Sixty-Minute Alteplase Protocol: A New Accelerated Recombinant Tissue-Type Plasminogen Activator Regimen for Thrombolysis in Acute Myocardial Infarction

Objectives. Our aim was to design and evaluate a new and easily administered recombinant tissue-type plasminogen activator (rt-PA) regimen for thrombolysis in acute myocardial infarction (AMI) based on established pharmacokinetic data that improve the reperfusion success rate.

Background. Rapid restoration of Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow is a primary predictor of mortality after thrombolysis in AMI. However, TIMI grade 3 patency rates 90 min into thrombolysis of only 50% to 60% indicate an obvious need for improved thrombolytic regimens.

Methods. Pharmacokinetic simulations were performed to design a new rt-PA regimen. We aimed for a plateau tissue-type plasminogen activator (t-PA) plasma level similar to that of the first plateau of the Neuhaus regimen. These aims were achieved with a 20-mg rt-PA intravenous (i.v.) bolus followed by an 80-mg i.v. infusion over 60 min (regimen A). This regimen was tested in a consecutive comparative trial in 80 patients versus 2.25 10⁶ IU of streptokinase/60 min (B), and 70 mg (C) or 100 mg (D) of rt-PA over 90 min. Subsequently, a confirmation trial of regimen A in 254 consecutive patients was performed with angiographic assessment by independent investigators of patency at 90 min.

Results. The comparative phase of the trial yielded, respectively, TIMI grade 3 and total patency (TIMI grades 2 and 3) of 80% and 85% (regimen A), 35% and 50% (B), 50% and 55% (C) and 60% and 70% (D). In the confirmation phase of the trial, regimen A yielded 81.1% TIMI grade 3 and 87.0% total patency. At follow-up angiography 7 (4.1%) of 169 vessels had reoccluded. In-hospital mortality rate was 1.2%. Nadir levels of fibrinogen, plasminogen and alpha₂-antiplasmin were 3.6 ± 0.8 mg/ml, 60 ± 21% and 42 ± 16%, respectively (mean ± SD). Fifty-seven patients (22.4%) suffered from bleeding; 3.5% needed blood transfusions.

Conclusions. The 60-min alteplase thrombolysis in AMI protocol achieved a TIMI grade 3 patency rate of 81.1% at 90 min with no indication of an increased bleeding hazard; it was associated with a 1.2% overall mortality rate. These results are substantially better than those reported from all currently utilized regimens. Head to head comparison with established thrombolytic regimens in a large-scale randomized trial is warranted.     

重组组织型纤溶酶原激活药静脉溶栓治疗发病4.5 h内急性脑梗死的疗效和安全性

 目的 观察重组组织型纤溶酶原激活药(rt-PA)静脉溶栓治疗发病4.5 h内急性脑梗死的疗效和安全性。方法 选择2012-07至2016-09武警北京总队医院收治的发病在4.5 h内急性脑梗死患者81例,根据患者及家属意愿分为溶栓组和对照组,溶栓组 58 例给予rt-PA 0.9 mg/kg静脉溶栓;对照组23 例采用抗血小板聚集药物等治疗;比较溶栓和常规治疗前和治疗后24 h、7 d及14 d 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 24 h、7 d 及 14 d 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)。溶栓组临床总有效率为86.21％,对照组为52.17％。溶栓组脑出血发生率为10.34％,其中症状性脑出血发生率3.45％;对照组脑出血发生率8.69％,其中症状性脑出血发生率4.35％。溶栓组和对照组病死率分别为5.17%和8.69％,差别无统计学意义(P=0.587)。结论 急性脑梗死患者4.5 h 内给予rt-PA 静脉溶栓治疗较常规治疗有效。     

大剂量人体白蛋白和硫酸镁对溶栓后脑组织的保护与促进修复作用

目的 评价rt-PA溶栓治疗联合大剂量人体白蛋白与硫酸镁延长溶栓时间窗的可能性和可靠性.方法 健康雄性成年SD大鼠40只,对血栓法建立的急性大鼠大脑中动脉栓塞(MACO)模型随机分为4组.A组:缺血3 h,rt-PA单纯溶栓(对照组,10只);B组:缺血6 h,rt-PA单纯溶栓(10只);C组:缺血6 h,rt-PA溶栓 人体白蛋白(10只);D组:缺血6 h,rt-PA溶栓 人体白蛋白 硫酸镁(10只).rt-PA(10 mg/kg)与20%人体白蛋白(2.5 g/kg)分别从大鼠股静脉缓慢注入,人体白蛋白在脑缺血3 h开始注射,1 h内完成;5%硫酸镁溶液(500 mg/kg)在脑缺血3 h和18 h自腹腔注射.于治疗前、治疗后24 h、7 d、14 d行MRI检查,在治疗14 d MRI检查结束后立即处死,行病理学检查(包括光镜、电镜和免疫组化)、激光扫描共聚焦显微镜检查.结果 ①溶栓治疗后14 d与治疗前比较,A、B、C、D 4组中脑梗死体积分别缩小5.07%、2.58%、10.18%和35.40%,以D组缩小最为明显.②4组间梗死边缘区相对脑血流量(rCBV)在4个时间段分别比较差异均有统计学意义(P均<0.05).③4组中大鼠的生存时间以D组最长,以B组最短,4组之间存活时间比较差异无统计学意义(F=0.188,P=0.904).④激光扫描共聚焦显微镜显示C组、D组脑梗死边缘区微血管轻度扩张,有少量、局限的荧光物质渗出,较B组明显减少.⑤免疫组化显示C组与D组脑梗死边缘区胶质纤维酸性蛋白(GFAP)增生活跃,与B组比较增生层较厚且密集.⑥电镜结果显示C组、D组神经元核形态基本正常,线粒体轻度肿胀.星形细胞足板轻度空泡化,较B组损害程度轻.结论 rt-PA溶栓治疗联合人体白蛋白、硫酸镁明显缩小脑梗死体积,提高脑梗死边缘区rCBV速率,促进星形细胞增生.研究表明rt-PA溶栓治疗联合大剂量人体白蛋白、硫酸镁,能有效地延长溶栓时间窗,可以延长至脑缺血 6 h内.     

rt-PA动脉内溶栓治疗急性脑梗死的临床研究

目的观察重组组织型纤溶酶原激活剂(rt-PA)动脉内溶栓(IAT)治疗急性脑梗死的疗效及并发症,分析预后相关因素。方法对12例发病后20h内的急性缺血性脑梗死患者行IAT治疗。血管再通程度根据“急性心肌梗死溶栓标准”(TIMI)分类。临床结果评价在溶栓后20d进行,根据改良的Rank分数(MRS)分为良好(MRS0～3)、不良(MRS4～6)两类。结果溶栓前1例为TIMI1,11例为TIMI0。溶栓后9例闭塞血管部分／完全再通,3例未再通。8例患者结果良好;4例不良结果;其中2例死亡。发生症状性脑出血1例,经治疗恢复良好。结论rt-PA用于急性脑梗死动脉溶栓,是安全可行的。     

Catheter-directed ultrasound-accelerated thrombolysis for the treatment of acute pulmonary embolism

Background

Systemic thrombolysis rapidly improves right ventricular (RV) dysfunction in patients with acute pulmonary embolism (PE) but is associated with major bleeding complications in up to 20%. The efficacy of low-dose, catheter-directed ultrasound-accelerated thrombolysis (USAT) on the reversal of RV dysfunction is unknown.

Materials and methods

We performed a retrospective analysis of 24 PE patients (60 ± 16 years) at intermediate (n = 19) or high risk (n = 5) from the East Jefferson General Hospital who were treated with USAT (mean rt-PA dose 33.5 ± 15.5 mg over 19.7 hours) and received multiplanar contrast-enhanced chest computed tomography (CT) scans at baseline and after USAT at 38 ± 14 hours. All CT measurements were performed by an independent core laboratory.

Results

The right-to-left ventricular dimension ratio (RV/LV ratio) from reconstructed CT four-chamber views at baseline of 1.33 ± 0.24 was significantly reduced to 1.00 ± 0.13 at follow-up by repeated-measures analysis of variance (p < 0.001). The CT-angiographic pulmonary clot burden as assessed by the modified Miller score was significantly reduced from 17.8 ± 5.3 to 8.7 ± 5.1 (p < 0.001). All patients were discharged alive, and there were no systemic bleeding complications but four major access site bleeding complications requiring transfusion and one suspected recurrent massive PE event.

Conclusions

In patients with intermediate and high risk PE, low-dose USAT rapidly reverses right ventricular dilatation and pulmonary clot burden.     

CT灌注成像在急性缺血性脑卒中rt-PA溶栓中的指导意义

目的 探讨CT灌注成像(CTP)在rt-PA静脉溶栓治疗急性缺血性脑卒中的价值.方法 25例急性缺血性脑卒中(发病时间<3h)患者行CTP检查组15例:见缺血半晴带应用rt-PA静脉溶栓组(见IP)10例,无缺血半暗带常规治疗组(无IP)5例.未行CTP检查应用rt-PA静脉溶栓组(对照组)10例.评价CTP指导下见IP组、无IP组和对照组患者疗效和预后.结果 见IP组rt-PA静脉溶栓后各时间段NIHSS评分与治疗前相比均有明显改善(P<0.001),而对照组NIHSS评分于24h、7d均无明显变化,直到30d后明显改善(P<0.01),而两组相比于24h后见IP组NIHSS评分明显低于对照组(P<0.05).见IP组未出现颅内出血及死亡病例,且Barthel指数明显高于对照组.对照组颅内出血率44%,死亡率11%.无IP组常规抗栓治疗NIHSS评分于24h、7d均无明显变化,30d后明显改善(P<0.01),与对照组相比无明显差异(P>0.05).结论 急性缺血性脑卒中在发病3h内,经CTP检查见IP者应用rt-PA溶栓安全、效果可靠;无IP者不予溶栓治疗而给予常规抗栓治疗,即能避免盲目溶栓所带来的出血及死亡风险,还能取得较好的远期疗效.     

超早期重组组织型纤溶酶原激活物溶栓治疗脑梗死的临床研究

目的 探讨重组组织型纤溶酶原激活物（rt—PA）静脉溶栓治疗超早期脑梗死的安全性与有效性。方法 按入选标准筛选合适患者21例进行溶栓，以相同时期非溶栓治疗的具有相同条件的患者20例为对照组，在溶栓前及溶栓后24h、21d按欧洲脑卒中神经功能缺损评分标准（ESS）进行评定，3个月时按Barthel指数进行评定。结果 溶栓组疗效优于对照组（P〈0．05）。溶栓组脑出血发生1例，预后仍然良好。两组患者均无死亡病例。结论 rt—PA静脉溶栓治疗超早期急性脑梗死安全、有效。     

院前静脉溶栓治疗急性心肌梗死的临床随机对照研究

目的　评价重组组织型纤溶酶原激活剂 (rt PA)在院前救治急性心肌梗死 (AMI)的近期临床治疗效果 ,并探讨在院前对AMI患者进行静脉溶栓治疗的安全性和可行性。方法　对所收治的AMI患者进行分组 ,均给予rt PA( 5 0mg)进行静脉溶栓治疗 ,对比两者的冠状动脉再通率以及发病至溶栓时间延迟对rt PA静脉溶栓疗效的影响。结果　从患者发病至进行溶栓治疗的时间间隔 ,院前组平均比院内组缩短 2 .2小时 [( 2 .9± 1.4)小时比 ( 5 .1± 1.1)小时 ] ,P <0 .0 5 ;院前治疗组的冠状动脉总再通率为 90 % ,明显高于院内治疗组的 61.8% (P <0 .0 5 )。结论　院前应用rt PA( 5 0mg)进行静脉溶栓治疗安全、可行。     

rt-PA静脉溶栓联合高压氧治疗急性脑梗死的效果观察

目的评价重组组织型纤溶酶原激活剂(rt-PA)静脉溶栓联合高压氧(HBO)治疗急性缺血性脑梗死的安全性和有效性。方法选取上海市浦东医院急性脑梗死患者78例,随机分为A组rt-PA溶栓治疗组38例和B组rt-PA联合HBO 40例。两组患者均在发病4.5h内采用rt-PA静脉溶栓治疗,B组患者在接受上述治疗后立即进高压氧舱进行治疗。两组患者疗程均为20d,分别在治疗24h、10d及20d采用NIHSS及ADL评分进行神经功能及日常生活能力评估,并通过患者发生再次脑梗、TIA发作、脑出血及死亡率进行治疗方案有效性及安全性评估。结果治疗前后2组NIHSS评分与ADL评分比较,治疗后24h、10d、20d2组评分与治疗前比较有显著性差异(P0.05),且呈时间依赖性;两个治疗组相比较,NIHSS评分在24h及20d时差异具有统计学意义(P0.05),ADL评分在20d时差异具有统计学意义(P0.05);A、B两组相比较,患者发生再次脑梗、TIA发作、脑出血及死亡率差异无统计学意义(P0.05)。结论 rt-PA联合HBO治疗急性期脑梗死与单用rt-PA的疗效相比,在超早期及长期治疗的效果较好,因此该治疗方法是安全有效的。     

Thrombolytic therapy in a patient with acute ischemic stroke caused by aortic dissection

The current medical literature indicates a poor outcome in patients with ischemic stroke in the presence of aortic dissection, especially in those who underwent thrombolytic therapy. We report a favorable outcome in a patient with acute stroke who received rt-PA and was later found to have Stanford type A aortic dissection.