阿加曲班治疗急性缺血性脑卒中的临床研究

目的观察阿加曲班治疗急性缺血性脑卒中的临床疗效及安全性。方法采用多中心、随机、开放性临床研究。随机选择发病48 h内的急性缺血性脑卒中患者132例,静脉输入阿加曲班,治疗7 d后观察美国国立卫生研究院卒中量表评分和改良Rankin量表及实验室检查和不良事件发生率。结果与治疗前比较,治疗后患者美国国立卫生研究院卒中量表评分明显降低、改良Rankin量表评分≤2分所占比例明显增高,差异有统计学意义(P0.05)。试验过程中未发生出血性脑卒中和脑出血等严重不良事件。结论阿加曲班可以改善急性缺血性脑卒中患者的预后及生活质量,具有较高的安全性。     

急性缺血性脑卒中溶栓治疗

<正>在过去的20年里,全球的年龄标化脑卒中病死率有所下降,但每年发生脑卒中的患者、脑卒中相关死亡和脑卒中的全球总负担的绝对数量巨大,而且仍在增加。脑卒中已成为我国城市和农村人口第一位致残和死亡原因,其中缺血性脑卒中占70%。在目前全球各国制定的指南中,静脉注射重组组织型纤溶酶原激活剂(rt-PA)标准剂量0.9mg/kg的治疗被推荐为缺血性脑卒中急性期的标准治疗方案。1静脉溶栓治疗的现状     

治疗急性缺血性卒中阿加曲班可增加rtPA疗效

美国得克萨斯休斯顿大学医学院Grotta等报道，阿加曲班与重组组织纤溶酶原激活物（rtPA）联用治疗急性缺血性卒中较安全，且增加脑动脉的再通率。rtPA静脉溶栓治疗急性缺血性卒中的益处是因为rtPA可使凝血块溶解，动脉再通。阿加曲班是直接凝血酶抑制剂，动物卒中模型实验证明，阿加曲班可安全地增加rtPA治疗缺血性卒中的疗效。     

急性缺血性脑卒中血管再通治疗的回顾与展望

<正>急性缺血性脑卒中(acute ischemic stroke,AIS)的预后与颅内闭塞血管能否及时再通密切相关。近年来,随着医药科技的发展,致力于提高AIS治疗效果的血管内介入治疗研究,从静脉溶栓、动脉溶栓、动脉及静脉联合溶栓、血管腔内成形术、支架成形术、机械碎栓到机械取栓,颅内大血管的再通率显著提高~([1-3])。特别是血管内机械取栓术,已成为治疗AIS的新方法~([4-5])。血管内机械取栓术能显著提高大血管闭塞的再通率,取得了良好的临床效果。     

替罗非班对超溶栓时间窗老年急性缺血性脑卒中患者的疗效分析

目的 探讨急性缺血性脑卒中(acute ischemic stroke,AIS)超溶栓时间窗老年患者应用替罗非班的有效性及安全性.方法 选取2019年10月～2020年2月郑州市第一人民医院神经内科收治的超溶栓时间窗老年AIS患者150例,随机分为观察组75例和对照组75例,对照组给予常规药物治疗,观察组在常规药物治疗...     

急性缺血性脑卒中的治疗

<正>脑卒中已经成为我国致死率和致残率第一位的疾病,严重危害人们健康,而缺血性脑卒中占80%以上。急性缺血性脑卒中(AIS)的治疗很具挑战性,毕竟与心电图快速诊断急性心肌梗死不同,急性脑卒中除了临床症状外,还需要急诊头颅CT来区分缺血性还是出血性脑卒中;另外,AIS的治疗时间窗非常短暂,目前惟一证实有效的治疗是及时恢复闭塞血管的再通。年,试验证实了静脉用重     

基层医院阿替普酶静脉溶栓治疗急性缺血性脑卒中117例疗效分析

目的回顾性分析重组组织型纤溶酶原激活剂(rt-PA)静脉溶栓治疗超急性期缺血性脑卒中近期预后,探讨其在基层综合性医院使用的有效性及安全性。方法采用回顾性分析,选择2012年4月~2014年9月在玉田县医院神经内科住院的急性缺血性脑卒中患者187例,根据治疗不同分为低剂量组60例(rt-PA 0.6mg/kg),标准剂量组57例(rt-PA 0.9mg/kg),对照为组70例(未行rt-PA,仅常规治疗)。系统采集所有患者病历资料,均完成28d及90d随访。以改良的Rankin量表(mRS)评分0~1分为预后良好,分析各组有效性和安全性是否存在差异。结果低剂量组、标准剂量组和对照组出院和28d随访时预后良好率比较,差异无统计学意义(30.0%vs 31.6%vs 18.6%,P=0.182;38.3%vs 45.6%vs 27.1%,P=0.092),低剂量组和标准剂量组90d时预后良好率明显高于对照组(50.0%vs 52.6%vs 32.9%,P=0.047)。低剂量组、标准剂量组和对照组出血发生率比较,差异有统计学意义(5.0%vs 10.5%vs 0%,P0.05);低剂量组与标准剂量组出血发生率差异无统计学意义(P=0.314)。随访90d时,低剂量组、标准剂量组和对照组病死率比较,差异无统计学意义(5.0%vs 3.5%vs 4.3%,P0.05)。结论 rt-PA静脉溶栓可改善缺血性脑卒中患者90d预后,降低患者残疾,但有一定出血风险,低剂量rt-PA较标准计量出血少。     

亚低温治疗对缺血性卒中纤溶系统的影响

纤溶系统失衡参与了缺血性卒中的病理生理学过程.大多数学者认为缺血性卒中患者的纤溶活性降低,而部分学者认为其纤溶活性增高.亚低温是一种具有巨大潜能并通过多种机制发挥神经保护效应的治疗手段.动物实验证实,亚低温治疗能提高血浆纤溶活性并减少缺血区局部纤溶酶原激活物表达,但相关临床研究较少,而且多局限于亚低温联合其他治疗方法的安全性和协同性的研究.

Abstract：

The imbalance in the fibrinolytic system participates in the pathophysic-logical processes of ischemic stroke. Most researchers consider that the fibrinolytic activity decreases in patients with ischemic stroke, while others believe that it increases. Mild hypothermia is a therapeutic approach with great potential and plays the neuroprotective effect through a variety of mechanisms. Animal experiments have demonstrated that the treatment with mild hypothermia may increase the plasma fibrinolytic activity and decrease the expression of local plasminogen activator in ischemic area. Howere, the related clinical research studies are few, and most of them are limited in the safty and collaborative research of mild hypothermia combined with other treatment therapies.     

轻型急性缺血性脑卒中患者静脉溶栓治疗的有效性和安全性分析

目的探讨重组组织型纤溶酶原激活剂(rt-PA)治疗轻型急性缺血性脑卒中的有效性和安全性。方法收集2011年1月~2013年7月发病4.5h的轻型脑卒中患者108例,其中溶栓组38例,未溶栓组70例。将轻型脑卒中定义为入院时美国国立卫生研究院卒中量表(NIHSS)评分≤5分。治疗前和治疗后14dNIHSS评分判断疗效,90d随访时改良Rankins量表评分判断预后,比较2组颅内出血及症状性颅内出血发生率、疗效和预后。结果溶栓组和未溶栓组治疗后14d有效率分别为50.0%和35.7%,差异无统计学意义(P=0.15)。2组颅内出血发生率分别为5.3%和1.4%(P=0.28),症状性颅内出血发生率分别为2.6%和1.4%(P=1.00),病死率分别为5.3%和4.3%(P=0.82),差异均无统计学意义。溶栓组发病后90d预后良好率明显高于未溶栓组(63.2%vs24.3%,P0.01)。结论 rt-PA静脉溶栓用于治疗轻型脑卒中患者安全有效。     

急性缺血性卒中机械取栓治疗的现状

在出现不可逆性神经细胞损伤之前迅速安全地再通血管、恢复血流以挽救缺血半暗带组织,是急性缺血性卒中（acute ischemic stroke, AIS ）的主要治疗目标。目前,在AIS早期开通血管的方法主要是静脉溶栓,但由于其治疗时间窗短、血管再通率低、出血并发症发生率高等原因,效果常不令人满意。近年来,随着机械取栓装置的研发及介入技术的发展,使得AIS的治疗时间窗显著延长,血管开通率显著提高,临床转归显著改善,机械取栓治疗已显示出良好的应用前景。     

缺血性脑血管病纤溶活性和血清同型半胱氨酸含量测定的临床意义

目的　探讨缺血性脑血管病 (ICVD)患者血浆纤溶活性和血清同型半胱氨酸 (Hcy)含量的变化及其临床意义。方法　入选ICVD患者 86例 (ICVD组 ) ,根据病情又分为短暂脑缺血发作 (TIA)组 14例 ,脑梗死组 72例 ,并入选非脑血管病患者 4 3例作为对照组 ,分别采用产色法测定血浆纤溶酶原 (Plg)、组织型纤溶酶原激活物 (t PA)、纤溶酶原激活抑制物 1(PAI 1)活性 ,荧光偏振光法测定血清Hcy,电化学发光法测定叶酸 ,同时常规测定血脂水平。结果　ICVD组 ,TIA患者和脑梗死患者血浆Plg、t PA活性均较对照组显著降低 (P <0 .0 5 )。ICVD组血清Hcy水平较对照组明显升高 (P <0 .0 1) ,t PA活性降低和高Hcy对ICVD的发生均有显著作用。结论　t PA活性降低和高Hcy分别是ICVD的独立危险因素     

Potential use of therapeutic ultrasound in ischemic stroke treatment

Systemic treatment with rtPA approved for a 3-hour window is the only established causal therapy for acute stroke in the United States and Canada. Thrombolytic therapy with rtPA demonstrated a small, although significantly reduced morbidity, in a limited number of highly selected patients. As recently shown, intraarterial application is favorable and opens the window of treatment up to 6 hours. The combination of ultrasound with thrombolytic agents may further enhance the potential benefit by means of enzymatic-mediated thrombolysis, which has been demonstrated in different in vitro and in vivo experiments for an accelerated recanalization of occluded peripheral and coronary vessels. Whereas no or only small attenuation of ultrasound can be expected through skin and chest, intensity will be significantly attenuated if penetration of the skull is required. The transcranial penetration of ultrasound increases when the frequency is decreased to 20 kHz and may be transmitted through the skull transtemporally with tolerable attenuation up to 200 kHz. This results in efficacy in vitro with low intensities of 0.5-2.0 W/cm(2) systemic treatment with rtPA approved for a 3-hour window in the nonfocused ultrasound field. Application of ultrasound insonation increased rtPA-mediated thrombolysis up to 20% in a static model; meanwhile, it enhanced the recanalization rate from 30%-90% in a flow model. In vitro results suggest that 1 MHz ultrasound with 0.5 W/cm(2), established for diagnostic purposes, may already enhance rtPA- mediated thrombolysis. Before therapeutic ultrasound can be tested clinically in acute stroke, safety of transcranial exposure of the brain has to be confirmed. To date, animal experiments suggested no harm to the blood brain barrier or systemic heating with 2 W/cm(2). This combined treatment is one perspective in optimizing therapy in acute stroke within the acute phase and may be applied easily with few limitations.     

Melatonin attenuates the postischemic increase in blood-brain barrier permeability and decreases hemorrhagic transformation of tissue-plasminogen activator therapy following ischemic stroke in mice

Melatonin protects against transient middle cerebral artery (MCA) occlusion and may be suited as an add-on therapy of tissue plasminogen activator (t-PA) thrombolysis. Herein, we examined whether melatonin would reduce postischemic increase in the blood-brain barrier (BBB) permeability and, therefore, attenuate the risk of hemorrhagic transformation after t-PA therapy in experimental stroke. Twelve mice were subjected to transient occlusion of the MCA for 1 hr, followed by 24 hr of reperfusion. Melatonin (5 mg/kg, i.p.) or vehicle was given at the beginning of reperfusion. BBB permeability was evaluated by quantitation of Evans Blue leakage. An additional 32 mice underwent photothrombotic occlusion of the distal MCA, and were administered vehicle or t-PA (10 mg/kg, i.v.), alone or in combination with melatonin (5 mg/kg, i.p.), at 6 hr postinsult. The animals were then killed after 24 hr for the determination of infarct and hemorrhage volumes. Relative to controls, melatonin-treated animals had significantly reduced BBB permeability (by 52%; P < 0.001). Additionally, we found that at 6 hr after photo-irradiation, either t-PA or melatonin, or a combined administration of t-PA plus melatonin, did not significantly affect brain infarction (P > 0.05), compared with controls. Mice treated with t-PA alone, however, had significantly increased hemorrhagic formation (P < 0.05), and the event was effectively reversed by co-treatment with melatonin (P < 0.05). Thus, melatonin improved postischemic preservation of the BBB permeability and a decreased risk of adverse hemorrhagic transformation after t-PA therapy for ischemic stroke. The findings further highlight melatonin's potential role in the field of thrombolytic treatment for ischemic stroke patients.     

单核细胞组织因子在急性缺血性脑卒中的动态变化

目的观察急性缺血性脑卒中(AIS)患者急性期及恢复期组织因子(TF)的变化。方法选择发病48 h内的AIS患者30例为AIS组,健康体检者61例为对照组。采用RT-PCR检测单核细胞TF mRNA;采用ELISA法检测血浆TF抗原。结果与对照组比较,AIS组急性期患者单核细胞TF mRNA(0.254±0.04 vs 0.312±0.09)和血浆TF抗原[(197.18±94.91)ng/L vs(276.64±106.01)ng/L]均明显增高,呈同步上升趋势(P<0.05);与急性期比较,AIS组恢复期单核细胞TF mRNA及血浆TF抗原呈同步下降,差异均有统计学意义(P<0.05)。AIS组恢复期血浆TF抗原与对照组比较差异无统计学意义(P>0.05)。结论 AIS患者发作期血液呈高凝状态,血栓形成风险增加;动态观察AIS患者单核细胞TF mRNA与血浆TF抗原含量,对了解疾病的发生、发展有辅助作用。     

阿替普酶静脉溶栓前应用依达拉奉对老年急性脑梗死预后的影响

目的 探讨老年急性脑梗死病人在应用阿替普酶(recombinant tissue plasminogen activator,rt-PA)静脉溶栓前预先使用依达拉奉的有效性和安全性.方法 采用回顾性分析的方法,纳入2014～2018年南京医科大学第二附属医院脑卒中登记系统中接受rt-PA静脉溶栓及依达拉奉联合治疗的老年...     

Tissue plasminogen activator levels in different types of polycythemia

The plasma level of tissue plasminogen activator antigen (t-PA-Ag) was examined in 86 patients with polycythemia (29 polycythemia vera, 11 secondary polycythemia and 46 with spurious polycythemia) and 24 healthy volunteers. Tissue plasminogen activator antigen was significantly decreased in patients with polycythemia vera in comparison with healthy controls. On the other hand, in patients with spurious polycythemia and secondary polycythemia t-PA-Ag concentration was significantly increased. There was no significant difference in t-PA-Ag levels in polycythemic patients with or without thromboembolic disease. A significant correlation was detected between t-PA-Ag level and hemoglobin or hematocrit concentration in patients with polycythemia vera (p = 0.02, r = 0.43). However, in patients with secondary polycythemia and spurious polycythemia, no significant correlation between t-PA-Ag and hemoglobin level was found. Plasminogen activator inhibitor (PAI) levels in patients with polycythemia vera and healthy volunteers did not differ significantly.     

Comparison of Argatroban and Hirudin for the Reperfusion of Thrombotic Arterial Occlusion by Tissue Plasminogen Activator

Despite theoretical advantages of direct thrombin inhibitors, recent clinical studies failed to show the superiority of hirudin over heparin in patients with acute coronary syndromes. However, these inhibitors have important in vitro differences for the inhibition of clot-bound thrombin that may translate into different in vivo relative efficacy. The effects of two direct thrombin inhibitors, argatroban and hirudin, on the reperfusion of thrombotic arterial occlusion by t-PA were compared. In anesthetized rabbits thrombotic occlusion was induced in the femoral artery. t-PA, aspirin, and various doses of argatroban (1.25, 2.5, and 5.0 mg/kg/h) or hirudin (2.5 and 5.0 mg/kg/h) were administered (six animals in each group). Blood flow was measured for 4 hours. Animals treated with 2.5 mg argatroban more rapidly achieved full reperfusion than those treated with high-dose argatroban or hirudin (P < 0.05). At the doses that induced comparable prolongation of bleeding time, argatroban showed a significantly faster and higher level of reperfusion than hirudin. In animals treated with hirudin, there was a positive correlation between the aPTT and the mean reperfusion blood flow (r = 0.70, P < 0.05). In animals treated with argatroban, this correlation did not exist and the high-dose argatroban was paradoxically less effective in promoting thrombolysis despite greater anticoagulation effects. In this animal model of arterial thrombosis, argatroban was more effective than hirudin in inducing rapid, full reperfusion with t-PA. Although they are both direct thrombin inhibitors, these two agents showed important dose-related differences in efficacy and anticoagulant effects.