Intracoronary versus intravenous streptokinase in acute myocardial infarction

To assess the relative efficacy of coronary thrombolysis using intracoronary versus intravenous streptokinase, 32 patients with acute myocardial infarction were randomly assigned to receive intracoronary (n = 17) and intravenous streptokinase (n = 15). All patients underwent selective coronary arteriography before and after administration of streptokinase by either route within 4 hours of the onset of symptoms. Intravenous streptokinase was given as 750,000 units over 30 minutes, while a mean dose of 180,000 units was required for thrombolysis in the group having intracoronary delivery. Recanalization occurred in 71.4% (10 of 14) of patients receiving streptokinase, by the intracoronary group in contrast to only 25% of patients (3 of 12) who received the drug intravenously (P less than 0.05). Spontaneous thrombolysis was seen in 17.6% and 20% of the patients in the groups having intracoronary and intravenous delivery, respectively. Bleeding complications were few in both groups. Thus, when baseline coronary arteriography is performed, recanalization with intracoronary streptokinase is more effective in the treatment of acute myocardial infarction than intravenous streptokinase.     

Thrombolytic therapy of acute myocardial infarction

Thrombotic coronary artery occlusion is now recognized as the usual cause of acute myocardial infarction. The thrombus usually forms at the site of intimal disruption over an atherosclerotic plaque. Following coronary occlusion, myocardial necrosis begins within 40 minutes in the subendocardium and progresses outward toward the epicardium over the next several hours. The intracoronary infusion of streptokinase will produce lysis of the occluding thrombus in up to 80% of patients. It appears that reperfusion with streptokinase in the first few hours following the onset of the myocardial infarction produces a small increase in late left ventricular function, though ECG and enzyme evidence of acute myocardial infarction are not prevented. The improvement in left ventricular function is variable from patient to patient and has not been demonstrated in all the randomized studies to date. The time limit for myocardial salvage may not be the same in all patients. The greatest benefit is probably achieved with reperfusion in the first 4-6 hours, although some benefit may occur as late as 18 hours after the onset of infarction. Many patients who receive intracoronary infusion of streptokinase develop a systemic lytic state, though serious bleeding complications in carefully selected patients are infrequent. High-dose IV streptokinase is easier, cheaper, and quicker to initiate than intracoronary streptokinase but is probably less effective than the intracoronary route in producing rapid lysis of the occluding coronary thrombus. The optimal dose and rate of administration of IV streptokinase have not been determined. The final role and ultimate benefit of thrombolytic therapy of myocardial infarction have not yet been determined, but some of the issues may be clarified by the larger randomized trials now under way. It appears, at present, that the use of intracoronary streptokinase may have a role in the treatment of selected patients with acute myocardial infarctions in institutions with the facilities and the personnel necessary to perform this procedure safely. In the future, thrombolytic therapy may also have a place in the treatment of selected patients with unstable angina and post-myocardial infarction angina. The future availability of more selective thrombolytic agents may make the early IV therapy of myocardial infarction a safer, more effective option and expand the indications for thrombolytic therapy.     

Effect of intracoronary streptokinase infusion and verapamil treatment on the size of the affected area in myocardial infarct patients

The effect of intracoronary streptokinase administration (31 patients), verapamil treatment (23 patients) and conventional therapy (27 patients) on the size of the affected area was examined in patients with acute myocardial infarction (MI). Streptokinase was administered in a dose of 250,000-500,000 IU within the first 3 to 20 hours of myocardial infarction, and verapamil, 360 to 400 mg, daily within the first 5 to 12 hours of the attack. The occluded coronary artery was recanalized in response to streptokinase administration in 21 patients. Serial measurements of CPK activity and serum myoglobin levels, and electrocardiographic precordial cartograms demonstrated a reduction in MI size following streptokinase administration. Verapamil had no basic effect on the final size of myocardial lesion, although it improved somewhat the clinical course of the disease.     

Relation of effectiveness of intracoronary thrombolysis in acute myocardial infarction to systemic thrombolytic state

Twenty-nine patients received intracoronary thrombolytic therapy for acute myocardial infarction 3.5 +/- 1.4 hours (mean +/- standard deviation) after the onset of pain. Ten patients received urokinase (UK) and 19 patients received streptokinase (SK). Laboratory variables of the coagulation system were measured before and immediately after therapy. When comparing patients in whom coronary artery recanalization occurred vs those in whom the artery remained occluded, those in whom recanalization was achieved had greater alterations in fibrinogen, prothrombin time, activated partial thromboplastin time, fibrin/fibrinogen degradation products and plasminogen by thrombolytic therapy than did those in whom recanalization was not achieved (p less than 0.05 for all variables). Euglobulin lysis time showed a similar but nonsignificant trend (p = 0.114). Patients who received SK showed markedly greater alterations in coagulation parameters than did patients treated with UK (p less than 0.05 for 5 of 6 variables measured) and had a much higher incidence of successful thrombolysis (74% for SK, 20% for UK). These data indicate that the development of a systemic fibrinolytic state contributes to success when using intracoronary thrombolytic agents in acute myocardial infarction. Rather than being considered an adverse effect of therapy, a systemic lytic state may serve as a reasonable clinical goal in attempting to produce thrombolysis.     

Intravenous versus intracoronary streptokinase for acute transmural myocardial infarction

In order to compare the thrombolytic efficacy of selective versus systemic administration of streptokinase, we gave this drug by either the intracoronary or intravenous routes to 25 patients during the first 6 hours of acute myocardial infarction. All patients had total occlusion of the infarct-related vessel, unresponsive to intracoronary nitroglycerin. Twelve patients received intravenous streptokinase and 13 received intracoronary administration of the drug. Angiograms were taken prior to and during streptokinase administration. Reopening was achieved in 11 of 13 intracoronary patients and 8 of 12 intravenous patients (P = Ns). Time to reopening was longer (54 minutes) in the intravenous patients than in the intracoronary patients (26 minutes) (P < 0.05). In this study, intravenous streptokinase reopened infarct-related vessels nearly as often as intracoronary streptokinase, but it took longer. Given the limited access and time to prepare for intracoronary infusion and the ease of intravenous administration, further study of intravenous streptokinase is justified.     

Prospective randomized trial of intravenous and intracoronary streptokinase in acute myocardial infarction

To evaluate the relative thrombolytic efficacy and complications of intracoronary vs high-dose, short-term intravenous streptokinase infusion in patients with acute myocardial infarction, we performed baseline coronary arteriography and then randomly allocated 51 patients with acute myocardial infarction to receive either intracoronary (n = 25) or intravenous (n = 26) streptokinase. Patients getting the drug by the intracoronary route received 240,000 IU of streptokinase into the infarct-related artery over 1 hr, whereas those getting the drug by the intravenous route received either 500,000 IU of streptokinase over 15 min (n = 10) or 1 million IU of streptokinase over 45 min (n = 16). Angiographically observed thrombolysis occurred in 76% (19/25) of the patients receiving intracoronary streptokinase, in 10% (1/10) of the patients receiving 500,000 IU of streptokinase intravenously, and in 44% (7/16) of the patients receiving 1 million IU of streptokinase intravenously. Among patients in whom thrombolysis was observed, mean elapsed time from onset of streptokinase infusion until lysis was 31 +/- 18 min in patients receiving intracoronary streptokinase and 38 +/- 20 min in those receiving intravenous streptokinase (p = NS). Among patients in whom intravenous streptokinase "failed," intracoronary streptokinase in combination with intracoronary guidewire manipulation recanalized only 7% (1/15). Fibrinogen levels within 6 hr after streptokinase were significantly lower in the patients receiving intravenous streptokinase (39 +/- 17 mg/dl) than the levels in those receiving intracoronary streptokinase (88 +/- 70 mg/dl) (p less than .05) but were similar 24 hr after streptokinase in the two groups. Bleeding requiring transfusion occurred in one patient in each group. Thus, in this prospective randomized trial of intracoronary vs intravenous streptokinase, hemorrhagic complications were few, although both regimens produced a systemic lytic state. Although the thrombolytic efficacy of intracoronary streptokinase was superior to that of high-dose, short-term intravenous streptokinase, the higher-dose intravenous regimen (1 million IU over 45 min) achieved thrombolysis in a significant minority (44%) of patients and might be useful therapy for patients not having access to emergency catheterization.     

Comparison of intravenous anisoylated plasminogen streptokinase activator complex and intracoronary streptokinase in acute myocardial infarction

Coronary angiography was used to compare the efficacy of anisoylated plasminogen streptokinase activator complex (APSAC) administered intravenously and streptokinase given by intracoronary infusion in inducing reperfusion in patients with a proven acute myocardial infarction. Forty-two patients received 30 U of APSAC intravenously over 5 minutes and 43 patients received 250,000 IU of streptokinase given via intracoronary infusion over 90 minutes, after occlusion of the infarct-related vessel was demonstrated by angiography. Reperfusion was achieved in 23 (64%) of 36 patients (mean time to reperfusion 46 minutes) treated with APSAC and 25 (67%) of 37 patients (mean time to reperfusion 45 minutes) treated with intracoronary streptokinase, who were angiographically evaluated 90 minutes after the start of treatment. Twenty-four hours after treatment, reocclusion had occurred in 1 (5%) of 22 patients in the APSAC group and in 3 (13%) of 23 patients in the streptokinase group. No major bleeding was observed in either treatment group despite a similar systemic lytic state that lasted for up to 48 hours. Two patients treated with APSAC died after severe left ventricular failure unrelated to therapy. The results indicate that APSAC given intravenously is as effective as streptokinase given intracoronary in producing thrombolysis in acute myocardial infarction. The major advantages of APSAC are its rapid and convenient administration by a single intravenous injection, the low rate of arterial reocclusion and good patient tolerance.     

Intravenous streptokinase in acute myocardial infarction

Intravenous (IV) fibrinolytic therapy, a recent area of research, has a great deal of applicability in emergency medicine. We report our experience with 30 patients treated with this method. Thirty consecutive patients in the early stages of acute evolving myocardial infarction (AMI) were assigned to receive high-dose IV streptokinase, 1.5 million units over a 30-minute period. Patients presented to the treating hospital at a mean time of 1.21 +/- 1.08 hours, and treatment commenced at a mean time of 2.77 +/- 1.31 hours after the onset of symptoms. Using standard clinical criteria, 86.7% (n = 26) of the patients reperfused initially. Two, however, reoccluded within the first 48 hours, and their clinical symptoms of myocardial infarction reappeared. By clinical observation 80% (n = 24) of the patients reperfused, and myocardial salvage was observed. Twenty-four patients with clinical reperfusion and one additional patient had patency of the affected artery, yielding a reperfusion rate of 83.3% (n = 25) as judged by angiography within one week of AMI. Both patients who had reoccluded clinically also were found to be occluded on angiography. Clinical and angiographic methods yield very similar results for the judgment of reperfusion (80% vs 83%, respectively, with no significant difference, P not significant). The results of our study tend to confirm the efficacy of IV streptokinase as a valuable management tool for early myocardial infarction.     

Late results of reperfusion with intracoronary streptokinase

Intracoronary streptokinase was infused to 152 randomly selected patients after acute myocardial infarction (MI). Control group consisted of 150 randomly selected patients after MI who were treated by conventional methods. Preliminary results indicate several beneficial effects of early reperfusion with intracoronary streptokinase.     

Influence of thrombolytic therapy on the incidence of left ventricular thrombi after acute anterior myocardial infarction: role of successful reperfusion.

BACKGROUND: Previous studies have reported controversial results regarding the effectiveness of systemic thrombolysis in preventing left ventricular (LV) thrombus after acute myocardial infarction (MI). HYPOTHESIS: This study was performed to evaluate the influences of thrombolysis, and particularly successful reperfusion, on the incidence of LV thrombus formation after acute anterior MI. METHODS: In all, 191 patients suffering from a first attack of acute anterior MI were prospectively evaluated by two-dimensional echocardiography and coronary angiography, performed at the end of the first week and within the first two weeks of MI, respectively. Of these, 98 who presented within 12 h of onset of symptoms received intravenous streptokinase (1.5 million IU), while the remaining 93 patients who, either because of contraindications or late admission, did not receive thrombolytic treatment served as control group. All patients received aspirin and full-dose anticoagulation with intravenous heparin. Successful reperfusion in the streptokinase group was assessed by enzymatic and electrocardiographic evidence. RESULTS: The overall incidence of LV thrombi was 24.6% (47/191). When all patients were evaluated, no statistically significant difference was found between the frequency of LV thrombi in the patients who had thrombolysis (22.4%) and those who did not (26.8%), despite a trend toward the formation of fewer thrombi in the initial group (p > 0.05). However, the patients who had successful reperfusion with streptokinase (n = 64) had significantly reduced incidence of LV thrombi compared with those who did not receive thrombolytic therapy (20 vs. 26.8%, p < 0.05). Stepwise multivariate analysis suggested that LV abnormal wall motion score (p = 0.01) and presence of LV aneurysm were independent predictors of LV thrombus formation in patients with acute anterior MI. CONCLUSION: Not all patients who received streptokinase for acute anterior MI, but only those with successful reperfusion had reduced incidence of LV thrombi. The favorable effects of thrombolysis on LV thrombus formation are probably due to the preservation of global LV systolic function.     

Late effects of intracoronary streptokinase on regional wall motion, ventricular aneurysm and left ventricular thrombus in myocardial infarction: results from the Western Washington Randomized Trial

To determine whether intracoronary streptokinase improves late regional wall motion or reduces left ventricular aneurysm or thrombus formation in patients with acute myocardial infarction, two-dimensional echocardiography was performed at 8 +/- 3 weeks after infarction in 83 patients randomized to streptokinase (n = 45) or standard therapy (n = 38) in the Western Washington Intracoronary Streptokinase Trial. Among the patients treated with streptokinase, the average time to treatment was 4.7 +/- 2.5 hours after the onset of chest pain, and 67% had successful reperfusion. Regional wall motion was assessed in nine left ventricular segments on a scale of 1 to 4 (normal, hypokinetic, akinetic and dyskinetic). Left ventricular thrombus formation was interpreted as positive, equivocal or negative. All patients received anticoagulant therapy in the hospital and 52 received such therapy after hospital discharge. The mean (+/- SD) global (1.5 +/- 0.4 in both groups) and regional wall motion scores in the streptokinase-treated and control groups were not significantly different. The prevalence of aneurysm was 16% in both groups. Left ventricular thrombus was identified in only five patients (positive identification in four, and equivocal in one), all in the streptokinase-treated group (p = NS). There were also no differences between streptokinase and control treatment in any of the echocardiographic variables in subgroups of patients with anterior infarction, inferior infarction, no prior infarction or reperfusion with streptokinase. It is concluded that intracoronary streptokinase given relatively late in the course of acute myocardial infarction does not result in improved global or regional wall motion or a reduction in left ventricular thrombus or aneurysm formation in survivors studied 2 months after myocardial infarction.     

Contemporary management of ST elevation myocardial infarction

Management of acute ST elevation myocardial infarction (MI) has become increasingly complex. Third-generation fibrinolytic agents have provided simpler bolus administration and enhanced arterial patency rates but have not lowered mortality. Prehospital fibrinolysis reduces time to treatment, and studies continue to better define the clinical benefits. Combining glycoprotein (GP) IIb/IIIa inhibitors with reduced-dose fibrinolytic therapy thus far has not reduced mortality; improvements in secondary outcomes such as recurrent infarction have been offset by increases in bleeding complications, particularly in elderly patients. In contrast to fibrinolytic trial results, outcomes are improved in patients who promptly undergo primary percutaneous coronary intervention (PCI). Meta-analyses demonstrate a significant reduction in mortality compared with patients who receive fibrinolytic therapy. Accessibility of primary intervention remains an important limitation, although recent trials suggest superiority of intervention even when hospital transfer is necessary. Conflicting trends include the development of regional centers for interventional treatment of MI as well as the dissemination of limited interventional programs to smaller hospitals. Facilitated PCI, a hybrid of pharmacological reperfusion (typically combination therapy) followed by intervention, may bridge the delay when primary intervention is not immediately available. Optimal therapy for acute MI must be individualized based on both patient characteristics and resource availability.     

Clinical perspectives and therapeutics of thrombolysis

Reperfusion therapy with thrombolytic agents has been a significant advancement in the management of patients with acute ST elevation myocardial infarction. The outcome of acute myocardial infarction has significantly improved by early application of thrombolytic therapy. Intracoronary streptokinase has been used for >30 years, but reawakening interest occurred in the early 1980s in the use of thrombolytic therapy to establish rapid reperfusion during an acute myocardial infarction. Initial studies aimed at direct intracoronary thrombolysis, but owing to its cumbersome process and requirement of an active round the clock cardiac catheterization laboratory, it has been replaced by regimens of intravenous thrombolytic therapy which is as efficacious as intracoronary administration. Consideration of thrombolytic therapy has become a standard treatment for patients presenting with acute ST elevation myocardial infarction and various well-controlled trials have demonstrated the importance of both early and full reperfusion in improving clinical outcome in the setting of acute myocardial infarction. The subject of intravenous thrombolysis is perhaps the most rapidly evolving area in the management of acute myocardial infarction patients in the past decade. The current review focuses on the thrombolysis in the treatment of myocardial infarction and other conditions.     

Exercise 2-dimensional echocardiography. Quantitation of left ventricular performance in patients with severe angina pectoris

Although intracoronary thrombus formation plays a major role in acute transmural myocardial infarction (MI), its occurrence in unstable angina (UA) and nontransmural MI has not clearly been established. To determine whether intracoronary thrombus does occur in these syndromes, coronary arteriography was performed before, during, and after intracoronary nitroglycerin and streptokinase infusion in 17 patients. None of the 8 patients with nontransmural MI and 1 of the 9 patients with UA responded to intracoronary nitroglycerin. Seven of 8 patients with nontransmural MI and 4 of 9 patients with UA responded to streptokinase infusion with opening of an occluded vessel, an increase in stenotic diameter, dissolution of an intracoronary filling defect, or a combination of these. Serial opening and closing of ischemia-related vessels occurred spontaneously and in response to streptokinase in some patients in whom thrombolysis was demonstrated. Evidence of thrombolysis was not seen in any patient studied longer than 1 week from the onset of the rest pain syndrome. The finding of thrombolysis in several patients with nontransmural MI and UA suggests that intracoronary thrombus formation plays a pathogenetic role in some patients with these ischemic syndromes.     

Reduction of congestive heart failure symptoms by very early fibrinolytic therapy in acute myocardial infarction: a long-term follow-up

BACKGROUND: In patients with acute myocardial infarction (MI), early fibrinolytic therapy results in improved survival and preservation of ventricular function. The purpose of the study was to determine whether very early treatment also reduces the development of congestive heart failure. METHODS AND RESULTS: During the years 1984 to 1989, 358 consecutive patients with acute MI were treated with streptokinase, 161 within the first 1.5 hours from the onset of chest pain (group A) and 197 within 1.5 to 4.0 hours (group B). In 68, fibrinolysis was initiated in the prehospital setting pioneered by our group. Symptoms related to heart failure including dyspnea on exertion, fatigue, orthopnea, paroxysmal nocturnal dyspnea, nocturia, and peripheral edema, in addition to pulmonary edema events, were assessed during 5 years of follow-up. The evaluation was based on medical records and a detailed questionnaire, which was filled in by the investigators. A favorable significant effect of very early thrombolysis on the development of most of these limiting symptoms appeared 3 months after hospital discharge and persisted thereafter (P <.05). During hospitalization, pulmonary edema attacks occurred less frequently in patients from group A (23% vs 36.5%, P <.01). This difference persisted during 4 years of follow-up (13% vs 36%, P <.001). CONCLUSIONS: Our data demonstrate that very early fibrinolytic therapy results in a significant long-term reduction of congestive heart failure-related symptoms and thereby improves the quality of life in patients after MI.     

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.     

Coronary thrombolysis with clot-selective plasminogen activators

Coronary thrombolysis is at present intensively investigated in the treatment of acute myocardial infarction. One line of research focuses on the development of new, fibrin-specific agents which might induce more clot-selective thrombolysis than streptokinase and urokinase. Clot-selective thrombolytic agents preferentially activate fibrin-bound plasminogen and, thereby, minimize the generation of free circulating plasmin which is responsible for the hemostatic breakdown and bleeding risk. Intravenous administration of fibrin-specific thrombolytic agents has two major advantages over intracoronary administration: firstly, infusion is more easily and widely applicable and secondly, therapy may be initiated more rapidly, which is important for the early restoration of nutritional blood flow and salvage of functional myocardial tissue. Three clot-selective thrombolytic agents are presently investigated for coronary thrombolysis. Impressive reopening rates have been reported with acylated streptokinase-plasminogen complex, but unfortunately, its use was associated with extensive systemic fibrinolytic activation and bleeding complications. Pro-urokinase, the single chain precursor of urokinase, exhibited intrinsic, fibrin-specific thrombolytic activity in vitro and in animal models but no human trials have yet been reported. At present, the largest clinical experience has been obtained with tissue-type plasminogen activator (t-PA). After small-scale pilot studies with t-PA obtained from cell culture media, larger clinical trials have now been performed using t-PA obtained by recombinant DNA technology (rt-PA). In the first study, intravenous infusion of rt-PA in patients with acute myocardial infarction yielded a recanalization rate of about 75% without clinically relevant systemic activation of the fibrinolytic system in most patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Thrombolytic therapy in acute myocardial infarction: Review of clinical trials

Intracoronary infusion of streptokinase is associated with recanalization rates of 60 to 90% immediately after the procedure. Mortality data in published trials are conflicting. In 125 registry patients who had paired contrast ventriculograms before streptokinase infusion and hospital discharge, improvement in ejection fraction correlated with incomplete coronary obstruction before angiography, the presence of collateral vessels to the infarct area and recanalization of complete obstruction. In assessing the risk/benefit ratio of intracoronary streptokinase infusion, the risks of angiography in the setting of acute myocardial infarction, reocclusion, bleeding and such secondary interventions as angioplasty or bypass surgery must be considered. Intravenous infusion of conventional doses of streptokinase was associated with improved survival in some trials in which therapy began within 12 hours after the onset of infarction. Immediate recanalization rates in patients who received large doses of intravenous streptokinase were lower than those associated with intracoronary streptokinase infusion. The risks and benefits of high-dose intravenous streptokinase administration must still be assessed.     

Prevention of subsequent exercise-induced periinfarct ischemia by emergency coronary angioplasty in acute myocardial infarction: comparison with intracoronary streptokinase

To compare the efficacy of emergency percutaneous transluminal coronary angioplasty and intracoronary streptokinase in preventing exercise-induced periinfarct ischemia, 28 patients presenting within 12 hours of the onset of symptoms of acute myocardial infarction were prospectively randomized. Of these, 14 patients were treated with emergency angioplasty and 14 patients received intracoronary streptokinase. Recatheterization and submaximal exercise thallium-201 single photon emission computed tomography were performed before hospital discharge. Periinfarct ischemia was defined as a reversible thallium defect adjacent to a fixed defect assessed qualitatively. Successful reperfusion was achieved in 86% of patients treated with emergency angioplasty and 86% of patients treated with intracoronary streptokinase (p = NS). Residual stenosis of the infarct-related coronary artery shown at predischarge angiography was 43.8 +/- 31.4% for the angioplasty group and 75.0 +/- 15.6% for the streptokinase group (p less than 0.05). Of the angioplasty group, 9% developed exercise-induced periinfarct ischemia compared with 60% of the streptokinase group (p less than 0.05). Thus, patients with acute myocardial infarction treated with emergency angioplasty had significantly less severe residual coronary stenosis and exercise-induced periinfarct ischemia than did those treated with intracoronary streptokinase. These results suggest further application of coronary angioplasty in the management of acute myocardial infarction.     

Development and Pathophysiological Basis of Thrombolytic Therapy in Acute Myocardial Infarction Part II. 1977-1980 The Pathogenetic Role of Thrombus Is Established by the Goettingen Pilot Studies of Mechanical Interventions and Intracoronary Thrombolysis in Acute Myocardial Infarction

Between 1977 and 1980, our group performed immediate coronary angiography in 158 patients admitted with acute myocardial infarction (MI) at the University of Goettinger, Germany. From June 1978 to May 1979, our pioneering study of mechanical transcatheter recanalization of acute total coronary artery occlusions using guidewires and tapered catheters was performed. Restoration of antegrade flow in 7 of 13 patients was associated with an improvement in left ventricular function not seen in historical controls. From June 1979 to December 1980, the pathogenetic role of thrombus and spasm in acute coronary syndromes was explored in our pioneering study of intracoronary streptokinase infusion. Following injection of nitroglycerin, streptokinase was selectively infused at a rate of 2000 U/minute for 50–95 minutes. Only four of the initial 22 infarct patients showed improvement of antegrade flow following intracoronary nitroglycerin alone. Reopening of the completely obstructed vessel or increase in lumen diameter at the site of subtotal occlusion occurred in 22 of 29 infarct patients within 15–90 minutes of streptokinase infusion but in none of the five patients with unstable angina. Chest pain was alleviated and left ventricular function was improved significantly after successful lysis. The first presentation of both our mechanical and pharmacological interventions in acute MI to a large international audience at the annual American Heart Association meeting in 1979 convinced clinicians of the etiologic role of fibrin-rich coronary thrombus in acute MI. The demonstration of rapid restoration of antegrade flow initiated a worldwide renaissance in the application of thrombolytic therapy and paved the way for primary angioplasty in acute MI.