Failure of thrombolysis by streptokinase: detection with a simple electrocardiographic method

OBJECTIVE—To determine whether simple, readily applicable ECG criteria will allow early prediction of inadequate (< TIMI 3) flow in the infarct related vessel in patients receiving thrombolytic treatment for acute myocardial infarction; and to determine the success of streptokinase in achieving adequate antegrade flow in the infarct related vessel two hours after starting treatment.
DESIGN—Cohort study.
SETTING—Regional cardiothoracic unit.
PATIENTS—100 sequential patients with acute myocardial infarction.
INTERVENTIONS—Coronary angiography two hours after the initiation of thrombolytic treatment, proceeding to rescue angioplasty for inadequate flow in the infarct related vessel where appropriate.
MAIN OUTCOME MEASURES—Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of six ECG criteria for the detection of inadequate antegrade flow in the infarct related vessel.
RESULTS—The ECG test that performed best as a positive test for < TIMI 3 flow in the infarct related vessel was < 50% resolution of the ST segment elevation in the worst lead and no accelerated idioventricular rhythm. This had a sensitivity of 81%, specificity of 88%, positive predictive value of 87%, negative predictive value of 83%, and overall accuracy of 85%.
CONCLUSIONS—Sensitive, specific, and simple ECG criteria are defined for diagnosing failure of thrombolytic treatment with streptokinase. These allow the early detection of patients at high risk of further adverse events from a persistently occluded vessel. They may be used without recourse to sophisticated equipment or complex analyses. Such patients can then be considered for alternative treatments or enrolment into appropriate research protocols.


Keywords: myocardial infarction; thrombolysis; streptokinase     

An angiographic study of intracoronary streptokinase versus intravenous tissue plasminogen activator after failed coronary thrombolysis with intravenous streptokinase

Objective The medical treatment of failed intravenous streptokinase in patients with acute transmural myocardial infarction using angiographic endpoints.Design Prospective open angiographic comparison of intracoronary streptokinase with intravenous tissue plasminogen activator. Setting: Single center study in a tertiary institution.Subjects Eighty-five patients with acute myocardial infarction within 4 hours after symptom onset. Treatment regimens: The subjects received 1.5 million U intravenous streptokinase. Coronary angiography within 48 hours (median 19 hours) showed infarct-related vessel patency in 65 patients (76%). In the catheterization laboratory the 20 patients (24%) with failed intravenous streptokinase received repeat thrombolysis immediately after angiography. The first 10 patients with failed intravenous streptokinase received intracoronary streptokinase at a dose of 4000 U/min in the occluded infarctrelated artery for a maximum of 1 hour. The subsequent 10 patients received high-dose front-loaded intravenous tissue plasminogen activator (100 mg in 1 hour).Results In none of the patients receiving repeat streptokinase was reperfusion obtained. In 6 of 10 (60%) of the patients receiving tissue plasminogen activator, reperfusion was seen within 60 minutes (p < 0.005 vs. intracoronary streptokinase). One patient (5%) died and two refused follow-up angiography. Seventeen (88%) patients underwent angiography 3 months later according to the protocol. Two patients showed a persistently reperfused infarct-related artery, three reoccluded, four spontaneously reperfused, and eight had a persistently occluded infarct-related artery. The left ventricular ejection fraction was slightly higher at 3 months, and there were no differences between the patients with open vessels (increase + 7.7 ± 5.8%) and those with persistently occluded vessels (increase +5.8 ± 6.8%)Conclusions Repeat thrombolysis after failed intravenous streptokinase can be achieved with front-loaded intravenous tissue plasminogen activator but not with intracoronary streptokinase. Although patient numbers are small and repeat thrombolysis was performed rather late, this study leads the way to affordable optimization of thrombolysis, which needs large-scale testing.     

Immediate PTCA after successful thrombolysis with intracoronary streptokinase, three years follow-up: A matched pair analysis of the effect of PTCA in the randomized multicentre trial of intracoronary streptokinase, conducted by the Interuniversity Cardiology Institute of the Netherlands

Immediate PTCA following thrombolysis with streptokinase wasperformed in 46 out of 533 patients enrolled in a multicentrerandomized trial of early reperfusion in patients with acutemyocardial infarction. Additional effects of PTCA in patientswith a residual diameter stenosis in the infarct-related coronaryartery of 70% or more after thrombolysis were compared withsuccessful thrombolysis alone in a matched pair analysis. Thirtysix pairs of patients were formed identical with respect tothe infarct related coronary artery, presence or absence ofprevious myocardial infarction, total ST segment elevation onthe ECG at admission to the trial, and delay between onset ofsymptoms and hospital admission. PTCA after thrombolysis didnot lead to additional limitation of infarct size, nor to furtherpreservation of left ventricular function. Infarction rate duringthe three-year follow-up was 14% after PTCA versus 30% afterthrombolysis alone (P = 0.05). Similarly, patients had lessangina or heart failure after PTCA, since on average 128 outof 156 weeks follow-up were symptom free, while this was only102 weeks after thrombolysis alone (P = 0.03). Immediate PTCAafter thrombolysis with intracoronary streptokinase seems toprevent recurrent ischemia and reinfarction. Further studiesshould address the proper indication and timing of PTCA afterthrombolysis.     

Local beta-adrenergic blockade does not reduce infarct size after coronary occlusion and reperfusion: A study of coronary venous retroinfusion of metoprolol

Summary Previous studies have demonstrated pronounced ischemic zone myocardial concentrations of metoprolol following coronary venous retroinfusion in pigs with coronary artery ligation. The effect of coronary venous retroinfusion of metoprolol on myocardial infarct size was studied in 16 pentobarbital-anesthetized open-chest pigs undergoing 60-minute occlusion of the left anterior descending coronary artery followed by 3 hours of reperfusion. Pigs in the experimental group (n=8) were given 0.4 mg/kg (1.0 mg/ml) of metoprolol via the anterior interventricular vein over a period of 5 minutes, beginning immediately after coronary occlusion followed by 0.2 mg/kg/hr intravenously. Control pigs (n=8) received the same volume of saline as the treated group. The risk area and the necrotic area were assessed by monastral blue dye and triphenyl tetrazolium chloride staining, respectively. Metoprolol did not influence hemodynamics. Plasma concentrations of metoprolol were within therapeutic levels. The administration of the beta-blocker resulted in a trend toward reduced norepinephrine concentrations, both in the aorta and coronary vein after coronary occlusion, but it did not prevent norepinephrine overflow following reperfusion. Infarct size expressed as a percentage of the risk area was 77±11% in the control group and 75±12% (mean ± SD; NS) in the treated group. Thus, metoprolol retroinfusion did not reduce infarct size and did not prevent catecholamine overflow after reperfusion. It is concluded that the beneficial effects of metoprolol in acute infarction are probably unrelated to local beta-adrenergic blockade, at least in the pig, an animal with a paucity of coronary collateral blood flow.     

链激酶,尿激酶静脉溶栓对凝血和纤溶系统的影响

尿激酶（ＵＫ）和链激酶（ＳＫ）同属第一代溶栓剂，二者均无“纤维蛋白选择性”，本研究目的在于比较ＳＫ和ＵＫ对凝血和纤溶系统的影响及其与临床的关系。静脉溶栓治疗急性心肌梗塞１１１例，其中５５例使用ＳＫ（１５０万单位／例），５６例使用ＵＫ（１．７－２．３万单位／ｋｇ体重，平均１５３．２５万单位／例），于溶栓前、溶栓后２、６、１２、２４小时、第３天、第７天分别测定血浆纤溶酶原激活物（ＰＡ）、纤溶酶原激活物抑制物（ＰＡＩ）、及纤溶酶原（ＰＬＧ）活性，并测定纤维蛋白原（ＦＧ）浓度、激活的试管法凝血时间（ＡＣＴ）。结果显示：ＳＫ引起的凝血和纤溶系统变化均比ＵＫ明显，特征为：在溶栓后２～６小时有较高的ＰＡ活性和较低的ＰＡＩ活性；溶栓后２小时较长的凝血时间；较低的纤维蛋白原浓度从２小时持续到第７天，上述差异均有极显著意义。本文结果提示ＳＫ对凝血和纤溶系统的影响比ＵＫ强烈而持久，二者在血液学特征上的差异与临床疗效及使用抗凝剂等问题可能有一定的关系。     

Beneficial effects of coronary venous retroinfusion but not left atrial administration of superoxide dismutase on myocardial necrosis in pigs

The efficacy of coronary venous versus left atrial administration of superoxide dismutase was studied in 24 open chest pigs which had 60 min of left anterior descending coronary artery occlusion followed by 3 h reperfusion. The pigs were randomly assigned to three treatment protocols: group A (n = 8) superoxide dismutase (5 mg kg-1) was infused into the great cardiac vein for 30 min beginning 15 min before reperfusion; group B (n = 8) superoxide dismutase (5 mg kg-1) was infused into the left atrium in a similar manner to group A; group C (n = 8) bovine serum albumin (5 mg kg-1) was infused into the great cardiac vein in the same manner as group A. Infarct size, expressed as percent of area at risk, was significantly smaller in group A (28.2 +/- 13.0%) than groups B (58.7 +/- 8.3%) and C (61.6 +/- 7.2%) (P less than 0.05). The results indicate that retroinfusion of superoxide dismutase into the great cardiac vein before reperfusion may be an effective treatment for the prevention of reperfusion injury, even in the absence of a well developed coronary collateral circulation. Antegrade (left atrial) administration of the same amount of superoxide dismutase did not decrease infarct size in pigs. The most likely explanation for this difference in efficacy is that drug delivery with left atrial administration is dependent on antegrade flow with reperfusion which is less reliable and less efficient than coronary venous retroinfusion. The latter provides a predictably high concentration of superoxide dismutase to the jeopardized myocardium during the period of ischaemia before reperfusion.     

Arrhythmias with brief, high-dose intravenous streptokinase infusion in acute myocardial infarction

Cardiac arrhythmias are described during the first 2 h afterbrief, high-dose, intravenous streptokinase infusion in 23 patientswith evolving myocardial infarction was given. A control groupconsisted of 22 similar patients with acute myocardial infarctionnot treated with streptok inase infusion. On the basis of anearly peak of creatine kinase activity successful reperfusionwas achieved in 60.9% of patients. Significantly more ventricularpremature complexes (P<0.01) and paroxysms of idioventricularrhythm (P<0.05) were noticed in the treated group. Prematureventricular complexes did not predict any severe ventriculararrhythmia. Accelerated idioventricular rhythm appears to bethe most specific arrhythmia encountered with thrombolytic therapyof acute myocardial infarction. We propose that in routine clinicalwork it can be used as a bedside sign ofsuccessful reperfusion.     

Acute myocardial infarction with normal coronary arteries. In vivo demonstration of coronary thrombosis during the acute episode

Two cases with acute myocardial infarction are presented. Both had thrombotic occlusion of the infarct-related artery. Following successful thrombolysis with streptokinase, coronary angiography was normal. These cases prove that "myocardial infarction with normal coronaries" can be associated with coronary thrombosis in the acute stage.     

Blood rheology in acute myocardial infarction: effects of high-dose i.v. streptokinase compared to placebo.

To compare the haemorheological effects of an i.v. infusion of 1.5 MU of streptokinase with placebo, we investigated the time course of plasma fibrinogen concentration and the haemorheologic parameters plasma viscosity, erythrocyte aggregation and whole blood viscosity at different shear rates during the early phase of acute myocardial infarction until week 3 in 38 unselected patients from the ISAM and ISIS-2 study. Within 3 h, streptokinase led to a near afibrinogenaemia lasting for more than 24 h. Concomitantly, with streptokinase we found a reduction of plasma viscosity, erythrocyte aggregation and whole blood viscosity, whereas with placebo, values showed a slight increase, resulting in significant differences between the groups within the first 2 days. Thereafter, both groups showed an increase in all parameters, values reaching a maximum after 1 week. The streptokinase-induced reduction in blood viscosity may lead to an improvement in microcirculation in the infarction area during the early phase, whereas the hyperviscosity observed independently of therapy after 1 week may lead to an impairment of microcirculation.     

Intracoronary streptokinase therapy in the coronary care unit for acute myocardial infarction

Intracoronary streptokinase was offered and preliminary coronary angiography performed in 14 patients who were seen with the clinical diagnosis of acute myocardial infarction within 4 h of onset of symptoms. The procedure was performed in the Coronary Care Unit (CCU) of St. Peter's Medical Center with the use of a portable C-arm fluoroscope. Angiography was recorded on video tape. Service was provided by an "on-call" team consisting of two physicians, a CCU nurse, and a radiology technician, on a 24-h service basis. Adequate visualization of coronary anatomy was obtained in all patients. Patency of occluded vessels was achieved in 10 of 11 patients who received intracoronary streptokinase. The initial streptokinase bolus was administered at a mean interval of 4.1 h from onset of symptoms. It is concluded that speedy and effective coronary thrombolytic therapy can be provided in the CCU on a 24-h service basis by an on-call team. The use of CCU for this purpose will make this therapy widely available across the country, without the need for Cardiac Catheterization Laboratory.     

Invasive reperfusion study II. Multicentre European randomized trial of anistreplase vs streptokinase in acute myocardial infarction

IRS II (Invasive reperfusion study II) was a multicentre randomizedtrial comparing the efficacy of a 2–5-min 30 U anistreplaseintravenous injection with a 1 500 000 U 60-min streptokinase(SK) intravenous infusion in acute myocardial infarction. 116patients were randomized within 6 h of onset of symptoms. Earlycoronary patency was assessable in 107 patients by coronaryangiogram performed 102 min after thrombolytic treatment (range:30–297 min) in the anistreplase group and 93 min (range:22–330 min) in the SK group. The early coronary patencyrate was significantly higher in the anistreplase group thanin the SK group: respectively, 70% (38/54) and 51% (27/53),P<0.05. Fifty patients had assessable coronary angiogramsat 90 min and 24 h. The 24-h patency rate was 92.3% (24/26)in the anistreplase group vs 87.5% (21/24) in the SK group.No early reocclusion occurred in the anistreplase group vs 15.4%(2/13) in the SK group (NS). Fibrinogen fell to 13.2 ±19.8%on anistreplase vs 9.4 ±10.3% on SK (NS). Bleeding complicationsoccurred in 12% (7/58) of treated patients in the anistreplasegroup vs 20.7% (13/58) in the SK group (NS). Two cerebrovascularaccidents occurred after thrombolytic treatment with anistreplase(3.4%) vs one after SK (1.7%) (NS). Thus, anistreplase is moreeffective than intravenous SK and easier to administer.     

Effect of Very Early Intravenous Streptokinase Infusion in Patients with Evolving Myocardial Infarction

ABSTRACT The effect of very early infusion of 1.5 × 10⁶ U of streptokinase intravenously was studied in 29 patients with nitroglycerin-resistant chest pain and ST-segment elevation. Infarct size was estimated from maximal LD1 isoenzyme levels, and the diagnosis confirmed by CK-MB determination. Thrombolytic therapy was started within 1 hour of pain onset in 11 patients (group A), between 1 and 2 hours in 10 (group B), and later than 2 hours in eight patients (group C). Marked differences appeared between the groups. Thus, three patients in group A and one patient in group B did not develop infarction, all had critical LAD stenoses. Three patients in group C died in shock without bleeding. Further, the average maximal LD1 values in the 22 patients who survived their infarction differed significantly between the groups, and were 12.6, 19.1 and 36.2 μkat/l in groups A, B and C, respectively. In conclusion, very early intravenous streptokinase infusion probably reduces myocardial necrosis, and possibly prevents infarction in some patients.     

Effectiveness of intravenous streptokinase on infarct size and left ventricular function in acute myocardial infarction. Prospective and randomized study

Within 3 h after the onset of symptoms of myocardial infarction, 64 patients were randomly assigned to receive either a 1-h intravenous infusion of 1,500,000 IU of streptokinase (SK) or a conventional therapy. Infarct size was estimated in CK gram equivalent (CKg) by measurement of CK-MB every 3 hours during a 48-h period. Enzymatic study revealed that myocardial infarction of the SK group was significantly smaller (61.4 +/- 45 vs. 89.4 +/- 56 CKg, p less than .05). Angiograms were performed at early stage and five weeks after myocardial infarction. At first coronary angiogram, the infarct-related vessel was open in 82% in the SK group versus 12% in controls. The SK group had higher global ejection fraction at second angiogram (57 +/- 11% vs. 49 +/- 11%, p less than .02), but differences in regional wall motion were not significant. By analysis according to patency or occlusion of infarct-related vessel, global and regional ejection fractions were significantly better at first and at second angiograms in all patients and in anterior infarctions with a patent infarct-related coronary artery. There was no significant difference for inferior infarction. We conclude that intravenous streptokinase infusion early after the onset of myocardial infarction reduces infarct size and improves left ventricular function, chiefly in anterior infarction. This benefit appears to be closely correlated to patency of infarct-related vessels.     

Percutaneous transluminal coronary angioplasty versus thrombolysis in acute myocardial infarction: A meta-analysis

While percutaneous transluminal coronary angioplasty (PTCA) as a primary modality for treating acute myocardial infarction (MI) has been shown to have important advantages over thrombolysis, a survival benefit has not been demonstrated because of the small size of the individual trials. To increase the statistical power to detect a survival benefit, we performed a meta-analysis of trials of PTCA and thrombolysis. We pooled the data for all randomized, controlled trials; randomized, controlled trials stratified according to thrombolytic agent [streptokinase vs. tissue plasminogen activator (TPA)]; and all trials. Pooling was performed by calculating the Mantel-Haenszel odds ratio with the Robins, Greenland, and Breslow estimate of variance. Calculation of the Q statistic was performed to assess heterogeneity. For all four analyses, the odds ratio indicated a significant survival advantage of PTCA over thrombolysis: all randomized controlled trials [0.57,95% confidence index (CI): 0.48,0.68)]; streptokinase trials [0.61,95% CI: 0.43,0.87); TPA trials (0.52,95% CI: 0.36,0.76); all trials (0.51,95% CI: 0.43,0.61). The Q statistic was not significant for any of the analyses. The results of our meta-analysis support the hypothesis that PTCA is associated with a significant reduction in mortality compared with thrombolysis.     

Reduced occurrence of atrial fibrillation in acute myocardial infarction treated with streptokinase.

In a historical follow-up study of 152 hospital patients with acute myocardial infarction, the frequency of life-threatening arrhythmias (ventricular fibrillation, sustained ventricular tachycardia, 3rd degree AV-block, 2nd degree AV-block (Mobitz type II), and asystole) and atrial fibrillation in 76 patients treated with streptokinase was compared with their frequency in 76 patients who did not receive a thrombolytic therapy. Among those treated with streptokinase two patients (3%) developed atrial fibrillation, compared with 12 (16%) in the control group (P = 0.009). Life-threatening arrhythmias occurred with equal frequency in the two groups. Further studies should confirm and clarify the mechanism of the reduced frequency of atrial fibrillation in the streptokinase-treated patients.     

Prediction of degree of residual stenosis in coronary thrombolysis

In order to predict the residual stenosis in coronary thrombolysis, the factors easily obtained from clinical history--age, gender, history of angina before acute myocardial infarction (AMI), family history, hypertension, diabetes, hypercholesterolemia, smoking, and interval between onset of AMI and recanalization--were observed in 114 patients with successful coronary thrombolysis. In 55 patients with angina before AMI, 29 patients had residual stenosis greater than or equal to 75% and 26 patients had residual stenosis less than 75%. In 59 patients without angina before AMI, 15 patients had residual stenosis greater than or equal to 75%, and 44 patients had residual stenosis less than 75%. The presence or absence of angina before AMI was the main variable that discriminated the groups of residual stenosis of more or less than 75%, which was the only significant independent variable to predict the residual stenosis. These data suggest that the presence of angina pectoris before AMI is likely to be associated with a significant degree of residual stenosis after thrombolysis.     

急性心肌梗死rt—PA溶栓时再灌注性心律失常的观察

目的：了解急性心肌梗死（AMI）静脉溶栓治疗中再灌注性心律失常的类型及其与冠脉再通的关系。方法：分析经重组组织型纤溶酶原激活剂（rt-PA)静脉溶栓治疗的AMI患者37例，根据临床症状，心电图，心肌酶谱的变化和再灌注性心律失常的发生作为判断再通标准。结果：其中24例临床判定再通（再通率64.86%)，20例（83.33%)发生再灌注性心律失常，以加速性室性自主心律最常见。结论：再灌注性心律失常的类型有多种，其中加速性室性自主心律最常见，特异性最高。系预示再灌注的较可靠指标。     

不同溶栓药物和剂量治疗急性心肌梗塞239例对比分析

２３９例急性心肌梗塞（ＡＭＩ）患者接受溶栓治疗，其中采用日本尿激酶（ＵＫ）９６万Ｕ３５例，１５０万Ｕ５５例；国产ＵＫ９６万Ｕ１５例，１５０万Ｕ５３例；德国链激酶（ＳＫ）１５０万Ｕ６６例；国产重组链激酶（ｒＳＫ）１５０万Ｕ１５例。对不同剂量及不同溶栓剂的疗效与安全性进行对比分析发现：１９９２年前国产ＵＫ９６万Ｕ比日本进口ＵＫ９６万Ｕ血管再通率低（２０．０％ｖｓ５１．４％Ｐ＜０．０１）。１９９２年后国产ＵＫ剂量增至１５０万Ｕ，血管再通率显著提高（５６．６％ｖｓ２０．０％Ｐ＜０．０１），与进口ＵＫ１５０万Ｕ的疗效与安全性相近（Ｐ＞０．０５）；国产ｒＳＫ１５０万Ｕ与进口ＳＫ１５０万Ｕ的血管再通率相似（７３．３％ｖｓ６５．２％Ｐ＞０．０５）；且比国产ＵＫ１５０万Ｕ的血管再通率明显提高（７３．３％ｖｓ５６．６％Ｐ＜０．０５），虽然ｒＳＫ轻度出血高于ＵＫ（２６．７％ｖｓ９．４％Ｐ＜０．０１），偶有低血压发生，但不影响疗效。国产ｒＳＫ与ＵＫ比进口ＳＫ和ＵＫ价格低２～４倍。因此认为，国产ｒＳＫ和ＵＫ是较为有效、安全、价廉且适合我国国情的溶栓药物。     

急性心肌梗死静脉溶栓疗效与血脂相关性

目的 :观察血脂水平对急性心肌梗死 （AMI）患者静脉溶栓治疗效果的影响。方法 :对 3 8例 AMI患者的总胆固醇 （TC）、甘油三酯 （TG）、低密度脂蛋白 -胆固醇 （L DL -C）及高密度脂蛋白 -胆固醇 （HDL -C）于发病后 2 4h内进行测定 ,以中华心血管病杂志编委会 ,AMI溶栓疗法参考方案为标准 ,分为再通组 （3 0例 ） ,未通组 （8例 ）。结果 :溶栓再通组与未通组 TC、L DL -C、HDL -C比较差异无显著意义 ,未通组 TG明显高于再通组 （P<0 .0 5）。结论 :TG水平升高可能影响 AMI患者静脉溶栓效果 ,其机制及临床意义有待于进一步研究