86±0.8h内急性脑梗死患者73例,分为两组,溶栓组50例患者给予rt-PA 0.9mg·kg-1·d-1静脉溶栓,常规治疗组23例患者采用抗血小板聚集药物等治疗,比较溶栓和常规治疗后24h、7d及14d美国国立卫生研究院卒中量表(NIHSS)评分并记录不良反应。结果溶栓组治疗后24h、7d及14d时,NIHSS评分较溶栓前及对照组均明显减少,差异有统计学意义(P<0.05);溶栓后头颅MRI/CT及临床表现提示未出现症状性脑出血。结论 rt-PA静脉溶栓治疗发病4.5h内脑梗死是安全有效的。  相似文献   

10.
Effect of hypothermia on cerebral infarcts was studied in rats embolized in the right carotid territory. Thirty-four served as normothermic controls receiving saline infusion only. In 16 rats hypothermia of 32°C was induced by cooling with a fan, followed by embolization. The rats were kept hypothermic for the following 3 h before body temperature was raised to 37°C. In 26 rats, treatment with human recombinant tissue plasminogen activator (20 mg/kg i.v. during 45 min), started 2 h after embolization. Finally, 14 rats were treated similarly with hypothermia for 3 h followed by additional rt-PA treatment starting after 2 h. Thrombolytic therapy reduced median infarct volume from 19.5% of affected hemisphere among controls to 4.6% (p = 0.006) in the treated group. Three hours of hypothermia reduced infarct volume to 1.6% (p = 0.0007). Additional rt-PA could not demonstrate further improvement in this experimental setting.  相似文献   

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