High dose intravenous streptokinase in acute myocardial infarction--short and long term prognosis

Streptokinase (1 million international units) was given intravenously over 30 or 60 minutes to 50 patients four hours or less after the onset of acute myocardial infarction. All were aged less than or equal to 70 years and had 4 mm or greater ST segment elevation in anterior or inferior leads. Rapid (mean 95 min) ST segment resolution, which was taken to indicate reperfusion of the myocardium, occurred in 36 (72%) patients. In these 36 the average time from onset of symptoms to peak creatine kinase, creatine kinase MB, and myoglobin was 9.45 hours, whereas it was 17 hours in the 14 patients in whom indirect criteria did not indicate reperfusion. Reperfusion arrhythmias were invariably present and ventricular tachycardia developed in five patients and ventricular fibrillation in two. The infarct related artery was seen to be open in 28 (70%) of the 40 patients who had delayed coronary arteriography. The frequency of patency in the infarct related artery was no different in patients given streptokinase less than 2 hours or between 2-4 hours from onset of symptoms nor did it differ when streptokinase was infused over 30 or 60 minutes. Mean left ventricular ejection fraction was 57% in those with a patient infarct related artery and 48% in those with an occluded vessel. Eight patients subsequently underwent elective percutaneous transluminal coronary angioplasty after successful thrombolysis and six had coronary artery bypass grafting. There were nine in-hospital reocclusions of the infarct related coronary arteries. Two bleeding episodes occurred; one required transfusion. Five of the 50 patients died in hospital. All of them had had an anterior myocardial infarction; four had bifascicular block and one had right bundle branch block. During follow up, four patients died, two suddenly and two from reinfarction. During follow up (mean 15 months) the frequency of reinfarction, dyspnoea, and angina was low and there was no difference in the proportions of patients returning to work between those with an open infarct related artery and those with a closed infarct related artery. Intravenous administration of high dose streptokinase to selected patients during the acute phase of myocardial infarction is a safe, effective, and practical method of thrombolysis. It must, however, be followed by coronary arteriography to select those patients in whom percutaneous transluminal coronary angioplasty or coronary artery bypass grafting will be helpful.     

Early thrombolysis in acute myocardial infarction: limitation of infarct size and improved survival

The effect of thrombolysis in acute myocardial infarction on infarct size, left ventricular function, clinical course and patient survival was studied in a randomized trial comparing thrombolysis (269 patients) with conventional treatment (264 control patients). All 533 patients were admitted to the coronary care unit within 4 hours after the onset of symptoms related to the infarction. Baseline characteristics were similar in both groups. Informed consent was requested only of patients allocated to thrombolysis; no angiography was performed in 35. The infarct-related artery was patent in 65 patients and occluded in 169. Recanalization was achieved in 133 patients. The median time to angiographic documentation of vessel patency was 200 minutes after the onset of symptoms. The clinical course in the coronary care unit was more favorable after thrombolysis. Infarct size, estimated from myocardial enzyme release, was 30% lower after thrombolysis. In patients admitted within 1 hour after the onset of symptoms the reduction of infarct size was 51%, in those admitted between 1 and 2 hours it was 31% and in those admitted later than 2 hours it was 13%. Left ventricular function measured by radionuclide angiography before hospital discharge was better after thrombolysis (ejection fraction 48 +/- 15%) than in control patients (44 +/- 15%). Similar improvement was observed in patients with a first infarct only (thrombolysis 50 +/- 14%, control subjects 46 +/- 15%), in patients with anterior infarction (thrombolysis 44 +/- 16%, control subjects 35 +/- 14%) and in those with inferior infarction (thrombolysis 52 +/- 12%, control subjects 49 +/- 12%). Similar results were obtained by contrast angiography. Mortality was lower after thrombolysis. After 28 days 16 patients allocated to thrombolysis and 31 control patients had died. One year survival rates were 91 and 84%, respectively. On the other hand, nonfatal reinfarction occurred more frequently after thrombolysis (36 patients) than in control subjects (16 patients). Early thrombolysis by intracoronary streptokinase leads to a smaller infarct size estimated by enzyme release, preserves left ventricular function at the second week and leads to improved 1 year survival.     

Thrombolytic therapy in acute myocardial infarction

The effect of thrombolysis in acute myocardial infarction on infarct size, left ventricular function, clinical course and patient survival was studied in a randomized trial comparing thrombolysis (269 patients) with conventional treatment (264 control patients). All 533 patients were admitted to the coronary care unit within 4 hours after the onset of symptoms related to the infarction. Baseline characteristics were similar in both groups. Informed consent was requested only of patients allocated to thrombolysis; no angiography was performed in 35. The infarct-related artery was patent in 65 patients and occluded in 169. Recanalization was achieved in 133 patients. The median time to angiographic documentation of vessel patency was 200 minutes after the onset of symptoms. The clinical course in the coronary care unit was more favorable after thrombolysis. Infarct size, estimated from myocardial enzyme release, was 30% lower after thrombolysis. In patients admitted within 1 hour after the onset of symptoms the reduction of infarct size was 51%, in those admitted between 1 and 2 hours it was 31% and in those admitted later than 2 hours it was 13%. Left ventricular function measured by radionuclide angiography before hospital discharge was better after thrombolysis (ejection fraction 48 ± 15%) than in control patients (44 ± 15%). Similar improvement was observed in patients with a first infarct only (thrombolysis 50 ± 14%, control subjects 46 ± 15%), in patients with anterior infarction (thrombolysis 44 ± 16%, control subjects 35 ± 14%) and in those with inferior infarction (thrombolysis 52 ± 12%, control subjects 49 ± 12%). Similar results were obtained by contrast angiography. Mortality was lower after thrombolysis. After 28 days 16 patients allocated to thrombolysis and 31 control patients had died. One year survival rates were 91 and 84%, respectively. On the other hand, nonfatal reinfarction occurred more frequently after thrombolysis (36 patients) than in control subjects (16 patients). Early thrombolysis by intracoronary streptokinase leads to a smaller infarct size estimated by enzyme release, preserves left ventricular function at the second week and leads to improved 1 year survival.

Originally published in the Journal of the American College of Cardiology, April 1986.     

Advances in intracoronary thrombolysis treatment

Based on the results of intracoronary thrombolysis in 30 patients with initial onset of anterior myocardial infarction, we concluded that: (1) left ventricular function and clinical features are markedly improved when reperfusion is accomplished within four hours after coronary artery occlusion; and (2) intracoronary thrombolysis therapy should be considered possible up to 10 hours after the onset of myocardial infarction to prevent expansion of infarct sizes and to preserve ventricular functions. Not infrequently, there is a significant stenosis at the site of initial occlusion after thrombolytic therapy, which results in an immediate reocclusion. Consequently, percutaneous transluminal coronary angioplasty (PTCA) is now widely performed after thrombolytic treatment to achieve more definite revascularization. Our early experiences showed that PTCA following thrombolytic treatment has an increased potential for reinfarction rather than added benefits for left ventricular functions. More recently, however, since our PTCA technique has been improved so as to achieve sufficient dilatation of the stenosed coronary artery, there has been less tendency to immediate reinfarction after the procedure for acute myocardial infarction. Whether PTCA should be added to thrombolytic therapy during the acute phase of myocardial infarction is controversial. The alternative is to wait until it can be performed on an elective basis. It is obvious that early revascularization is essential for preserving left ventricular functions after acute myocardial infarction. For this reason, thrombolytic agents such as tissue plasminogen activator and plasminogen proactivator, which can be administered intravenously, are being intensively sought using molecular biological techniques. The ideal thrombolytic agents should have more fibrin-specific properties with longer half-lives than currently-available substances. However, so far none of these novel agents, have been studied in patients.     

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.     

Assessment of residual coronary arterial stenosis after thrombolytic therapy during acute myocardial infarction

Maximal myocardial salvage appears to be related to the severity of residual coronary arterial stenosis after thrombolysis. The degree of residual infarct vessel stenosis was assessed in 119 consecutive patients with patent arteries who received streptokinase during acute myocardial infarction. After administration of streptokinase, 99 of 119 patients (83%) had a residual stenosis 70% or more in diameter. Assuming that a residual diameter stenosis of at least 70% is flow limiting, the feasibility for percutaneous transluminal coronary angioplasty (PTCA) was determined by the following criteria: length less than 10 mm, no significant distal narrowing or left main stenosis, and an adequate-sized distal artery. In 81 of 99 patients (82%), arterial anatomy was suitable for PTCA. Thus, after therapy with streptokinase for acute myocardial infarction, most patients have a significant infarct arterial residual stenosis and are candidates for PTCA.     

Relation between electrocardiography and coronary angiography findings in the infarct stage

One hundred and fifty-two patients underwent cardiac catheterization and coronary arteriography within 6.3 +/- 6.0 hours from onset of acute myocardial infarction. All had a standard 12-lead electrocardiogram recorded within 1.5 hours of cardiac catheterization. The electrocardiographic abnormalities present were correlated with the infarct related artery as determined by coronary arteriography. ST segment elevation was the most common finding in patients with the left anterior descending (LAD), or right coronary artery (RCA) as the infarct related artery. ST segment depression was the most common abnormality in patients with left circumflex artery (CX) as the infarct related artery. A typical pattern of anterior acute myocardial infarction was seen in 93% of all patients with the LAD as the infarct related artery. A typical pattern of acute inferior myocardial infarction was seen in 53% of all patients with RCA or CX narrowing taken as one group. The pattern of true posterior or posterolateral wall acute myocardial infarction in the absence of typical changes in the inferior leads was highly specific and predictive of CX narrowing. In contrast, the pattern of an inferior wall myocardial infarction, in the absence of true posterior or lateral wall changes, was highly specific and predictive of right coronary artery narrowing. Fifty-six percent of patients with CX artery as the infarct related artery presented with non-classical electrocardiographic abnormalities. The electrocardiographic pattern in patients with subtotal occlusions were similar to those of patients with total occlusions. Thus the electrocardiogram obtained in the first few hours of acute myocardial infarction is reliable in localizing the LAD as the infarct related artery.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reinfarction after thrombolytic therapy for acute myocardial infarction followed by conservative management: incidence and effect of smoking

A group of 456 consecutive patients seen less than or equal to 6 h after the onset of acute myocardial infarction associated with ST segment elevation received thrombolytic therapy and were followed up for 12 months. Intravenous streptokinase was given to 315 patients and recombinant tissue-type plasminogen activator (rt-PA) to 141 patients. Reinfarction rate and risk factors for reinfarction were assessed. Management after thrombolysis was conservative; revascularization procedures were reserved for patients with symptoms refractory to medical therapy or for those with left main coronary artery stenosis. Coronary artery surgery or angioplasty was performed in only 3.7% of patients during the first 30 days after thrombolysis and in only 8.6% by 1 year. Most patients (79%) underwent coronary arteriography. Twenty-six patients (5.7%) exhibited signs of threatened reinfarction at 1 month after thrombolytic therapy as did 43 patients (9.4%) by 1 year. Reinfarction was prevented in four of these patients by early readministration of thrombolytic therapy. Multivariate analysis of possible risk factors for reinfarction identified at the time of initial infarction showed current cigarette smoking to be the only predictive factor (reinfarction occurred in 12.5% of smokers versus 6.3% of nonsmokers, p = 0.04). A second analysis of risk factors identified 3 weeks after initial infarction, including the severity of residual stenosis at coronary arteriography and exercise test variables, again showed continued cigarette smoking to be the only factor predictive of reinfarction. Twenty percent of patients who continued to smoke developed reinfarction compared with 5.1% of those who stopped (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Early treatment of acute myocardial infarction with intravenous streptokinase. A high-risk syndrome

Fifty-one successive patients treated with intravenous streptokinase 1.7 +/- 0.8 (mean +/- SD) hours after onset of symptoms of acute myocardial infarction were evaluated during a three-month posthospital follow-up period. Coronary angiography was performed four to nine days after the initial hospital admission. Twenty-eight patients had a second late angiogram. Forty-one patients had successful reperfusion but only 25% of all patients were without significant clinical cardiovascular manifestations during this period. Postmyocardial infarction angina pectoris occurred in 21 patients, an abnormal stress test result was present in 28 patients, eight patients developed congestive heart failure, and five patients had reinfarction. An intervention with percutaneous transluminal coronary angioplasty or coronary artery bypass graft was performed in 15 (37%) of 41 reperfused patients. A significantly higher intervention rate was present in patients treated with streptokinase within one hour following the onset of symptoms. Early reocclusion (within three months of the infarct) was noted in patients with 60% or more residual stenosis in their infarct-related coronary artery. These patients also had a significantly greater incidence of angina pectoris. Our findings indicate that early thrombolytic therapy of acute myocardial infarction preserves myocardium, and since the infarct-related artery is patent, but narrowed, the jeopardized area is responsible for a high-risk syndrome with an increased likelihood of ischemic symptoms. An early aggressive approach may be indicated, especially for patients with greater than 60% residual stenosis in their infarct-related coronary artery.     

Early intervention in acute myocardial infarction: significance for myocardial salvage of immediate intravenous streptokinase therapy followed by coronary angioplasty

Sixteen patients with acute myocardial infarction underwent treatment with streptokinase up to 3 hours after the onset of chest pain. Nine patients (group I) received streptokinase within 1 hour of the onset of pain, and seven patients (group II) received it within 2 to 3 hours. All underwent multigated radionuclide ventriculography after streptokinase therapy and 1 week later. Percutaneous transluminal coronary angioplasty of the infarct artery was performed within 24 hours in all patients. An effort-limited treadmill stress test was performed before discharge. There was no mortality or serious complication. Mean peak total creatine kinase was 521 +/- 289 mU/ml in group I, and 1,614 +/- 709 mU/ml in group II (p less than 0.05). The mean initial left ventricular ejection fraction was 47 +/- 11% in group I and 37 +/- 10% in group II. After early angioplasty (within 24 hours) and at 1 week recovery, left ventricular ejection fraction increased to 53 +/- 9% in group I (p less than 0.05) and to 40 +/- 7% in group II (p = NS). Seven of the nine patients in group I had normal radionuclide ventriculograms at discharge compared with none of the seven patients in group II. Thrombolytic therapy administered less than 1 hour after the onset of symptoms of acute myocardial infarction followed by angioplasty of the infarct artery results in preservation of left ventricular function, whereas therapy given after 2 hours has only a limited effect.     

Intracoronary thrombolysis in evolving myocardial infarction. Sequential angiographic analysis of left ventricular performance

Since November 1979 left ventricular angiography and coronary arteriography have been performed in 80 patients with evolving acute myocardial infarction in order to attempt coronary recanalisation by local streptokinase infusion. The average delay between the onset of symptoms and streptokinase infusion was 3.6 hours. Thrombolysis was successful in 64% of cases. No serious complications related to the procedure were noted. Of the 12 patients in cardiogenic shock, recanalisation was achieved in only four, of whom two survived. To evaluate the left ventricular salvage resulting from early recanalisation the last 58 patients had a second left ventricular angiogram and further coronary arteriograms 21 +/- 10 days later and 16 patients had a third study three months later. From the left ventricular angiogram in the right anterior oblique projection the ejection fraction and two graphic variables of regional wall motion were computed quantifying the hypokinetic zone. Patients were divided into two groups, according to the patency of the infarct related artery at the second control: group 1 consisted of 28 patients with successful recanalisation confirmed, and group 2 of 30 patients in whom no recanalisation was achieved or secondary reocclusion had occurred. At the second study the ejection fraction was unchanged in group 1 but had significantly decreased in group 2. Regional wall motion improved in group 1 and worsened in group 2, more so in patients without recanalisation than in those in whom secondary reocclusion had occurred. The third study showed a further decrease in ejection fraction in group 2. A progressive decrease in percentage residual stenosis was observed in group 1. This sequential angiographic study confirms the partial myocardial salvage resulting from early coronary recanalisation during acute myocardial infarction.     

Intravenous streptokinase during acute myocardial infarction. A prospective open study

To evaluate the efficacy of intravenous streptokinase in acute myocardial infarction (AMI) 108 patients received a high-dose (1.5 million units), short-term infusion (60 minutes) within 6 hours after onset of symptoms, followed by anticoagulation. Before discharge a submaximal exercise test and a coronary arteriography were performed in 100 surviving patients. Sixty-seven patients had a patent infarct-related vessel. Clinical reocclusion occurred in 21 patients. Left ventricular function was slightly, but not significantly, better in patients with patent infarct-related vessels: ejection fraction 59.5 +/- 13% versus 57.4 +/- 13%. Additional procedures were performed in 20 patients: percutaneous transluminal coronary angioplasty (PTCA) in 8 and coronary artery bypass surgery (CABG) in 12. The results indicate that streptokinase applicated during a 6 hour-time window is a potent thrombolytic agent in acute myocardial infarction with limited effect on global left ventricular function. Pre-discharge evaluation is necessary to screen patients for residual ischemia.     

Intracoronary thrombolysis in evolving myocardial infarction. Sequential angiographic analysis of left ventricular performance.

Since November 1979 left ventricular angiography and coronary arteriography have been performed in 80 patients with evolving acute myocardial infarction in order to attempt coronary recanalisation by local streptokinase infusion. The average delay between the onset of symptoms and streptokinase infusion was 3.6 hours. Thrombolysis was successful in 64% of cases. No serious complications related to the procedure were noted. Of the 12 patients in cardiogenic shock, recanalisation was achieved in only four, of whom two survived. To evaluate the left ventricular salvage resulting from early recanalisation the last 58 patients had a second left ventricular angiogram and further coronary arteriograms 21 +/- 10 days later and 16 patients had a third study three months later. From the left ventricular angiogram in the right anterior oblique projection the ejection fraction and two graphic variables of regional wall motion were computed quantifying the hypokinetic zone. Patients were divided into two groups, according to the patency of the infarct related artery at the second control: group 1 consisted of 28 patients with successful recanalisation confirmed, and group 2 of 30 patients in whom no recanalisation was achieved or secondary reocclusion had occurred. At the second study the ejection fraction was unchanged in group 1 but had significantly decreased in group 2. Regional wall motion improved in group 1 and worsened in group 2, more so in patients without recanalisation than in those in whom secondary reocclusion had occurred. The third study showed a further decrease in ejection fraction in group 2. A progressive decrease in percentage residual stenosis was observed in group 1. This sequential angiographic study confirms the partial myocardial salvage resulting from early coronary recanalisation during acute myocardial infarction.     

Three-year follow-up of patients with silent ischemia in the subacute phase of myocardial infarction after thrombolysis and early coronary intervention

In order to assess the prognostic value of silent myocardial ischemia in acute myocardial infarction after thrombolysis and early coronary angiography (14-48 h after start of thrombolysis) including percutaneous transluminal coronary angioplasty, if indicated, 126 patients underwent 24 h-Holter-monitoring in the early postinfarction period. The 24 h-Holter-recording was initiated directly after early coronary intervention (40+/-11 h after onset of symptoms). Of the 126 patients initially eligible for the study 29 had to be excluded from further analysis for clinical or methodical reasons. Of the remaining 97 patients, 10 (10%) had silent ischemia (group A) and 87/97 (90%) patients showed no significant ST-segment alterations. Both groups did not significantly differ from each other with regard to baseline clinical characteristics, severity of coronary artery disease and frequency of successful percutaneous transluminal coronary angioplasty. The left ventricular ejection fraction showed a trend towards lower values in patients with than in those without silent ischemia (47+/-15% vs. 55+/-13%, p=0.07). When both silent ischemia and left ventricular ejection fraction <40% were present, a subset of patients at high risk for cardiac death could be identified (specificity: 98%, positive predictive accuracy: 75%). By Kaplan-Meier analysis, significantly more cardiac deaths occurred in group A than in group B (30% vs. 6%, p<0.01) during the three-year follow-up (950+/-392 days) after acute myocardial infarction. Regarding the cardiac events during long-term follow-up (emergency percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, non-fatal reinfarction, and cardiac death) there was no significant difference between both groups (30% vs. 18%, NS). In conclusion, Holter monitor-detected silent ischemia in the subacute phase of myocardial infarction after thrombolysis followed by early delayed coronary intervention occurs in 10% of the patients indicating either a residual ischemia in the infarcted zone despite a combined reperfusion strategy or a remote ischemic potential in case of multivessel disease. In this small selected group of infarct patients too, silent ischemia is to be considered as an important non-invasive parameter to predict cardiac death during long-term follow-up and provides valuable complementary information to left ventricular dysfunction, a well established prognostic marker in the postinfarction period.     

Coronary artery thrombolysis in acute myocardial infarction

Coronary thrombolysis with streptokinase infusion can be achieved if performed during the first 4 hours of the onset of myocardial infarction. It has been a consistent finding that lysis of the thrombus can reestablish angiographically documented, antegrade coronary flow. Restoration of blood flow and preservation of ischemic myocardium can be achieved after coronary thrombolysis. Coronary artery bypass surgery or percutaneous transluminal coronary angioplasty may be necessary when significant obstructive coronary artery lesions due to atherosclerotic plaques remain after successful thrombolysis.     

Intravenous streptokinase in acute myocardial infarction at the community hospital: a six-year experience

The efficacy of intravenous streptokinase in the initial management of acute myocardial infarction was evaluated over a 6-year period in 130 patients admitted to 3 community hospitals. Most patients were admitted within 2 hours of onset of symptoms and received 1.5 million units of streptokinase over a 30- to 60-minute period. Clinical observations and serial creatine phosphokinase-MB were indicative of vessel patency in 115 (88%) of the patients after initiation of thrombolysis. Of this group, 105 underwent catheterization, and recanalization was demonstrated in 97 (92%). Fifty percent of the patients who underwent reperfusion were subsequently maintained with medical therapy; 50% underwent either percutaneous transluminal coronary angioplasty or coronary artery bypass surgery. Major morbidity was confined to hematomas; no cerebral bleeding was encountered. There was 1 early death from cerebral thrombosis and 2 late deaths, 1 to cancer and 1 to myocardial infarction. These findings suggest the benefit of intravenous streptokinase thrombolysis in patients with acute myocardial infarction presenting within 3 hours of onset of pain, unless specific potential bleeding problems exist or in the case of certain very elderly persons. In addition, the trial demonstrated the feasibility of triaging patients who have undergone lytic therapy to a central facility for catheterization and management.     

Acute coronary artery obstruction in myocardial infarction: overview of thrombolytic therapy

Pump failure, ranging from ventricular dysfunction to acute cardiogenic shock, is now the leading cause of cardiac death. Efforts at temporary mechanical or pharmacologic support of the heart have been largely unsuccessful so that attention is now directed toward prevention of ventricular failure and limitation of myocardial infarct size or even outright prevention of infarction itself. In particular, attention has been refocused on earlier reperfusion efforts with streptokinase. The effect of thrombolysis in acute myocardial infarction on enzymatic infarct size, left ventricular function and early mortality was studied in subsets of patients in a randomized trial (Netherlands Interuniversity Cardiology Institute). Early thrombolytic therapy with intracoronary streptokinase (152 patients) or with intracoronary streptokinase preceded by intravenous streptokinase (117 patients) was compared with conventional treatment (264 patients). All 533 patients were admitted to the coronary care unit within 4 hours after onset of symptoms indicative of acute myocardial infarction. Of the patients eligible for this detailed analysis, 245 were allocated to thrombolytic therapy and 243 to conventional treatment. Early angiography was preformed in 212 of the 245 patients allocated to thrombolytic therapy. Patency of the infarct-related artery was achieved in 181 patients (85%). Enzymatic infarct size, measured from cumulative alpha-hydroxybutyrate dehydrogenase release, was smaller in patients allocated to thrombolytic therapy (median 760 versus 1,179 U/liter in control subjects, p = 0.0001). Left ventricular ejection fraction measured by radionuclide angiography before discharge was higher after thrombolytic therapy (median 50% versus 43% in control subjects, p = 0.0001). Twelve month mortality was lower in patients allocated to thrombolytic therapy (8% versus 16% in the control group, p less than 0.01). In multivariate regression analysis infarct size limitation, improvement of left ventricular ejection fraction and 3 month mortality were predicted by sigma ST, time from onset of symptoms to admission and Killip class at admission. Thrombolysis was most useful in patients admitted within 2 hours after onset of symptoms and in patients with a sigma ST segment of 1.2 mV or more. On the other hand, no beneficial effects of streptokinase on enzymatic infarct size, left ventricular function or mortality were observed in the subset of patients with sigma ST less than 1.2 mV, admitted 2 to 4 hours after onset of symptoms.     

Efficacy of percutaneous transluminal coronary recanalization utilizing streptokinase thrombolysis in patients with acute myocardial infarction

Since coronary thrombosis is a principal factor in the evolving necrotic process in the majority of patients with acute myocardial infarction (AMI), a prospective study was conducted in 25 AMI patients who underwent expeditious coronary arteriography. Of these patients, 22 with totally occluding thrombus also received early streptokinase (STK) administration. STK was given by intracoronary (20 patients) or systemic (two patients) infusion, 2000 to 50,000 IU/min, to a total dose of 125,000 to 500,000 IU within 10 hours of AMI symptom onset. Eighteen patients had angiographically visualized successful coronary thrombolysis; the shorter the interval between onset of symptoms to treatment, the more rapid was the clot dissolution. Successful thrombolysis occurred concomitantly with readily managed reperfusion ventricular tachyarrhythmias in nearly all patients. In addition, STK recanalization resulted in relief of ongoing chest pain in 10 of 12 patients, 10 of 16 evidenced immediate normalization of hyperacute ST segment abnormalities, and 8 of 14 demonstrated subsequent improvement of angiographically visualized left ventricular (LV) ejection fraction. In the percutaneous transluminal coronary recanalization (PTCR) procedure, the step of using a soft-tipped guide wire itself was transiently useful in only one of seven patients in whom this was attempted; reocclusion took place without added STK therapy. Nitroglycerin (NTG) alone produced only slight distal patency in but 1 of 19 patients with coronary occlusion given the nitrate. Importantly, in 14 control AMI patients receiving conventional treatment without STK, 10 showed angiographically complete occlusion of the coronary artery supplying the infarct region 1 month after infarction, thereby excluding spontaneous clot lysis mimicking STK-PTCR-induced reperfusion. These data support the concept that coronary occlusion by thrombosis is inherently involved with AMI and that rapid PTCR application of intracoronary STK provides potent thrombolysis, superior to that provided by NTG and guide wire passage in reestablishing coronary flow with attendant salvage of jeopardized myocardium and with subsequently improved LV function.     

Free radical activity and left ventricular function after thrombolysis for acute infarction.

BACKGROUND--Experimental data suggest that reperfusion injury involving free radicals contributes to the impairment of left ventricular function after successful thrombolysis. METHODS--In 72 patients presenting with acute myocardial infarction, markers of free radical activity were measured before streptokinase and two hours later. Thiobarbituric acid reactive material (TBA-RM) reflects lipid peroxidation by free radicals, and the concentration of plasma total thiols (34 patients) reflects oxidative stress. Coronary arteriography was performed at 18-72 hours after thrombolysis to determine coronary patency, and left ventricular function was assessed by ventriculography and from QRS scoring of the electrocardiogram. RESULTS--The infarct related artery was patent (Thrombolysis In Myocardial Infarction Trial grade 2 or better) in 60 (83%) and occluded in 12. In the 60 with a patent artery, the concentration of TBA-RM increased after streptokinase by (mean (SD)) 9.2 (14.0) nmol/g albumin, whereas in the 12 with an occluded artery TBA-RM decreased by 7.0 (11.3) nmol/g albumin (p < 0.01 between groups). In those with a patent artery the rise in TBA-RM associated with thrombolysis correlated with left ventricular ejection fraction (R = -0.41, p < 0.002), and with the QRS score (R = +0.38, p = 0.003). Plasma total thiol concentrations decreased by 12.7 (31.1) mumol/l in those with a patent artery, and this decrease associated with thrombolysis correlated with left ventricular ejection fraction (R = +0.39, p < 0.02) but not with the QRS score (R = -0.2, NS). CONCLUSIONS--These findings suggest that reperfusion injury mediated by free radicals may be of clinical importance in humans.     

The Italian Group for the Study of Streptokinase in Myocardial Infarct: Coronarographic and ventriculographic study

The effects of intravenous thrombolytic treatment on the reperfusion of infarct related coronary artery and left ventricular function were assessed in 251 pts. with first episode of myocardial infarction, enrolled in the G.I.S.S.I. trial, in which coronary angiography and left ventriculography have been performed within the second and third week from the onset of symptoms. A total of 251 pts. were randomized in two groups--133 treated with streptokinase (SK) and 118 controls. Among those treated with SK, in 71 (57.9%) the treatment was started within 3 hours and in 56 (42.1%) after 3 hours from the onset of symptoms. The infarct related vessel was occluded in 43 (32.3%) patients treated and in 60 (50.9%) controls (p less than 0.01). No significant difference was found in the left ventricular ejection fraction among the treated patients and controls while a significant difference resulted in the percentage of patients who had left ventricular ejection fraction greater than or equal to 50% in the group of patients with SK within 3 hours in comparison to controls. Left ventricular ejection fraction remained normal without any correlation with the type and time of the treatment, if the infarct related vessel resulted open at the coronary angiography. The study of the regional wall motion of left ventricle did not show any significant difference neither in the infarct size nor in the type and the time of treatment. In conclusion, the thrombolitic treatment with SK in acute myocardial infarction using the protocol adopted in the G.I.S.S.I. trial, obtains the reopening of infarct related vessel in an high percentage of patients; this event helps in great measure to conserve left ventricular function, especially in patients with anterior myocardial infarction if the treatment was started within the first 3 hours from the onset of symptoms.