重组组织型纤溶酶原激活剂溶栓改良方案治疗急性心梗疗效观察

用重组组织型纤溶酶原激活剂（ＲｅｃｏｍｂｉｎａｎｔＴｉｓｓｕｅＴｙｐｅＰｌａｓｍｉｎｏｇｅｎＡｃｔｉｖａｔｏｒ，ｒｔ－ＰＡ）改良方案（ｒｔ－ＰＡ１０ｍｇ在两分钟内静注，接住在４５分钟内以０．８８ｍｇ／ｍｉｎ速率滴注４０ｍｇ，滴完前５分钟作心电图，心肌酶检查，判定心肌再灌注，若心肌未获再灌注，冠脉未再通，则继续给予ｒｔ－ＰＡ以同样速率０．８８ｍｇ／ｍｉｎ滴注５０ｍｇ总剂量不超过１００ｍｇ，根据非介入性临床指标判断，心肌再灌注率９１．４％，未见严重出血并发症及住院期冠脉再堵塞，２３例ｒｔ－ＰＡ用量５０ｍｇ及９例用量１００ｍｇ获心肌再灌注，结果显示：改良方案可提高心肌再灌注率及降低费用，并且不增加出血并发症及住院期内冠脉再堵塞。     

急诊科内应用重组组织型纤溶酶原激活剂治疗急性心肌梗死44例临床分析

目的评价急诊科内应用重组组织型纤溶酶原激活剂（ｒｔ－ＰＡ）静脉溶栓治疗急性心肌梗死（ＡＭＩ）的疗效及安全性。方法４４例ＡＭＩ患者在急诊科内接受ｒｔ－ＰＡ静脉溶栓治疗。ｒｔ－ＰＡ总量原则为“三级剂量,开通则停”。即当临床显示血管再通时将剂量限制在５０ｍｇ、７５ｍｇ及１００ｍｇ,特殊情况适当加量。负荷量及余量输注速率视梗死部位而异。结果药物总量达５０ｍｇ、７５ｍｇ及１００ｍｇ时血管再通率分别为５９％、７７％及８４％。３例并发心源性休克患者剂量达１００ｍｇ后无再通且病情恶化,分别追加５０ｍｇ、５０ｍｇ及１００ｍｇ后血管再通且存活。总再通率为９１％。轻度出血率为２７％,无严重及颅内出血。结论提示在急诊科内应用ｒｔ－ＰＡ静脉溶栓治疗ＡＭＩ安全有效。     

急性心肌梗死溶栓患者凝血与纤溶系统的改变及临床意义

目的应用链激酶（ＳＫ）、重组链激酶（ｒ－ＳＫ）、尿激酶（ＵＫ）、重组组织型纤溶酶原激活物（ｒｔ－ＰＡ）溶栓治疗急性心肌梗死（ＡＭＩ）患者,比较其凝血与纤溶系统的动态变化。方法对４３例经溶栓治疗（ＳＫ８例,ｒ－ＳＫ１３例,ＵＫ１６例,ｒｔ－ＰＡ６例）的ＡＭＩ患者,分别于溶栓前后动态检测凝血酶原时间（ＰＴ）、活化的部分凝血活酶时间（ＡＰＴＴ）、纤维蛋白原（ＦＧ）、Ｄ二聚体（Ｄ－Ｄｉｍｅｒ）、纤溶酶原（ＰＬＧ）、α２抗纤溶酶（α２ＡＰ）、组织型纤溶酶原激活物（ｔ－ＰＡ）、组织型纤溶酶原激活物抑制物（ＰＡＩ－１）等指标的活性或含量。结果应用ＳＫ、ｒ－ＳＫ、ＵＫ、ｒｔ－ＰＡ溶栓治疗后,均会引起凝血活性的明显降低与纤溶活性的明显增高。ＳＫ与ｒ－ＳＫ对凝血与纤溶系统的影响略高于ＵＫ。ｒｔ－ＰＡ对ＦＧ含量影响低于另外３者（Ｐ值均＜００５）。结论凝血与纤溶活性的变化与溶栓疗效关系密切     

不同溶栓药物静脉溶栓治疗急性心肌梗塞的比较观察

对９０例发病１２小时以内的ＡＭＩ患者，分别给予ＵＫ、ＳＫ、ｒｔ－ＰＡ进行溶栓治疗，并辅以肝素、阿司匹林治疗。结果表明，ＵＫ组、ＳＫ组及ｒｔ－ＰＡ组的临床血管再通率分别为６７．５％、７３．３％、８５％。并发重度出血率ｒｔ－ＰＡ组为１５％，而另两组为０。     

国人小剂量重组织织型纤溶酶原激活剂与尿激酶治疗急性心肌梗塞随机对照研

目的 评价重组组织型纤溶酶原激活剂（ｒｔ－ＰＡ）５０ｍｇ对国人急性心肌梗塞（ＡＭＩ）溶栓治疗的疗效及安全性，并与国产尿激酶（ＵＫ）常用剂量的疗效进行对比。方法 该研究系在１７所医院进行的开放、多中心随机理平行对照试验。在５５例患作为ｒｔ－ＰＡ５０ｍｇ预试验完成后，研究继续进行，其人选合格患３２４例。符合条件的患随机分为ｒｔ－ＰＡ与ＵＫ两组：前后ｒｔ－ＰＡ给予８ｍｇ静脉注射，继之４２ｍｇ在９０     

急性大面积肺栓塞的重组组织型纤溶酶原激活剂静脉溶栓治疗

本文报道１例急性肺栓塞采用~（９９ｍ）Ｔｃ－Ｐ３５７标测肺动脉内新鲜血栓，并进行肺动脉造影，显示大块新鲜血栓堵塞于左、右肺动脉干的急性大面积肺栓塞，肺动脉压中度升高。选用重组组织型纤溶酶原激活剂（ｒｔ－ＰＡ）进行静脉溶栓治疗。溶栓后再次行肺动脉造影，结果显示大块血栓基本溶解，部分肺动脉的小分支内仍有残余血栓，肺动脉压降至正常。本例表明，急性肺栓塞如能得到及时诊断和治疗，可迅速逆转大面积肺栓塞所致的血液动力学障碍，~（９９ｍ）Ｔｃ－Ｐ３５７是最先进的、准确的诊断急性肺栓塞的检测手段，ｒｔ－ＰＡ是一安全、有效的溶栓药物。     

rt—PA治疗急性心肌梗塞45例临床分析

重组组织型纤溶酶原激活剂（ｒｔ－ＰＡ）已较广泛地应用于临床。１９９５年２月～１９９９年１月，我们应用ｒｔ－ＰＡ治疗４５例急性心肌梗塞（ＡＭＩ）。现报告如下。１资料与方法１．１一般资料同期我院急诊科共收治并确诊ＡＭＩ１３５例，随机分为三组：①Ⅰ组（４５...     

纤溶酶相关蛋白在急性髓性白血病血浆和骨髓中的表达

目的；观察髓性白血病及正常人骨髓单个核细胞及血浆中ｕＰＡ，ｔＰＡ，ＰＡＩ的表达情况并探讨其临床意义。方法：用ＥＬＩＳＡ法测定２０例急性髓性白血病及１５例正常人骨髓单个核细胞及血浆中ｕＰＡ，ｔＰＡ，ＰＡＩ－１，ＰＡＩ－２抗原表达，同时用发色底物法测定血浆中ｔＰＡ，ｕＰＡ和ＰＡＩ－１的活性。结果：骨髓中ｔＰＡ浓度白血病低于正常人，血浆中相反。     

蒿甲醚对小鼠体内日本血吸虫的己糖激酶、磷酸葡萄糖异构酶和磷酸果糖激酶的影响(英文)

目的：研究蒿甲醚（Ａｒｔ）对血吸虫己糖激酶（ＨＫ）、磷酸葡萄糖异构酶（ＧＰＩ）和磷酸果糖激酶（ＰＦＫ）的影响。方法：感染血吸虫小鼠１次ｉｇＡｒｔ１００或３００ｍｇｋｇ－１，并分别于２４ｈ和４８ｈ剖杀取虫。按生成ＮＡＤＰＨ和耗用ＮＡＤＨ的方法测定上述３种酶活力。结果：感染鼠ｉｇ．Ａｒｔ３００ｍｇｋｇ－１后２４ｈ，♀、虫体ＨＫ活力抑制率分别为３３．３％和１３．７％，ＧＰＩ活力则分别抑制１４．７％和１７．５％，４８ｈ后，♀、虫体的ＧＰＩ活力抑制率分别为４６．２％和３２．９％。但Ａｒｔ剂量为１００或３００ｍｇｋｇ－１时，给药后２４ｈ和４８ｈ的♀虫ＰＦＫ抑制率分别为６４．９％和７１％，均明显高于虫的１６．３％和５４．２％。结论：ＰＦＫ可能是Ａｒｔ作用于血吸虫糖酶解途径的靶酶之一。     

尿型纤溶酶原活化素受体在胃癌活检标本中的表达和意义

尿型纤溶酶活化素（Ｕ－ＰＡ）是一种丝氨酸蛋白酶，Ｕ－ＰＡ在体内作用依赖于细胞膜相应受体（Ｕ－ＰＡ－Ｒ）的表达。我们对在内镜下３８例进展期胃癌患者的活检标本检测了Ｕ－ＰＡ－Ｒ和Ｐ５３基因蛋白。其中Ｕ－ＰＡ－Ｒ的阳性率为３４．２％，Ｕ－ＰＡ－Ｒ阳性的胃癌其Ｐ５３基因蛋白均呈阳性表达，另１０例非癌胃粘膜标本作对照，均为阴性。在进展期胃癌中Ｕ－ＰＡ－Ｒ阳性表达胃癌在Ｂｏｒｒｍａｎｎ３，４型者高于Ｂｏｒｒｍａｎｎ１，２型（Ｐ＜０．０５）而与活检标本的病理组织学分型无关。上述结果提示，应用胃镜诊断的进展期胃癌活检标本检测ＵＰＡ－Ｒ可作为胃癌恶性程度及估计预后的一项指标。     

Anistreplase versus alteplase in acute myocardial infarction: comparative effects on left ventricular function, morbidity and 1-day coronary artery patency. The TEAM-3 Investigators.

OBJECTIVES. This double-blind, randomized, multicenter trial was designed to compare the effects of treatment with anistreplase (APSAC) and alteplase (rt-PA) on convalescent left ventricular function, morbidity and coronary artery patency at 1 day in patients with acute myocardial infarction. BACKGROUND. Anistreplase (APSAC) is a new, easily administered thrombolytic agent recently approved for treatment of acute myocardial infarction. Alteplase (rt-PA) is a rapidly acting, relatively fibrin-specific thrombolytic agent that is currently the most widely used agent in the United States. METHODS. Study entry requirements were age less than or equal to 75 years, symptom duration less than or equal to 4 h, ST segment elevation and no contraindications. The two study drugs, APSAC, 30 U/2 to 5 min, and rt-PA, 100 mg/3 h, were each given with aspirin (160 mg/day) and intravenous heparin. Prespecified end points were convalescent left ventricular function (rest/exercise), clinical morbidity and coronary artery patency at 1 day. A total of 325 patients were entered, stratified into groups with anterior (37%) or inferior or other (63%) acute myocardial infarction, randomized to receive APSAC or rt-PA and followed up for 1 month. RESULTS. At entry, patient characteristics in the two groups were balanced. Convalescent ejection fraction at the predischarge study averaged 51.3% in the APSAC group and 54.2% in the rt-PA group (p less than 0.05); at 1 month, ejection fraction averaged 50.2% versus 54.8%, respectively (p less than 0.01). In contrast, ejection fraction showed similar augmentation with exercise at 1 month after APSAC (+4.3% points) and rt-PA (+4.6% points), and exercise times were comparable. Coronary artery patency at 1 day was high and similar in both groups (APSAC 89%, rt-PA 86%). Mortality (APSAC 6.2%, rt-PA 7.9%) and the incidence of other serious clinical events, including stroke, ventricular tachycardia, ventricular fibrillation, heart failure within 1 month, recurrent ischemia and reinfarction were comparable in the two groups; and mechanical interventions were applied with equal frequency. A combined clinical morbidity index was determined and showed a comparable overall outcome for the two treatments. CONCLUSIONS. Convalescent rest ejection fraction was high after both therapies but higher after rt-PA; other clinical outcomes, including exercise function, morbidity index, and 1-day coronary artery patency, were favorable and comparable after APSAC and rt-PA.     

Streptokinase and recombinant tissue plasminogen activator (rt-PA) are equally effective in treating acute myocardial infarction

In recent trials, patients with myocardial infarction who received either recombinant tissue-type plasminogen activator (rt-PA) or streptokinase showed essentially no difference in the amount of myocardial salvage, in mortality reduction, or in the incidence of bleeding complications. These findings thus failed to fulfill the expectation that rt-PA would be twice as effective as streptokinase as a thrombolytic agent. The basis for this mistaken prediction was an unfortunate overemphasis on an inadequate surrogate endpoint, namely, the patency or reperfusion rate at 90 minutes after the start of therapy. Using the 90-minute patency or reperfusion rate as an endpoint has several serious limitations. First, it is an observation made at only one point in time during a dynamic process that may change even during the infusion proper. Second, a single view at 90 minutes completely disregards the possibility of subsequent reocclusion which often occurs within 1 hour after treatment. Third, an image at 90 minutes is more a reflection of the speed of thrombolysis than of whether lysis will eventually occur; the pace of clot lysis depends on both the agent used and the age of the thrombus. Fourth, lysis at 90 minutes is of minimal relevance for myocardial salvage unless observed within the time frame when infarction size can be limited significantly, which is generally less than 4 hours between symptom onset and the time that reperfusion is accomplished. Fifth, a stable state of vessel patency is meaningful for mortality reduction even if stabilization occurs after completion of the infarction. Such "late," but lasting, patency is a critical component of the "open vessel" principle and explains, at least in part, the survival benefit that accrues to patients treated even 24 hours after the onset of symptoms. There is currently no evidence that rt-PA has a more beneficial effect on survival or function than does streptokinase or any other plasminogen activator used in treating acute myocardial infarction; nor is there any evidence that patients who receive rt-PA therapy show a decreased incidence of bleeding complications compared with those who receive streptokinase, despite the relative fibrinogen-sparing attribute of rt-PA. Given the poor predictive value of the 90-minute angiogram for ultimate clinical advantage of one agent over another, studies that are limited to this endpoint are of marginal use in evaluating treatment regimens used in mortality studies. The best evidence to date indicates that streptokinase and rt-PA are of equivalent value for survival after acute myocardial infarction, a conclusion that can be justifiably challenged only with a valid mortality study.     

注射用重组瑞替普酶治疗急性心肌梗死的疗效评价

目的对比观察瑞替普酶(reteplase rPA)与重组组织型纤溶酶原激活剂(rt-PA)用于急性心肌梗死(AMI)溶栓治疗的效果及安全性。方法自2001年11月~2002年5月,共26例AMI患者随机接受rPA或rt-PA溶栓治疗,观察溶栓再通率、急性期死亡率、并发症及不良反应发生率。结果溶栓后2h再通率rPA为92.86%,rt-PA组为75%(P>0.05),90min rPA组3例行冠状动脉造影显示全部再通,rt-PA组3例冠状动造影显示仅1例再通,35d rPA组病死率为14.29%,rt-PA组病死率8.33%(P>0.05),两组各有1例患者发生冠状动脉再闭塞,rt-PA组1例患者发生心力衰竭(P>0.05)。结论rPA为国人治疗AMI安全、有效的溶栓药物。     

重组组织型纤溶酶原激活剂静脉溶栓治疗急性心肌梗死23例临床分析

目的观察重组组织型纤溶酶原激活剂(recombinant tissue—type plasminogen activator，rt—PA)静脉溶栓治疗急性心肌梗死的疗效，探讨溶栓时间窗。方法23例心肌梗死患应用rt—PA静脉溶栓治疗，通过观察临床症状、心电图、心肌酶谱的变化，判断冠状动脉再通率，并观察出血的发生率及严重程度。结果23例患溶栓后冠状动脉再通17例，其中，发病6小时内13例溶栓冠状动脉再通11例，发病6～12小时内10例溶栓冠状动脉再通6例；1例再通24小时发生再梗死；2例出现牙龈出血；1例出现皮下出血。结论rt—PA静脉溶栓治疗心肌梗死在发病6小时内应用疗效显，发病6～12小时应用仍然有效。     

Improved thrombolysis in acute myocardial infarction with front-loaded administration of alteplase: results of the rt-PA-APSAC patency study (TAPS)

Thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) and anisoylated plasminogen streptokinase activator (APSAC) in myocardial infarction has been proved to reduce mortality. A new front-loaded infusion regimen of 100 mg of rt-PA with an initial bolus dose of 15 mg followed by an infusion of 50 mg over 30 min and 35 mg over 60 min has been reported to yield higher patency rates than those achieved with standard regimens of thrombolytic treatment. The effects of this front-loaded administration of rt-PA versus those obtained with APSAC on early patency and reocclusion of infarct-related coronary arteries were investigated in a randomized multicenter trial in 421 patients with acute myocardial infarction. Coronary angiography 90 min after the start of treatment revealed a patent infarct-related artery (Thrombolysis in Myocardial Infarction [TIMI] grade 2 or 3) in 84.4% of 199 patients given rt-PA versus 70.3% of 202 patients given APSAC (p = 0.0007). Early reocclusion within 24 to 48 h was documented in 10.3% of 174 patients given rt-PA versus 2.5% of 163 patients given APSAC. Late reocclusion within 21 days was observed in 2.6% of 152 patients given rt-PA versus 6.3% of 159 patients given APSAC. There were 5 in-hospital deaths (2.4%) in the rt-PA group and 17 deaths (8.1%) in the APSAC group (p = 0.0095). The reinfarction rate was 3.8% and 4.8%, respectively. Peak serum creatine kinase and left ventricular ejection fraction at follow-up angiography were essentially identical in both treatment groups. There were more bleeding complications after APSAC (45% vs. 31%, p = 0.0019).(ABSTRACT TRUNCATED AT 250 WORDS)     

ECG evidence of limited myocardial infarction following coronary occlusion treated by early intravenous rt-PA infusion

Serial 12-lead surface electrocardiograms (ECGs) were analysed in 110 patients with first evolving myocardial infarction entered in a double-blind placebo-controlled trial of intravenous rt-PA within 2.5 h (mean 1.9 +/- 0.5 (SD)) of pain onset. ECG analysis was performed by two 'blinded' analysts. QRS scoring (by the modified Selvester method) was used as an index of myocardial necrosis. Patient results were analysed according to infarct location. There was no difference between the two treatment groups in ST-segment elevation or QRS score at entry or up to 24 h after symptom onset. However from 24 h, QRS score was lower in patients with anterior infarction given rt-PA than in those given placebo: 5.4 +/- 2.8 vs 7.7 +/- 4.1 (P = 0.02) at 48 h; 4.7 +/- 3.2 vs 8.0 +/- 4.0 (P = 0.01) at 4-10 days; and 4.6 +/- 3.9 vs 7.5 +/- 3.9 (P = 0.01) at 21 days. For patients with inferior infarction, rt-PA treatment also resulted in a lower QRS score although this was not significantly different from the score of the placebo group (P = 0.07). Comparison of QRS scores with ejection fraction measured from the contrast ventriculogram taken at 21 days showed a moderate correlation (r = 0.46) in patients with anterior infarction but a poor correlation in patients with inferior infarction. These ECG results indicate that in evolving anterior myocardial infarction, there is limitation of infarct size from early rt-PA infusion.     

Combined tissue-type plasminogen activator and prostacyclin therapy for acute myocardial infarction. Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) 4 Study Group

Current limitations of recombinant tissue-type plasminogen activator (rt-PA) therapy for acute myocardial infarction include failure to achieve recanalization in 25% of patients, reocclusion and reperfusion injury. Iloprost, a stable analogue of prostacyclin (PGI2), has been demonstrated to facilitate thrombolysis and reduce myocardial stunning in experimental models. To evaluate combined therapy, rt-PA (100 mg 3 h) and Iloprost (2 ng/kg per min for 48 h) were administered to 25 patients and then rt-PA alone (same dose) was given to an additional 25 patients with evolving myocardial infarction. At 90 min after drug administration, infarct-related vessel patency was observed in 11 (44%) of 25 who received rt-PA plus Iloprost compared with 15 (60%) of 25 who received rt-PA alone (p = 0.26). At 1 week, reocclusion had occurred in 3 (14%) of 21 patients who received combined therapy compared with 6 (26%) of 23 patients treated with rt-PA alone (p = 0.46). Ejection fraction increased significantly from baseline to 7 days for rt-PA alone whereas it decreased with combined therapy (rt-PA alone whereas it decreased with combined therapy (rt-PA alone: 47.3 +/- 11.5% at baseline to 50.4 +/- 9.8% at 7 days; rt-PA plus Iloprost: 51.3 +/- 10.1% at baseline to 49.0 +/- 9.4% at 7 days; difference between groups p = 0.05). At 4 h after therapy, fibrinogen decreased 33% for rt-PA plus Iloprost compared with a 52% for rt-PA alone (p = 0.001). Fibrinogen degradation products increased 60% more for rt-PA alone than for rt-PA plus Ilprost. Thus, the combination of rt-PA plus Iloprost at the doses employed did not improve immediate or follow-up coronary artery patency or left ventricular functional recovery compared with that achieved with rt-PA alone.     

Intravenous recombinant tissue plasminogen activator (rt-PA) and urokinase in acute myocardial infarction: results of the German Activator Urokinase Study (GAUS)

The effects of recombinant tissue plasminogen activator (rt-PA) and urokinase on patency and early reocclusion of infarct-related coronary arteries were investigated in a single blind, randomized multicenter trial in 246 patients with acute myocardial infarction of less than 6 h duration. Both 70 mg of single chain rt-PA with an initial bolus of 10 mg and 3 million units of urokinase with an initial bolus of 1.5 million units were given intravenously over 90 min. The first angiographic study at the end of the infusion revealed a patent infarct-related artery (Thrombolysis in Myocardial Infarction trial [TIMI] grade 2 or 3) in 69.4% of 121 patients given rt-PA versus 65.8% of 117 patients given urokinase (p = NS). Among patients treated within 3 h from symptom onset a patent infarct-related artery was found in 63.9% of 72 patients given rt-PA versus 70% of 70 patients given urokinase (p = NS). There were five cardiac deaths in each group and one fatal intracranial hemorrhage in the rt-PA group. The in-hospital reinfarction rate was 8.9% versus 13.2% for patients treated with rt-PA and urokinase, respectively. There was no difference in left ventricular function at baseline and follow-up catheterization studies. Both drugs were well tolerated and there was no significant difference in cardiovascular or bleeding complications between the two groups. It is concluded that rt-PA and urokinase in the dosages used provide similar efficacy and safety in the treatment of acute myocardial infarction. Reocclusion during the first 24 h may be less frequent after urokinase treatment.     

rt-PA治疗急性ST段抬高心肌梗死的疗效

目的：探讨急性ST段抬高心肌梗死（STEMI）患者应用瑞替普酶（rt-PA）静脉内溶栓的临床效果。方法：94例STEMI患者给予rt-PA静脉内溶栓,分析其溶栓再通率、再灌注心律失常情况、不良反应发生率和急性期病死率。结果：应用rt-PA静脉内溶栓的患者再通率88．3％;牙龈出血、恶心、呕吐等并发症发生率9．5％,无严重的出血并发症（如脑出血、消化道大出血等）;室性早搏等再灌注心律失常发生率73．4％。结论：应用rt-PA静脉内溶栓治疗AMI,再通率较高,出血并发症少。