艾通立早期静脉溶栓治疗急性脑梗死--附100例病例分析

目的：评价重组组织型纤溶酶原激活剂(rt-PA)艾通立对急性脑梗死早期静脉溶栓治疗的疗效及安全性，同时探讨国人应用rt-PA治疗的最佳剂量。方法：凡符合入选标准的患者随机分为A、B、C 3组，A组为rt-PA0．9mg／kg，B组为rt-PA 0．7mg／kg，C组作为对照组不用rt-PA。溶栓两组先将总量中的8mg静脉快速推入，剩余量在1h内用静脉泵输入，总量均不超过90mg。观察3组治疗后24h、90d神经功能缺损评分，及90d日常生活能力指数(Barthel)，同时观察3组治疗后30d脑出血率及病死率。结果：A组溶栓后24h和90d治愈及显效率为41．18％和76．47％，90d Barthel指数为95～100分者占58．82％，30d脑出血率为8．82％，病死率为5．88％。B组溶栓后24h和90d治愈及显效率为39．39％和69．70％，90d Barthel指数为95～100分者占54．55％，30d脑出血率为9．09％，病死率为9．09％。C组治疗后24h和90d治愈及显效率为21．21％和30．30％，90d Barthel指数为95～100分者占21．21％，30d病死率为9．09％。90d溶栓组显效率(73．13％)明显高于对照组(30．30％，P=0．0017)，严重致残率分别为13．43％和24．24％。结论：急性脑梗死静脉应用rt-PA溶栓治疗是安全有效的，国外0．9mg／kg的剂量也适用于国人。     

穿支动脉区孤立性梗死静脉溶栓治疗研究

目的 对比穿支动脉区孤立性梗死与其他类型脑梗死经静脉rtPA溶栓治疗后出血转化及神经功能结局的差异,明确穿支动脉区孤立性梗死静脉溶栓的安全性和有效性.方法 回顾分析了浙江大学医学院附属第二医院神经内科前瞻性收集的2009.06-2011.04期间接受静脉rtPA溶栓治疗的缺血性中风患者资料,包括性别、年龄、既往史、溶栓时间、基线NIHSS、血压、血糖、电解质、凝血谱、心电图、头颅MRI、颅内外MRA(或CTA)等,按照中国缺血性中风亚型(CISS)标准1予以病因分组.结果 共75例患者接受静脉rtPA治疗,年龄(67.4±12.7)岁,女性25例,占33.3％;溶栓前NIHSS(12.3±6.4)分;发病至溶栓时间:(239.6±97.5)min; 72例(96％)在24 h接受多模式MRI复查.共24例(32％)示溶栓后出血转化,4例(5.3％)为症状性出血.22例(29.3％)患者为穿支动脉区域孤立性梗死,仅1例(1.3％)发生出血转化.Logistic回归分析发现,穿支动脉区孤立性梗死明显降低溶栓后的出血转化风险(OR=0.075,95％CI:0.008～0.663; P=0.020).并发现,82％的穿支动脉区孤立性梗死患者的1月mRS评分≤2,其神经功能结局较其梗死好(P＜0.01).结论 穿支动脉区域孤立梗死患者相对于其他类型脑梗死患者在经静脉rtPA溶栓治疗后,显示出更低的出血转化率和较好的神经功能结局,故对 此类患者的静脉溶栓治疗可更积极.     

Decrease in blood pressure after intravenous administration of urapidil during recombinant tissue plasminogen activator thrombolysis for acute ischemic stroke

BACKGROUND: In patients who are candidates for IV recombinant tissue plasminogen activator (rtPA) thrombolysis for the treatment of acute ischemic stroke, blood pressure (BP)-lowering therapy is sometimes needed for systolic BP >185 mm Hg or diastolic BP >110 mm Hg. However, there is vast uncertainty regarding the appropriate choice of an antihypertensive agent. CASE SUMMARY: A 68-year-old Algerian woman (height, 161 cm; weight, 68 kg; body mass index, 26 kg/m2) was admitted to the Cardiology Unit of Amiens University Hospital, Amiens, France, for the assessment of nonvalvular atrial fibrillation. She was prescribed furosemide 40 mg/d to treat a slight left cardiac insufficiency. On day 10 of admission, the patient developed left-sided weakness. Neurologic examination revealed left hemiparesis. A computed tomography scan of the head showed no abnormality. Approximately 90 minutes after onset of the neurologic deficit, the patient had a BP of 180/100 mm Hg in both arms, an irregular pulse >75 bpm, and normal heart sounds. The patient was transferred to the Neurovascular Unit. There were no cervical or femoral bruits in this patient. During neurologic examination, the patient was alert and showed no signs of major cognitive deficit. The neurologic examination did reveal, however, minor hemisphere syndrome with left spatial neglect. There was a left lower-facial paresis. Motor examination revealed normal bulk with diminished tone in the patient's left arm and leg. Although there were no physical signs of dehydration, laboratory results revealed moderate signs of dehydration (total protein, 91 g/L [indicating proteinemia]; sodium, 147 mmol [indicating hypernatremia]; and elevated hematocrit, 42.0%). Considering the diagnosis of ischemic stroke and the duration of the symptoms (<3 hours), IV rtPA was administered. Approximately 10 minutes after intravenous rtPA administration, the patient's BP was 210/110 mm Hg, and an IV bolus of urapidil (20 mg) was administered. Approximately 2 minutes following urapidil administration, the patient developed neurologic worsening indicated by left-sided hemiplegia. Her BP was 105/60 mm Hg. The IV rtPA was immediately discontinued and volume replacement was started for 20 minutes. IV rtPA was restarted after the patient remained hemodynamically stable (15 minutes after rtPA was restarted). Following intensive physiotherapy, the patient was discharged on anticoagulation with a favorable outcome. At her 6-month follow-up, the patient had fully recovered. CONCLUSION: We report a probable case of hypotension associated with IV bolus of urapidil administration during rtPA thrombolysis for acute ischemic stroke in an elderly patient also treated with diuretics.     

The use of intravenous recombinant tissue plasminogen activator in acute ischemic stroke

We sought to determine the frequency of use of intravenous (i.v.) recombinant tissue plasminogen activator (rt-PA) in patients presenting to our institution with acute ischemic stroke (AIS). This observational study involved keeping a log of all patients presenting to our institution with symptoms consistent with AIS who were potential candidates for emergency thrombolysis over a 3-year period. The log included brain computed tomography (CT) scan results, whether or not rt-PA was administered, and contraindications to thrombolysis. It also included each patient's time flow through the system, from symptom onset to decision time regarding (and administration of) thrombolytics. Over the 36-month period of the study, there were 142 patients who presented to the Emergency Department (ED) who initially were thought to be potential candidates for thrombolysis for AIS. Ninety-five (68.5%) of these 142 patients had a confirmed diagnosis of AIS. On further clarification of symptom onset, 77 (81%) of these 95 patients with AIS actually presented within 3 h, and 17 (22%) of these 77 patients met criteria for thrombolysis and had no contraindications. All 17 (100%) patients with AIS presenting within 3 h of onset and without contraindications received i.v. rt-PA in the ED. In conclusion, i.v. rt-PA can be administered for AIS within the 3-h window if a hospital is committed to providing this treatment. Thrombolysis remains a treatment for a minority of AIS patients.     

伴心房颤动的急性脑梗死患者静脉溶栓的疗效

目的 观察伴心房颤动的急性脑梗死患者使用重组组织型纤溶酶原激活物(rt-PA)静脉溶栓的疗效.方法 连续收集发病时间＜4.5h的94例应用rt-PA静脉溶栓治疗的急性脑梗死患者,将64例无心房颤动患者作为非心房颤动组,30例伴心房颤动患者作为心房颤动组,并收集同一时段30例未行溶栓治疗的伴有心房颤动的急性脑梗死患者作为对照组,比较3组患者治疗前及治疗后7d的美国国立卫生研究院卒中量表(NIHSS)评分,观察颅内出血(ICH)和症状性颅内出血(SICH)的发生率,采用改良Rankin量表(mRS)对3组患者3个月预后进行分析.结果 心房颤动组和非心房颤动组溶栓后7d的NIHSS评分较溶栓前显著降低(P＜0.05或P＜0.01);对照组治疗前后NIHSS评分比较差异无统计学意义(P＞0.05);心房颤动组的ICH发生率高于非心房颤动组(26.7％vs.9.4％,P＜0.05),而两组之间SICH发生率差异无统计学意义(13.3％vs.6.3％,P＞0.05);心房颤动组、非心房颤动和对照组3个月预后良好的比例分别为40.0％、45.3％和16.7％,心房颤动组和非心房颤动组的3个月预后良好比例差异无统计学意义(P＞0.05),均明显高于对照组(P＜0.05或P＜0.叭);心房颤动组、非心房颤动组和对照组预后极差的比例分别为20.0％、18.8％和33.3％ (P ＞0.05).结论 伴有心房颤动的急性脑梗死患者rt-PA静脉溶栓治疗是安全有效的.     

小剂量重组组织型纤溶酶原激活剂静脉加速给药法治疗急性心肌梗死

目的评价小剂量重组组织型纤溶酶原激活剂（rt-PA）50 mg加速给药法对急性心肌梗死（AMI）溶栓的疗效及安全性.方法共入选符合条件的患者236例.随机分为观察组与对照组,观察组120例：小剂量rt-PA加速给药,rt-PA给予8 mg静脉注射,继之42 mg在60分钟内静脉滴注;对照组116例：rt-PA给予8 mg静脉注射,继之42 mg在90分钟内静脉滴注;所有患者均给予静脉肝素治疗,以用药后临床2小时再通指标为主要终点.结果观察组冠脉再通率高于对照组（84.1%vs 70.7%,P＜0.05）两组出血率无差别,两组各有1例颅内出血,但差异无统计学意义.结论小剂量rt-PA加速给药治疗AMI疗效更好,且同样安全.     

静脉低剂量重组组织型纤溶酶原激活物治疗短暂性脑缺血发作的临床对照研究

目的研究和分析静脉低剂量重组组织型纤溶酶原激活物(rt-PA)治疗短暂性脑缺血发作(TIA)的临床效果。方法选取86例TIA患者作为研究对象,根据治疗方式将其分为观察组41例(应用低剂量rt-PA静脉溶栓治疗联合阿司匹林抗血小板治疗)和对照组45例(应用阿司匹林抗血小板治疗)。比较2组患者入院时、治疗第1、3、7、14天时组织型纤溶酶原激活物(t-PA)、纤溶酶原激活物抑制物-1(PAI-1)水平。比较2组患者治疗各时段的TIA控制率,对2组患者进行为期1年的随访,比较患者转为急性脑梗死的比例。结果治疗第1、3天,观察组患者的血浆t-PA水平显著高于对照组(P0.05)。在治疗前、后各时点,2组患者的血浆PAI-1水平的差异均无统计学意义(P0.05)。2组患者各时段TIA控制率的差异无统计学意义(P0.05)。观察组和对照组分别有2例和4例患者于随访期内转为急性脑梗死,2组患者转为急性脑梗死比例的差异无统计学意义(P0.05)。结论在阿司匹林抗血小板治疗的基础上采用静脉滴注低剂量rt-PA进行溶栓治疗,能够提高TIA初期患者的血浆t-PA水平,有助于降低血栓形成风险,但对于患者的血浆PAI-1水平、近期疗效和远期预后的作用并不显著。     

Intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) in acute lower limb ischaemia

For various reasons some patients are unable to undergo intra-arterial thrombolysis for acute limb ischaemia. This interventional case series study prospectively evaluated the effect of thrombolytic treatment with 100 mg recombinant tissue plasminogen activator (rt-PA), administered intravenously, in patients with acute thrombosis of the lower limb arteries and onset of symptoms within 12 h prior to treatment. During a 3-year period (2007-2009), 18 of 86 patients satisfied the inclusion criteria and were included in the study (age range 65-80 years; 11 women). Complete and partial thrombolysis was observed in eight (44.4%) and six (33.3%) patients, respectively. All patients experienced clinical improvement. There were no amputations during the 36-month follow-up period and no haemorrhagic complications in the first 30 days post-treatment. Five patients died (27.8%) during follow-up from unrelated causes. This small study demonstrated that thrombolytic treatment with intravenous rt-PA in selected patients with acute limb ischaemia is feasible.     

Coronary thrombolysis and infarct size reduction after intravenous infusion of recombinant tissue-type plasminogen activator in nonhuman primates.

Occlusive thrombus was produced by thrombin-induced coagulation in the left anterior descending coronary artery (LAD) of 16 open-chest baboons. In six control animals, occlusive thrombosis persisting over a period of 4 h as evidenced by coronary arteriography resulted in large transmural infarction (63.1 +/- 3.5% of the perfusion area). In 10 animals, tissue-type plasminogen activator obtained by recombinant DNA technology (rt-PA) was infused systemically at a rate of 1,000 IU (10 micrograms)/kg per min for 30 min after 30-80 min of coronary thrombosis. Reperfusion occurred within 30 min in nine animals. In one animal, intravenous infusion was followed by an intracoronary infusion at the same rate, which resulted in thrombolysis within 8 min. In the rt-PA group, mean duration of occlusion before reperfusion was 77 +/- 24 min. Reocclusion occurred in one animal. Recanalization resulted in an overall reduction of infarct size (37.8 +/- 5.9%, P less than 0.05 versus controls). Residual infarction was related to the duration of occlusion (r = 0.80, P less than 0.01). Reperfusion was associated with reduced reflow. Myocardial blood flow in the perfusion area of the LAD was only 70% of normal after 4 h despite perfect angiographic refilling. The infusion of rt-PA was not associated with systemic activation of the fibrinolytic system, fibrinogen breakdown, or clinically evident bleeding. It is concluded that intravenous infusion of rt-PA may recanalize thrombosed coronary vessels without inducing systemic lysis. The extent of residual infarction is closely related to the duration of coronary artery occlusion before thrombolysis.     

抗血小板治疗对重组组织型纤溶酶原激活剂静脉溶栓所致出血性转化的影响

目的 评价抗血小板聚集治疗对急性缺血性脑卒中重组组织型纤溶酶原激活剂(rt-PA)静脉溶栓后出血性转化(HT)的影响.方法 将我院的111例急性缺血性脑血管病溶栓患者,根据溶栓前是否使用抗血小板聚集药物,分为对照组(未使用抗血小板聚集药物)30例、阿司匹林(ASA)组28例、氯吡格雷(CLP)组28例、阿司匹林加氯吡格雷(ASA+CLP)组25例,统计各组溶栓后HT的发生率及90天后改良的Rankin评分,并进行统计学比较.结果 对照组、ASA组、CLP组、ASA+CLP组HT发生率分别为10.0％、21.4％、17.9％、48.0％.ASA+ CLP组HT的发生率与对照组差异有统计学意义,其余各组间差异无统计学意义;ASA组和CLP组与ASA+ CLP组比较Rankin评分差异有统计学意义.结论 急性缺血性脑血管病溶栓前单用ASA或CLP未增加rt-PA溶栓后HT的发生率,溶栓前联合使用阿司匹林及氯吡格雷显著增加rt-PA溶栓后HT的发生率,各组HT的发生未增加90天后溶栓患者的残疾率.     

重组组织型纤溶酶原激活物静脉溶栓治疗脑梗死的早期转归及护理对策

目的 探讨重组组织型纤溶酶原激活物(recombinant tissue plasminogen activator,rtPA)静脉溶栓治疗急性脑梗死的早期转归及护理对策.方法 回顾性分析42例急性脑梗死患者的临床资料,其中观察组(rtPA组)15例,应用rtPA静脉溶栓治疗;对照组27例,未进行溶栓治疗.在治疗后14d时应用改良Rankin量表进行临床疗效评价,将mRS评分≤2分定义为转归良好.结果 观察组治疗14 d时转归良好率显著高于对照组(P＜0.05).治疗14d时颅内出血的发生率、病死率两组差异无显著意义(P＞0.05).结论 rtPA静脉溶栓治疗急性脑梗死安全、有效.护士掌握rtPA静脉溶栓治疗的护理技术,有助于提高脑梗死的溶栓率,减少溶栓并发症的发生,改善患者的预后.     

小剂量重组组织型纤溶酶原激活物与尿激酶治疗急性心肌梗死的对比研究

目的：评价小剂量重组组织型纤溶酶原激活物（ｒｔＰＡ）静脉溶栓治疗国人急性心肌梗死（ＡＭＩ）的疗效及安全性。方法：６６例ＡＭＩ患者随机分为ｒｔＰＡ组３１例及尿激酶（ＵＫ）组３５例,分别应用ｒｔＰＡ及ＵＫ治疗。结果：心肌梗死相关血管再通率ｒｔＰＡ组８０．６％与ＵＫ组４８．６％比较,Ｐ＜０．０５;４周住院病死率ｒｔＰＡ组０与ＵＫ组８．６％比较,Ｐ＜０．０５;而２组间出血发生率无差异。结论：小剂量ｒｔＰＡ治疗ＡＭＩ血管再通率高,出血并发症少,可降低ＡＭＩ早期病死率,是一种安全有效的溶栓剂     

Efficacy of a new mutated recombinant tissue-type plasminogen activator in beagles with acute coronary artery thrombi

BACKGROUND:

Development of new coronary thrombolytic agents is hot in the market. A new drug, mutated recombinant tissue-type plasminogen activator (rtPAm), is the product of mutation of tPA by changing binding loci with plasminogen activator inhibitor (PAI)-1 to reduce the degradation. In vitro test has demonstrated that the activity of rtPAm is much higher than rtPA in the absence of PAI. The present study is to observe the efficacy of mutated recombinant tissue-type plasminogen activator (rtPAm) in coronary thrombolytic therapy.

METHODS:

A total of 30 adult beagles were equally divided into 5 groups after thrombi: vehicle group, urokinase group, rtPAm low-dose group, rtPAm medium-dose group, and rtPAm high-dose group. Thrombolytic effect and myocardial infarction were observed after thrombolytic therapy.

RESULTS:

In the urokinase group, time to reperfusion was (15.8±3.8) minutes. TIMI 2 flow was demonstrated in 4 beagles, TIMI 3 flow in 2, and re-occlusion in 4 after 90 minutes respectively. In the low-dose rtPAm group, time to reperfusion was (15±4.5) minutes; TIMI 2 flow was demonstrated in 2 beagles, TIMI 3 flow in 4, and re-occlusion in 2 after 90 minutes. In the high-dose rtPAm group, time to reperfusion was (7.5±2.6) minutes. None of the beagles showed re-occlusion after 90 minutes. The infarction areas were (2.1+0.9)% in the medium-dose rtPAm group and (0.7+0.4)% in the high-dose rtPAm group, which decreased significantly than those in the low-dose rtPAm group. The aggregation rate in the medium-dose and high-dose rtPAm groups decreased significantly than that in the urokinase group.

CONCLUSION:

rtPAm may serve as a thrombolytic agent with platelet-targeted fibrinolysis and antiplatelet aggregation activities.KEY WORDS: Urokinase, RtPA, Thrombi, D-dime, Platelet aggregation     

Plasminogen activator and plasminogen activator inhibitor activities in men with coronary artery disease

Although elevated levels of plasminogen activator inhibitor-1 (PAI-1) have been associated with the development of myocardial infarction, the correlation between the presence of coronary artery disease and increased levels of PAI-1 is controversial. The present study evaluated the association between angiographically-documented coronary artery disease and plasma levels of PAI-1 and tissue-type plasminogen activator (t-PA) in 65 men (ages 35 to 65 years) who had no previous history of myocardial infarction, angioplasty, or other medical illnesses. PAI-1 activity in these 65 patients was inversely correlated with t-PA activity, which was measured before and after venous occlusion. PAI-1 activity correlated positively with levels of triglycerides. There was a significant negative correlation between PAI-1 activity and levels of high-density lipoprotein. Each patient was placed in one of five groups according to the severity of coronary atherosclerosis, which ranged from normal vessels (group I) to greater than 50% occlusion of three vessels (group V). There were no significant differences among the five groups with respect to mean activity of PAI-1 (p = 0.98) or t-PA activity measured before venous occlusion (p = 0.22) or after occlusion (p = 0.70). T-PA and PAI-1 activities in these five groups were not different from those in 35 healthy men. These data indicate that there is no association between activities of PAI-1 or t-PA and coronary artery disease in this well-characterized male population.     

重组组织型纤溶酶原激活物静脉溶栓治疗超早期脑梗死的临床应用研究

目的研究重组组织型纤溶酶原激活物（r-tPA）治疗早期脑梗死的临床应用。方法比较r-tPA治疗组和对照组脑梗死患者治疗有效率和神经功能改善程度。结果r-tPA治疗组治疗有效率80．00％，对照组有效率55．00％，2组比较差异有显著性（P〈0．05）；从治疗1d后起，r-tPA治疗组患者美国国立卫生研究院卒中量表（NIHSS）评分均明显低于对照组（均为P〈0．05）。结论在严格控制适应证的前提下，r-tPA治疗早期脑梗死患者有效而且安全；r-tPA治疗早期脑梗死患者可不依赖头颅MRI和脑动脉介入技术，能够在一般医院开展。     

Influence of the fast-acting inhibitor of plasminogen activator on in vivo thrombolysis induced by tissue-type plasminogen activator in rabbits. Interference of tissue-derived components.

The influence of endotoxin-induced elevated plasma levels of the fast-acting inhibitor of plasminogen activator (PA-inhibitor) on thrombolysis was investigated in rabbits with a jugular vein thrombus. Infusion of human tissue-type plasminogen activator (t-PA) produced similar degrees of thrombolysis in control and endotoxin-treated rabbits, although no free t-PA could be demonstrated in plasma of endotoxin-treated animals. Infusion of t-PA in an extracorporeal arteriovenous shunt resulted in loss of thrombolytic activity in endotoxin-treated animals but not in control animals. Blood clots superfused in vitro with mixtures of t-PA and normal plasma lysed in contrast to clots superfused with t-PA and PA-inhibitor-rich plasma. However, addition of rabbit lung slices to the plasma surrounding the blood clot, reversed the inhibition of thrombolysis by PA-inhibitor-rich plasma. This indicates that tissue-derived factor(s) are involved in the regulation of in vivo thrombolysis. These hypothetical factor(s) are, however, very unstable in plasma, which has thus far precluded their further characterization.     

小剂量重组组织型纤溶酶原激活物与重组链激酶治疗急性心肌梗死的对比研究

目的 评价小剂量重组组织型纤溶酶原激活物（r-TPA)与国产重组链激酶（r-SK)治疗急性心肌梗死（AMI）的疗效,并比较二者的差异。方法 71例AMI患者,均采用静脉溶栓,随机分为r-TPA治疗组（36例）和r-SK治疗组（35例）。结果 梗死相关血管再通率r-TPA组为77．78％（28／36）,r-SK组为74．29％（26／35）P＞0．05,差异不显著;4周病死率r-TPA组为5．56％（2／36）,r-SK组为5．71（2／35）％,差异不显著（P＞0．05）;两组均未出现严重出血。但r-SK组过敏反应发生率为8．57％（3／35）,低血压发生率为2．86％（1／35）。结论 加速法使用国产r-SK治疗AMI,梗死相关血管再通率、4周病死率r-TPA与r-SK相似,但过敏反应及低血压发生率r-SK较r-TPA高,国产r-SK治疗AMI安全有效,无严重出血,费用较r-TPA低,值得临床推广使用。