Prehospital thrombolysis in acute myocardial infarction

The benefit and risk of prehospital thrombolysis for acute myocardial infarction (AMI) were evaluated in a double-blind randomized trial. Patients presenting less than 4 hours after symptom onset received 2 million units of urokinase as an intravenous bolus either before (group A, n = 40) or after (group B, n = 38) hospital admission. The mean time interval from onset of symptoms to thrombolytic therapy was 85 +/- 51 minutes in group A and 137 +/- 50 minutes in group B (p less than 0.0005). In 91% of the patients, thrombolytic therapy was administered less than 3 hours after symptom onset. Complication rates during the pre- and in-hospital period were low and did not differ between groups. Three patients died (1 in group A, 2 in group B) from reinfarction 7 to 14 days after admission. Left-sided cardiac catheterization before discharge revealed a patency rate in the infarct-related artery of 61% in group A and 67% in group B (difference not significant). Global left ventricular function and regional wall motion at the infarct site did not differ significantly between group A and B (ejection fraction 51 +/- 10%, n = 28 vs 53 +/- 14%, n = 28; wall motion -2.3 +/- 1.3 vs -2.2 +/- 1.1 standard deviation, respectively). Also, peak creatine kinase did not differ significantly (838 +/- 634 U/liter in group A vs 924 +/- 595 U/liter in group B). Prehospital thrombolysis using a bolus injection of urokinase has a low risk when performed by a trained physician with a mobile care unit. The saving of 45 minutes in the early stage of an acute infarction through prehospital thrombolysis did not appear to be important for salvage of myocardial function.     

Prehospital thrombolysis with alteplase (rt-PA) in acute myocardial infarction.

The improvement in survival in patients undergoing thrombolytic therapy in myocardial infarction is determined by the delay between coronary occlusion and reperfusion. The REPerfusion in Acute Infarction Rotterdam (REPAIR) study was designed to examine the feasibility and safety of prehospital thrombolysis with alteplase (rt-PA, 'Actilyse'). A small portable ECG computer system is used to confirm the presence of a large myocardial infarction (at least 1.0 mV ST-deviation) 'on the spot'. Between 22 June 1988 and 1 January 1991, 226 patients were treated by the ambulance service after the evaluation of 9052 patients complaining of chest pain. Therapy could be initiated within an average of 100 +/- 56 min (SD) after the onset of symptoms, and within 22 +/- 9 min after ambulance arrival. Three patients were defibrillated during transportation. Six patients (3%) died after arrival in the hospital. The time gained by prehospital treatment was 47 min (95% confidence limits 44-51 min) in comparison with 220 patients who did not meet the criteria for prehospital thrombolysis, but received thrombolytic therapy as soon as possible after hospital admission. The developed procedure allows rapid and safe initiation of thrombolytic therapy in selected patients, even in the absence of a physician. The observed low mortality supports the concept that prehospital thrombolytic therapy is indeed beneficial to the patient.     

Macroscopic hemorrhagic infarction following selective coronary thrombolysis in acute myocardial infarction

Macroscopic hemorrhagic infarction was studied in 14 autopsied hearts with selective coronary thrombolysis (SCT) after acute myocardial infarction (AMI). In all patients urokinase, 240,000 - 720,000 units, had been selectively injected into ischemia-related coronary artery at 2 - 7 hours after the onset of AMI. The degree of stenosis after SCT was 90 - 99% in 13 patients and 100% in one patient. According to the duration of illness at death, the 14 patients were classified into 3 stages; stage I: 4 - 9 hours; stage II: 15 hours to 11 days; stage III: 19 days to 12 months. Three hearts in stage I had no macroscopic hemorrhage. In stage II, marked and diffuse hemorrhage in the infarct area was macroscopically evident in 6 of 7 hearts. In a stage II patient, extravasation of contrast medium into the myocardium was found at 3 hours after the onset of AMI. In stage III, 4 hearts had massive fibrosis or granulation in the left ventricular wall without macroscopic hemorrhage. Cardiac rupture was seen in 4 of 10 patients from stages I and II. It is concluded that macroscopic bleeding appears in most patients with AMI treated with coronary thrombolysis. In the majority of cases, the hemorrhage increases gradually after SCT and becomes macroscopically definite approximately 15 hours after the onset of AMI. Rarely, massive bleeding appears earlier. Hemorrhagic infarction is replaced by massive fibrosis after approximately 2 weeks.     

The conservative coronary angioplasty strategy after thrombolysis for acute myocardial infarction: immediate and short-term results.

The in-hospital and short-term follow-up results of a conservative coronary angioplasty approach in 354 consecutive patients treated after thrombolysis for acute myocardial infarction were compared with results obtained in 408 control noninfarcted patients treated for the classical indication of myocardial ischemia. Only 20% of the study patients underwent angioplasty during the initial hospitalization period and the clinical success rate was 93% versus 95% in the control group (p = NS). No significant differences in the total number of in-hospital untoward events were observed (10.2% and 7.6%, respectively). During a 7.4 +/- 1.5 month follow-up period, the total number of adverse events was only 16.9% in the study patients but it was 27.8% in the control group (p < 0.001). There were no significant differences in death, myocardial infarction, or coronary surgery as individual events, but repeat angioplasty was less frequent in the study group (14.0% versus 21.5%, p < 0.01). Thus in-hospital results in patients undergoing angioplasty on a deferred basis after thrombolysis for myocardial infarction were largely comparable with those results obtained in noninfarcted patients. Moreover, short-term clinical follow-up events were reduced when compared with the control group, an observation apparently largely related to the subgroup without clinical evidence of residual ischemia.     

Angiographic findings in the coronary arteries after thrombolysis in acute myocardial infarction.

The angiographic appearance of the coronary arteries was examined in 308 patients with acute myocardial infarction (AMI) who received high-dose intravenous thrombolytic therapy. Coronary angiography was performed on day 7 after admission to the hospital. Patients had an average of 2.4 discrete arterial narrowings or obstructions. The narrowings were proximal and related to bifurcations. Four fifths of the culprit arteries were patient; 104 (34%) had a ruptured plaque, 22 (7%) had an ulcerated plaque, and in 190 (62%) the lesions were eccentric. Patients differed from a comparable, previously studied, control series of 302 patients with chronic stable angina pectoris who had more extensive disease. They had 5.7 narrowings/patient, also located proximally and at bifurcations, but more widely distributed in the coronary tree. Patients with AMI who are suitable for thrombolysis have a unique coronary angiographic picture. The data confirm that AMI is caused by sudden rupture of a localized atheromatous plaque that initiates an obstructive thrombotic cascade.     

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.     

急性心肌梗死时尿激酶溶栓加即刻准备的冠状动脉内支架置入术

目的：探讨急性心肌梗死（AMI）时尿激酶溶栓加即刻血管造影，TIMIⅡ级或以下时进行冠状动脉内支架置入术（支架术）的安全性。方法：选择1999年1月至2001年12月AMI（发病6h以内）患25例，常规应用尿激酶（商品名：天普洛欣）150万U0.5h内静脉滴注，其中6例无创指标未见再通，25例患90min后即刻血管造影，其中13例TIMIⅡ级或以下进行冠状动脉内支架置入术。结果：13例TIMIⅡ级或以下均成功进行冠状动脉内支架置入术，术后冠脉血流均达到TIMIⅡ级，未见需要输血的严重出血并发症。结论：AMI时尿激酶溶栓加即刻准备的支架术安全、疗效好。     

Repeat thrombolysis in acute myocardial infarction

The author describes a case-history of streptokinase intolerance during treatment of acute myocardial infarction (IM) where it was impossible to ensure rescue percutaneous coronary angioplasty (PTCA) and to resolve this condition by subsequent alteplase treatment. The author discusses whether it is justified and indicated to use this procedure rarely mentioned in the literature.     

Emergency thrombolysis in acute myocardial infarction

The goal of thrombolytic treatment in acute myocardial infarction is to reestablish permanent blood flow, salvage ischemic myocardium, and reduce mortality. If patency is achieved sufficiently early and is maintained, left ventricular function is preserved and mortality decreases. The recent experience with tissue plasminogen activator and streptokinase in the TIMI I trial is reviewed with specific attention to reperfusion, reocclusion, and bleeding. Other studies concerning left ventricular preservation and mortality are also discussed. Current guidelines for antithrombotic therapy and thrombolysis are discussed. It is extremely important to adequately select patients to avoid side effects. Thorough lysis of the thrombus must be achieved to reduce the risk of rethrombosis. Simultaneous heparin should be administered to treat ongoing thrombosis. Additional antithrombotic therapy with aspirin and acute vasodilation to reduce vasoconstriction probably also decrease the likelihood of reocclusion. Because this treatment predisposes to bleeding, extreme care should be taken to avoid vascular punctures and invasive procedures in these patients. The association of immediate percutaneous transluminal coronary angioplasty has not been beneficial in preventing further events; on the contrary, adverse effects have been associated with this acute intervention.     

Improved prognosis after coronary thrombolysis with urokinase in acute myocardial infarction

The effectiveness of coronary thrombolysis with urokinase (UK) on short- and long-term outcome after acute myocardial infarction was studied by comparison of 120 patients treated with UK and 124 with conventional therapy followed up for a period of 20 months. UK was administered to patients within 6 hours of the onset of chest pain, by the intracoronary route (20,000 U/min, at a mean dose of 698,000 U) in 46 patients, intravenously (960,000 to 1,920,000 U in 15 or 30 min, at a mean dose of 1,293,000 U) in 56 patients and by the combined route (at a mean dose of 2,333,000 U) in 18 patients. Complete occlusion or 99% stenosis with severe delay of the contrast medium was found in 72.5% and recanalization by UK was achieved in 68.0%. Cumulative mortality rate was significantly reduced in the UK group (9.2% vs. 29.0%). Cardiac death from recurrent MI was also significantly reduced (2.5% vs. 10.5%). The reduction in mortality rate was demonstrated even in older patients as well as in those cases graded as severe according to the Killip and Forrester classifications. Thus, it is concluded that coronary thrombolysis with UK therapy improves the prognosis of acute myocardial infarction.     

Intracoronary thrombolysis in acute myocardial infarction

Forty-seven patients with acute myocardial infarction (MI) underwent intracoronary infusion of Thrombolysin or streptokinase. In 41, a completely reoccluded artery was reopened. Patency was associated with appearance of arrhythmias, relief of pain, gradual return of the ST-segment to the baseline and appearance of abnormal Q waves. Creatine kinase (CK) and MB-CK enzyme levels peaked earlier. Serial thallium scintigrams showed reduction in defect size after reperfusion, and the ejection fraction was higher compared with control. Eighteen patients were recommended for coronary bypass surgery for recurrent pain or severe multivessel disease.     

Six-year survival after coronary thrombolysis and early revascularization for acute myocardial infarction.

Six-year follow-up was conducted in a consecutive series of 192 patients receiving thrombolytic therapy for acute myocardial infarction (AMI) with ST-segment elevation. Cardiac catheterization was performed within a day, and patients with an open infarct artery routinely had early revascularization: 99 (67%) underwent coronary bypass surgery and 18 (12%) coronary angioplasty. With this treatment strategy, 6-year cardiac mortality was 14.5%, 6% (12 patients) in hospital and 9% (16 patients) for survivors of hospitalization. Multivariate analysis showed that predictors of cardiac death among survivors of hospitalization were a closed infarct artery at catheterization (p less than 0.01), diabetes (p less than 0.01) and anterior myocardial infarction (p = 0.01). A subset of 146 patients underwent radionuclide angiography before hospital discharge; for them, predictors of mortality were a closed infarct artery at catheterization (p less than 0.01), anterior wall AMI (p = 0.02), and Killip class III to IV on admission (p less than 0.06). Left ventricular ejection fraction was not a significant predictor of mortality for this subset of patients.     

Efficacy of coronary angioplasty following conventional coronary thrombolysis in patients with acute myocardial infarction

The efficacy of combined thrombolysis and angioplasty for the purpose of coronary reperfusion after acute myocardial infarction has been controversial. The present study was conducted, therefore, to evaluate the effects of angioplasty following administration of conventional thrombolytic agents on the long-term prognosis of acute myocardial infarction patients. A total of 409 patients admitted to the hospital within 12 hours of the onset of infarction between January 1990 and May 2001 were studied retrospectively. These included 151 patients treated with thrombolysis alone (group T), 73 patients treated with angioplasty alone (group A), and 35 patients treated with angioplasty after thrombolysis (group T&A). Group T&A had shorter intervals from onset to initial treatment than group A (3.0 hours vs 6.3 hours, p < 0.01), a higher reperfusion success rate than group T (91.4% vs 74.8%, p < 0.01), and more improved left ventricular wall motion than group A. One-year cardiac mortality rates tended to be higher in group T, which had a higher rate of unsuccessful reperfusion than groups T&A or A (8.1% vs 3.4% vs 3.5%). The frequencies of hemorrhagic complications were similar among the 3 groups. From these findings, we conclude that thrombolytic therapy with subsequent angioplasty is an effective strategy for achieving cardiac reperfusion following acute myocardial infarction.     

Acute electrocardiographic changes associated with successful coronary thrombolysis in acute myocardial infarction

In this study ECG changes were analyzed to assess the acute effects of antegrade blood flow on the ECG in patients with AMI. The study population consisted of 22 patients with MI in whom the totally occluded left anterior descending artery (LAD) or right coronary artery (RCA) was recanalized by intracoronary urokinase infusion (recanalized group) and 14 patients in whom the occluded coronary artery was not successfully recanalized (control group). No significant difference was found in the sum of ST segment elevation (V2-V4 leads for the LAD-occluded group, II, III and aVF leads for the RCA-occluded group) before urokinase infusion. In the recanalized group sigma ST abruptly increased in 5 min after recanalization in 13 of 16 LAD-occluded patients from 1.49 +/- 0.89 mV to 2.44 +/- 1.67 mV (p less than 0.005), and in 4 of 6 RCA-occluded patients from 0.66 +/- 0.12 mV to 1.42 +/- 0.52 mV (p less than 0.01). However increased sigma ST in the recanalized group was reduced to the control value existing before recanalization within 30 min after recanalization and continued to decline more rapidly than in the control group. These transient ST segment elevations were not correlated with long-term angiographic determinants of left ventricular function. We conclude that ST segment shows abrupt augmentation after successful thrombolysis and that continuous ST segment monitoring is useful for assessing thrombolysis in AMI.