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。     

Early and late exercise capacity after acute myocardial infarction treated with recombinant tissue-plasminogen activator

Thrombolytic therapy salvages jeopardized myocardium and preservesleft ventricular function. Therefore, a beneficial effect onexercise tolerance and haemodynamic adaptation to exercise canbe anticipated. In the present study the results of bicycleexercise tests, performed at 10 to 14 days and at more than1 year after infarction, were compared between patients randomizeddouble blindly to recombinant tissue plasminogen activator (rt-PA)or placebo. At 2 weeks, the maximal heart rate (140 vs 130 beats.min^–1 P=0.017), systolic blood pressure (169 vs 161 mmHg,P=0.018) and pressure-rate product (22907 vs 20865 beats. min^-1mmHg,P=0.0025) were higher in rt-PA treated patients (n=145) thanin controls (n=142). At a mean follow-up of 16 months, rt-PApatients (n=126) performed a higher total and peak work load(733 vs 600 Watts. min, P=0.027 and 133 vs 100 Watts, P=-0.036,respectively) than control patients (n=122). During both exercisetests the incidence of clinical or electrocardiographic signsof ischaemia was similar. Multiple regression analysis indicatedthat age and end-systolic volume were predictors of peak pressure-rateproduct at 2 weeks (R²=0.11, P=0.0001). Age, sex and left ventricularejection fraction at discharge were independent predictors ofpeak work load at 2 weeks (R²=0.32, P=0.0001) and the squareroot of peak work load at 16 months (R²=0.39, P=0.001). Thesefindings suggest that an improved left ventricular functionin the thrombolysis group plays a role in the better exercisecapacity observed in rt-PA treated patients.     

Low level of tissue plasminogen activator activity in non-diabetic patients with a first myocardial infarction

OBJECTIVE: To explore the role of tissue plasminogen activator (tPA) activity and plasminogen activator inhibitor type 1 (PAI-1) in survivors of a first myocardial infarction (MI). Insulin and proinsulin were analysed as potential risk factors. DESIGN: Case-control study in northern Sweden. SUBJECTS: A total of 115 patients under 65 years of age with a first MI were enrolled and recalled for further examination 3 months later. Twenty-seven patients were excluded, 17 with known diabetes and 10 who did not come to the follow-up, giving a final number of 88 patients, 73 men and 15 women. Patients were age- and sex-matched with control subjects drawn from the local cohort in the MONICA population survey 1994. MAIN OUTCOME MEASURES: We compared MI patients and controls using univariate and multiple regression analyses including odds ratios (OR). RESULTS: PAI-1 activity, fibrinogen, postload insulin and -proinsulin were significantly higher and tPA activity significantly lower in MI patients in the univariate analysis. In a multiple regression analysis, including also age, sex and cardiovascular risk factors, these parameters were divided in quartiles. The lowest quartile of tPA activity was significantly associated with MI (OR = 19.1; CI 3.0-123) together with the highest quartiles of fibrinogen (OR = 25; CI 5.2-120) but other variables were not. CONCLUSION: Low tPA activity, i.e. low fibrinolytic activity, characterized nondiabetic subjects after a first MI which is not explained by concomitant disturbances in metabolic and anthropometric variables.     

低剂量重组组织型纤溶酶原激活剂与尿激酶联合溶栓治疗急性脑梗死

目的观察联合应用重组组织型纤溶酶原激活剂（rt—PA）和尿激酶治疗急性脑梗死的有效性和安全性。方法选择发病〈6h的急性脑梗死患者81例,分为联合溶栓组（20例）、单用rt—PA组（22例）、单用尿激酶组（18例）及对照组（21例）。联合溶栓组静脉给予rt—PA20mg,尿激酶30万-50万IU;单用rt—PA组静脉给予rt—PA0．9mg／kg;单用尿激酶组静脉给予尿激酶1万～2万IU／kg（体质量超过75kg者按75kg给药）,最大剂量150万IU;未溶栓病例为对照组。主要疗效指标是观察治疗前与发病后4周的神经功能缺损评分（NIHSS）变化,以溶栓后出血转化、24h内再梗死及死亡等作为安全指标。结果联合溶栓组、单用rt—PA组、单用尿激酶组及对照组的观察结果为：①NIHSS评分治疗前分别为18．1±3．6、17．9±3．6、18．0±3．4、17．3±4．0,治疗后分别为9．1±5．6、8．8±5．5、9．6±5．2、14．1±4．6,符组治疗前、后比较,差异均有统计学意义（P〈0．01）,3个溶栓组与对照组比较差异均有统计学意义（P〈0．01）;3个溶栓组比较,差异无统计学意义。②4组治疗后总有效率分别为85．0％（17／20）、86．4％（19／22）、83．3％（15／18）和42．9％（9／21）,与对照组比较差异有统计学意义（P〈0．05）;各溶栓组间比较,差异无统计学意义（P〉0．05）。③联合溶栓组溶栓后24h内再发脑梗死1例,出血转化1例;单用rt—PA组出血转化3例;单用尿激酶组再梗死1例,出血转化有2例,其中死亡1例。对照组再梗死1例,死亡1例。结论与单用rt—PA和单用尿激酶比较,联合低剂量rt-PA和尿激酶溶栓治疗急性脑梗死同样安全、有效,相对rt—PA价格便宜,值得推广应用。     

小剂量重组织型纤溶酶原激活剂与尿激酶、重组链激酶溶栓治疗急性心肌梗死的临床对比分析

目的观察小剂量重组织型纤溶酶原激活剂（rt—PA）、尿激酶（UK）和重组链激酶（r—sK）治疗急性心肌梗死的疗效和安全性。方法114例急性心肌梗死患者随机分为rt—PA组38例，UK组37例，r—SK组39例。分别应用纤溶酶原激活剂50mg、尿激酶150万U、链激酶150万U静脉输入。结果rt—PA组、UK组、r—sK组临床血管再通率分别为84．21％、51．35％、69．23％，三者之间疗效比较P〈0．05。3组溶栓后不良反应、5周病死率比较P〉0．05，差异无显著性。结论rt—PA治疗急性心肌梗死的疗效明显优于UK和r—SK，而r—SK的疗效优于UK。溶栓后不良反应、5周病死率比较差异无显著性。     

重组组织型纤溶酶原激活剂静脉溶栓治疗急性心肌梗死后的QT离散度变化

３６例急性心肌梗死患者接受重组组织型纤溶酶原激活剂（ｒｔ－ＰＡ）静脉溶栓治疗。其中有效２１例，无效１３例。有效组在溶栓后２小时、８小时、２４小时的ＱＴｃ离散度（ＱＴｃｄ）与溶栓前相比较，有下降趋势，但未达到统计显著性。无效组在溶栓后２小时、８小时、２４小时的ＱＴｃｄ与溶栓前相比较，有显著性延长（Ｐ＜０００１）。有效组与无效组相比，溶栓后２小时、８小时、２４小时之ＱＴｃｄ，差异有显著性（Ｐ＜０００１）。     

重组组织型纤溶酶原激活剂静脉溶栓治疗急性脑梗死的临床研究

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(ACI)患者的疗效及安全性。方法:将发病在4.5 h内ACI患者139例,且均符合静脉溶栓适应证,按入院顺序分为rt-PA组(61例)和对照组(ACI)(78例),分别给予rt-PA静脉溶栓和奥扎格雷钠治疗。采用NIHSS及mRS评分比较2组患者治疗后24 h、7 d、90 d的疗效及安全性。结果:rt-PA组治疗后7 d,NIHSS评分较对照组改善更显著。rt-PA组90 d mRS评分优于对照组。2组病死率、症状性颅内出血发生率无统计学差异。结论:ACI患者4.5 h内给予rt-PA静脉溶栓,疗效优于奥扎格雷钠,且较为安全。     

A depression of active tissue plasminogen activator in plasma characterizes patients with unstable angina pectoris who develop myocardial infarction

The balance between the coagulation system generating fibrin and its subsequent removal by the fibrinolytic system determines the fate of fibrin deposited in the vascular system. In a prospective study, selected haemostatic variables assessing this balance were determined in plasma samples from 20 consecutive patients admitted with unstable angina pectoris. Over a follow-up period of 6 years, eight patients developed myocardial infarction, whereas 12 patients did not. There was no significant difference between the two groups in the median plasma concentrations of thrombin-antithrombin III complexes reflecting the coagulant activity. The infarction group was characterized by a significantly lower median activity of tissue plasminogen activator in plasma euglobulins (P less than 0.05), a higher median concentration of tissue plasminogen activator antigen in plasma (P less than 0.05) and a tendency to higher plasma levels of antigenic and functional plasminogen activator inhibition. In all patients, the activities of tissue plasminogen activator inhibitor and of tissue plasminogen activator were significantly associated (rs = -0.4811, P less than 0.05). We conclude that a depressed fibrinolytic capacity attributable to a low tissue plasminogen activator activity is of pathogenetic importance for the development of myocardial infarction in patients with unstable angina pectoris.     

重组组织型纤溶酶原激活剂静脉溶栓治疗急性心肌梗死20例分析

目的 :探讨重组组织型纤溶酶原激活剂 (rt PA)静脉溶栓治疗急性心肌梗死 (AMI)的疗效及安全性。方法 :选择 2 0例AMI患者应用rt PA静脉溶栓治疗 ,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。结果 :① 2 0例AMI患者 ,冠状动脉再通 12例 ,再通率 6 0 %,其中发病 6h以内溶栓再通率 87.5 %(7/ 8) ,发病 6～ 2 4h溶栓再通率 4 1.7%(5 / 12 ) ,两者相比差异有显著性意义 (P <0 .0 5 )。②≤ 6 5岁患者的血管再通率与不良反应发生率与 >6 5岁组相比差异无显著性意义 (P >0 .0 5 )。结论 :rt PA静脉溶栓治疗AMI是一种安全、有效的方法 ,宜提倡急诊室溶栓。 >6 5岁患者行静脉溶栓治疗是安全可行的 ,但要根据患者的具体情况而定。     

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。     

尿激酶与组织型纤溶酶原激活剂静脉溶栓治疗急性心肌梗塞的对比研究

为比较尿激酶（UK）及组织型纤溶酶原激活剂（t-PA）静脉溶栓辅以阿司匹林及肝素对急性心肌梗塞的效果及其副作用。对急性心肌梗塞患者发病6h内者，42例给予静脉UK15例静脉内t-PA溶栓辅以静脉肝素及阿司匹林治疗。结果表明，t-PA组、UK组临床血管再通率分别为86．7％与57．1％（P＜0．05），前者消化道与呼吸道出血并发症为13．3％，而后者为0（P＜0．05）。本研究提示静脉t-PA溶栓血管再通率显著高于静脉UK，但出血合并症的发生t-PA组显著高于UK组。     

Accelerated plasminogen activator inhibitor may prevent late restenosis after coronary stenting in acute myocardial infarction

BACKGROUND: Although acceleration of plasma plasminogen activator inhibitor-1 (PA-1) level after emergent coronary angioplasty in acute myocardial infarction (AMI) has been documented, its pathophysiologic role is still unknown. HYPOTHESIS: This study was designed to elucidate the role of PAI-1 in the development of restenosis after primary coronary stenting in AMI. METHODS: We selected for this study 66 patients with AMI, who underwent primary coronary stenting for infarct-related coronary artery lesions in an emergent situation. In all patients, plasma PAI-1 level was measured at admission, and at 3 h, 24 h, 48 h, and 1 month after coronary stenting. RESULTS: At admission, the PAI-1 level was equivalent in 24 patients who experienced restenosis and in 42 patients without restenosis (28 +/- 4 vs. 29 +/- 4 ng/ml). In patients with restenosis, the levels did not change during the course after coronary stenting. In patients without restenosis, however, the level significantly increased at 3 h (48 +/- 9 ng/ml, p < 0.001), 24 h (42 +/- 9, p < 0.01), and 48 h (38 +/- 7, p < 0.05) after coronary stenting, and was restored to the level equivalent to that at admission (27 +/- 2 ng/ml) I month aftercoronary stenting. The PA-1 level at 3 h after coronary stenting in patients without restenosis was significantly higher (p < 0.05) than the level (33 +/- 6 ng/ml) in patients with restenosis. Multiple logistic regression analysis indicated that the PAI-1 level 3 h after coronary stenting was an independent predictor of restenosis (Wald chi2 = 3.826, p = 0.019, odds ratio 0.921, 95% confidence interval 0.866-0.961). CONCLUSION: Accelerated PAI-1 after coronary stenting in patients with AMI may protect against the development of late restenosis.     

Late (one month) reversible ischaemia after primary coronary occlusion treated with recombinant tissue plasminogen activator (rTPA)

Abstract The incidence of reversible ischaemia was assessed four weeks after primary coronary occlusion in 36 patients who had not required earlier revascularisation after randomisation to receive rTPA (n= 19) or placebo (n= 17). Coronary arteriography was performed at three weeks and thallium scintigraphy with dynamic stress testing at four weeks. Patients were followed for one year without planned intervention in the absence of symptoms. Managing physicians remained blinded to thrombolytic therapy. Patency rate of the infarct related artery at three weeks was greater after rTPA (rTPA 16, placebo 9; p= 0.04). Reversible perfusion defects within infarct related artery territory occurred with similar frequency in both treatment groups (rTPA 7, placebo 8). Multivessel disease was frequent (rTPA 11, placebo 12) but associated with a low incidence of reversible perfusion defects outside infarct related artery territory (rTPA 3, placebo 2). Thallium scintigraphy identified six of seven patients requiring subsequent revascularisation (sensitivity 86%, specificity 59%, negative predictive value 94%). Dynamic stress testing was positive for reversible ischaemia in 28% (rTPA 6, placebo 4) and identified two patients requiring revascularisation (sensitivity 29%, specificity 72%, negative predictive value 81%). The greater patency rate achieved with rTPA at three weeks after primary coronary occlusion was not associated with a significantly greater incidence of reversible perfusion defects at four weeks in patients who had not required prior revascularisation. The absence of reversible perfusion defects at four weeks was associated with a low incidence of revascularisation procedures during one year follow-up.     

重组组织型纤溶酶原激活剂联合尿激酶治疗急性脑梗死的临床观察

目的观察低剂量重组组织型纤溶酶原激活剂(rt-PA)联合尿激酶静脉溶栓治疗急性脑梗死的远期疗效和安全性。方法选择急性脑梗死患者161例,分为4组:联合溶栓组44例,给予静脉rt-PA尿激酶;rt-PA组37例,尿激酶组32例,对照组48例。观察治疗前及治疗后90 d美国国立卫生研究所卒中量表(NIHSS)评分,同时观察再梗死率、脑出血率及病死率。结果与治疗前比较,4组治疗后90 d NIHSS评分差异均有统计学意义(P<0.01)。3个溶栓组与对照组在90 d有效率及疗效满意率差异均有统计学意义(P<0.01);3个溶栓组90 d有效率及疗效满意率差异无统计学意义(P>0.05)。联合溶栓组与rt-PA组和尿激酶组脑出血率比较差异均有统计学意义(2.3%υs 18.9%υs 18.7%,P<0.05)。结论 rt-PA联合尿激酶治疗急性脑梗死远期疗效和单用rt-PA、单用尿激酶相当,但脑出血率降低,因此该治疗方法是安全有效的,值得推广应用。     

急性脑梗死患者重组组织型纤溶酶原激活物静脉溶栓后脑出血

重组组织型纤溶酶原激活物(recombinant tissue plasminogen activator,rtPA)静脉溶栓是急性缺血性卒中最有效的治疗手段,其最严重的并发症为有症状脑出血,文献撒道其总体发生率为6%,与血管损伤和通透性增加有关.某些临床特征、影像学和实验室检查可预测脑出血并发症风险.溶栓治疗后发生脑出血并发症的患者病死率和致残率极高,预后很差.文章对溶栓后脑出血的分型、发生率、预测因素和预后进行了综述.     

Protection by α2-macroglobulin of tissue plasminogen activator against inhibition by plasminogen activator inhibitor-1

Tissue plasminogen activator (tPA) is widely used in the treatment of acute myocardial infarction (MI). However, its thrombolytic efficacy does not correlate with the dose administered. The interactions between tPA, α2-macroglobulin (α2-M), and plasminogen activator inhibitor-1 (PAI-1) were investigated both in vitro and in patients undergoing tPA therapy for MI in an attempt to identify variables that might affect the clinical efficacy of tPA.
Purified α2-M (5.4 mg/ml) protected 16.0% or 22.4% of tPA (12.5 IU/ml) activity from inhibition by PAI-1 at 4 or 8 IU/ml in vitro . Of nine patients treated with 5–20 mega IU of tPA for MI, the plasma activity of tPA remained increased for 15–30 min after the cessation of infusion in eight; the patient who failed to exhibit a persistent increase in tPA activity had a low plasma concentration of α2-M. Total tPA activity, derived from the area under the activity-versus-time curve (AUC), showed a significant inverse correlation with the ratio of the plasma PAI-1 activity to the plasma α2-M concentration. Total tPA activity did not correlate with plasma PAI-1 activity or plasma α2-M concentration alone. Results suggest that α2-M, by binding to tPA, protects the latter against inhibition by PAI-1.     

急性心肌梗死PCI中Percusurge远端保护装置对P-选择素和纤溶活性的影响

目的探讨Percusurge远端保护装置（DPD）在急性心肌梗死（AM I）PC I中对P-选择素（Ps）、纤溶酶原激活剂（t-PA）、纤溶酶原激活剂抑制物-1（PAI-1）的影响及作用机制。方法接受急诊PC I治疗的AM I患者72例,DPD组39例,对照组33例,经股静脉将6F右冠状动脉造影导管置入冠状静脉窦于PTCA前、DPD后即刻、0.5、2、6 h采血分别检测血中Ps,t-PA,PAI-1水平。结果①DPD组术后6 h Ps含量降低（P<0.05）与对照组比较在术后6 h有显著性差异（P<0.05）;术后即刻至术后6 h血浆t-PA活性降低（P<0.05）与PAI-1含量升高（P<0.05）,与对照组比较无统计学差异。②两组住院期间心血管病事件发生率无明显统计学差异。结论Percusurge远端保护装置能有效保护远端血管,减轻PTCA术后血小板的激活,减少再灌流后无复流的发生。     

脑梗死急性期血浆组织型纤溶酶原激活物对其预后的影响

目的探讨脑梗死急性期血浆中组织型纤溶酶原激活物（t—PA）水平对脑梗死预后的评估价值。方法采用前瞻性设计，将120例急性脑梗死患者分为t—PA正常组（〉1．3IU／ml）69例和t—PA降低组（≤1．3IU／ml）51例，对两组患者进行生存分析比较。在发病72h内检测血浆t—PA水平，随访1年，将死亡及再发缺血性血管病记录为终点事件。采用多元回归分析，分析t-PA、高血压、糖尿病、冠心病、高血脂、年龄、吸烟、饮酒等因素对终点事件的影响。结果①t-PA降低组患者较t-PA正常组患者终点事件发生率显著增加（28．9％，11．7％；P=0．007，log-rank检验）；②多变量回归分析显示，t-PA降低（OR=3．966；95％CI：1．753-13．285；P=0．039）、吸烟（OR=5．233；95％CI：1．991～16．227；P=0．035）及糖尿病（OR=4786；95％CI：1．591—16．709；P=0．033）与终点事件独立相关。结论脑梗死急性期t-PA降低可能是脑梗死发病1年内死亡和再发缺血性血管病的独立危险因素。     

国人小剂量与快速常规剂量rt-PA治疗急性心肌梗死的疗效与安全性比较

目的：评价重组组织型纤溶酶原激活剂(rt—PA)快速给药对国人急性心肌梗死(AMl)溶栓治疗的疗效及安全性，并与小剂量rt—PA的疗效进行对比。方法：快速常规剂量组(R组)75例AMI病人在阿司匹林和肝素治疗后接受20mg rt—PA一次弹丸注射，随后80mg半小时内快速滴入，尽快行急诊冠状动脉造影响术。小剂量治疗组(S组)32例AMI病人在阿斯匹林和肝家治疗基础上接受8mg rt—PA一次弹丸注射，继之42mg在90分钟内滴入，并进行冠状动脉造影。以用药后冠状动脉造影显示梗死相关动脉(1RA)TIMI血流分级作为主要终点评价疗效。结果：107例冠状动脉造影的冠状动脉血流通畅率(TIMt和I级)：R组显高于S组(88％、75％，P＜0．01)，达到了IMl3级血流R组亦高于S组(62％、47％，P＜0．01)，左室射血分数：R组明显高于S组(P＝0．05)，出血发生率：两组差异无显性。结论：快速常规剂量rt—PA对国人AMI病人是有效和安全的。其冠状动脉再通率明显高于小剂量rt—PA治疗。