Systemic versus intracoronary streptokinase infusion in the treatment of acute myocardial infarction

Clinically encouraging results can be obtained with an intravenous high dose short-time infusion of streptokinase in patients with evolving myocardial infarction. The feasibility and efficacy of the intracoronary and the systemic approach of streptokinase therapy in acute myocardial infarction are discussed in this report and include topics such as infarct artery recanalization success rate, coronary thrombus lysis time, benefit for patients with subtotal coronary occlusion, reocclusion rate, the necessity of additional surgical interventions, salvage of ischemic myocardium and side effects. The value of high dose intravenous short-time streptokinase infusion needs to be assessed with properly designed clinical trials against the background afforded by the results observed with direct intracoronary streptokinase infusion.     

Development and Pathophysiological Basis of Thrombolytic Therapy in Acute Myocardial Infarction: Part IV

Acute and day 10 to 14 recanalization rates with intracoronary thrombolytic and/or spasmolytic therapy were determined in the First Mt. Sinai-N.Y.U. Reperfusion Trial (1984). Recanalization of total occlusion was accelerated by intracoronary streptokinase, the first proven potentially beneficial effect of thrombolytic therapy. Intravenous administration of thrombolytic agents, including t-PA, was less effective in accelerating recanalization than intracoronary streptokinase as assessed by 90-minute rates of TIMI-III flow. In clinical practice the greater ease of intravenous administration outweighed this disadvantage, but intracoronary administration was uniquely suited to analyze the pathophysiological principles of reperfusion therapy. The first randomized trial (n = 533) to establish the benefits of early reperfusion, the Netherlands Randomized Trial, achieved infarct vessel patency in 85% of patients within 200 minutes of symptom onset by administering intracoronary streptokinase alone or following a rapid intravenous infusion of streptokinase. Ejection fraction improved significantly and mortality at 28 days was reduced (6% vs 12%). The ISIS-2 Trial (1988) showed mortality reduction with intravenous thrombolytic therapy up to 24 hours after infarct onset, but did not explain the benefit of late reperfusion. In the Second Mt. Sinai-N.Y.U. Reperfusion Trial (1989; n = 393), intracoronary streptokinase administered 4 to 14 hours after infarct onset increased thallium uptake. Streptokinase improved ejection fraction in patients with collateralized total occlusion but not in those with noncollateralized total occlusion. Preintervention antegrade flow was associated with ejection fraction improvement regardless of treatment assignment. We concluded that thrombolytic therapy after > 4 hours of infarction salvages myocardium in patients with collateralized total coronary artery occlusion. Total coronary occlusion was associated with collateral flow in 33% at acute angiography, but in 90% at day 10 to 14 angiography, indicating a second phase of collateral growth. An angioplasty model was developed to assess appearance and disappearance of collateral flow immediately after controlled coronary occlusion and reflow in humans. Using this model we demonstrated limitation of ischemia by collateral recruitment prospectively.     

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.     

Reperfusion arrhythmia: a marker of restoration of antegrade flow during intracoronary thrombolysis for acute myocardial infarction

We studied the effects of coronary recanalization on arrhythmogenesis in patients undergoing intracoronary thrombolysis during the early hours of myocardial infarction. Catheterization, ventriculography, coronary angiography, and intracoronary streptokinase infusion were performed in 22 patients. Twenty-one of 22 had thrombotic total occlusion of the infarct-related transient thrombolysis with reocclusion by the end of the procedure. In 12 of these 17 patients, restoration of antegrade coronary flow was accompanied by transient arrhythmia. In these 12 patients coronary angiography within seconds of onset of arrhythmia showed vessel patency in a previously totally occluded coronary artery. Two additional patients developed arrhythmias during streptokinase infusion but after reperfusion had already been established. Accelerated idioventricular rhythm was most often noted. Sinus bradycardia and atrioventricular block with hypotension occurred during restoration of flow in arteries supplying the inferoposterior left ventricle. These arrhythmias may be useful noninvasive markers of successful reperfusion during thrombolytic therapy in acute myocardial infarction.     

Percutaneous transluminal coronary recanalization: Procedure,results, and acute complications

Percutaneous transluminal coronary recanalization, a new therapeutic procedure used in acute myocardial infarction, offers significant reduction in mortality, as well as more effective limitation of the zone of infarction than has been possible with other pharmacologic treatment employed in the past. The risk of coronary angiography during acute myocardial infarction was surprisingly low, as was the risk of hemorrhagic complications following the intracoronary administration of relatively low doses of thrombolytic substances such as streptokinase. Mechanical recanalization was possible in about one fifth of patients and successful in approximately half of all such attempts, but complications occurred in a small percentage of attempts at this step. Coronary artery spasm was excluded as a possible cause of occlusion in almost all cases. Selective intracoronary infusion of streptokinase produced the highest degree of myocardial reperfusion, and best results were achieved when therapy was initiated shortly after thrombotic occlusion occurred. Residual stenosis of more than 75% luminal diameter narrowing was present in approximately three fourths of cases after complete thrombolysis, and the majority of patients remained appropriate candidates for coronary bypass surgery or for percutaneous transluminal coronary angioplasty (Grüntzig procedure). Although complete analysis of the efficacy of selective recanalization was difficult because it was not possible to establish a suitable control group for purposes of comparison, the mortality of less than 1% in the present group of 232 patients within the first 6 hours following myocardial reperfusion provides an encouraging result.     

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.     

Coronary angiographic morphology in myocardial infarction: a link between the pathogenesis of unstable angina and myocardial infarction

It has previously been shown that analysis of coronary morphology can separate unstable from stable angina. An eccentric stenosis with a narrow neck or irregular borders, or both, is very common in patients who present with acute unstable angina, whereas it is rare in patients with stable angina. To extend these observations to myocardial infarction, the coronary morphology of 41 patients with acute or recent infarction and nontotally occluded infarct vessels was studied. For all patients, 27 (66%) of 41 infarct vessels contained this eccentric narrowing, whereas only 2 (11%) of 18 noninfarct vessels with narrowing of 50 to less than 100% had this lesion (p less than 0.001). In addition, a separate group of patients with acute myocardial infarction who underwent intracoronary streptokinase infusion were also analyzed in similar fashion. Fourteen (61%) of 23 infarct vessels contained this lesion after streptokinase infusion compared with 1 (9%) of 11 noninfarct vessels with narrowing of 50 to less than 100% (p less than 0.01). Therefore, an eccentric coronary stenosis with a narrow neck or irregular borders, or both, is the most common morphologic feature on angiography in both acute and recent infarction as well as unstable angina. This lesion probably represents either a disrupted atherosclerotic plaque or a partially occlusive or lysed thrombus, or both. The predominance of this morphology in both unstable angina and acute infarction suggests a possible link between these two conditions. Unstable angina and myocardial infarction may form a continuous spectrum with the clinical outcome dependent on the subsequent change in coronary supply relative to myocardial demand.     

Quantitative coronary angiography during intracoronary streptokinase in acute myocardial infarction: how long to continue thrombolytic therapy?

An intracoronary infusion of streptokinase is often administered in patients with acute myocardial infarction. To address the question of how long intracoronary streptokinase should be infused, we studied 13 patients with symptoms and electrocardiographic findings suggesting an evolving myocardial infarction. We used subselective catheterization techniques and made quantitative angiographic measurements of the percentage of reduction of coronary artery (CA) diameter before intracoronary streptokinase therapy, immediately after reperfusion was established, and at the completion of streptokinase infusion. Before intracoronary streptokinase and after intracoronary nitroglycerin, nine patients had 100% obstruction of the CA in the "infarct-related vessel." In seven patients reperfusion was established (25 +/- 21 min, mean +/- SD) at which time CA diameter was reduced by 77 +/- 22%. The streptokinase infusion was then continued until repeated films (every 10 to 15 min) suggested no further change at the site of CA obstruction (93 +/- 68 min). The percentage of CA diameter reduction when streptokinase infusion was discontinued was 55 +/- 32%; this value was less (P less than 0.05) than that observed early after reperfusion. These data show that after initial reperfusion was achieved by the use of intracoronary streptokinase, additional streptokinase lessened the reduction of CA diameter. Residual thrombus may be present at the narrowed CA site early after reperfusion, and further "cleanup" can be achieved by prolonging streptokinase infusion.     

A multicenter, randomized, placebo-controlled trial of a new form of intravenous recombinant tissue-type plasminogen activator (activase) in acute myocardial infarction

A new, predominantly single chain preparation of recombinant tissue-type plasminogen activator was evaluated to determine coronary thrombolytic efficacy in 100 patients with acute myocardial infarction. At 3.6 +/- 1.2 hours (mean +/- SD) from symptom onset, patients received either intravenous tissue plasminogen activator (1.25 mg/kg body weight over 3 hours) or placebo on a 3:1 randomized, double-blind basis. Coronary angiography, performed 68 +/- 13 minutes after initiation of the study drug infusion, demonstrated patency of the infarct-related artery in 40 (57%) of 70 patients in the tissue plasminogen activator group compared with 3 (13%) of 23 patients in the placebo group (p less than 0.001). Patients in the placebo group were then eligible to receive intracoronary streptokinase. At 90 minutes the patency was observed in 49 (69%) of 71 tissue plasminogen activator patients compared with 5 (24%) of 21 placebo patients (p less than 0.001). At 120 minutes patency was observed in 59 (79%) of 75 patients of the tissue plasminogen activator group and in 10 (40%) of 25 in the intracoronary streptokinase/placebo group. A nadir value of less than 100 mg/dl fibrinogen occurred in 8 (11%) of 73 patients receiving tissue plasminogen activator versus 8 (40%) of 20 patients treated with intracoronary streptokinase (p = 0.002). Moderate or severe bleeding episodes occurred in 39% of patients treated with tissue plasminogen activator compared with 32% of patients who received placebo/intracoronary streptokinase (p = NS). Thus, this tissue plasminogen activator preparation achieves a high rate of recanalization and, at the doses employed, exhibits increased fibrinogen sparing compared with intracoronary streptokinase.     

Quantitative coronary angiography during intracoronary streptokinase in acute myocardial infarction: How long to continue thrombolytic therapy?

An Intracoronary Infusion of streptokinase is often administered in patients with acute myocardial infarction. To address the question of how long intracoronary streptokinase should be infused, we studied 13 patients with symptoms and electrocardiographic findings suggesting an evolving myocardial infarction. We used subselective catheterization techniques and made quantitative angiographic measurements of the percentage of reduction of coronary artery (CA) diameter before intracoronary streptokinase therapy, immediately after reperfusion was established, and at the completion of streptokinase infusion. Before intracoronary streptokinase and after intracoronary nitroglycerin, nine patients had 100% obstruction of the CA in the “infarct-related vessel.” In seven patients reperfusion was established (25 ± 21 min, mean ± SD) at which time CA diameter was reduced by 77 ± 22%. The streptokinase infusion was then continued until repeated films (every 10 to 15 min) suggested no further change at the site of CA obstruction (93 ± 68 min). The percentage of CA diameter reduction when streptokinase infusion was discontinued was 55 ± 32%; this value was less (P < 0.05) than that observed early after reperfusion. These data show that after initial reperfusion was achieved by the use of intracoronary streptokinase, additional streptokinase lessened the reduction of CA diameter. Residual thrombus may be present at the narrowed CA site early after reperfusion, and further “cleanup” can be achieved by prolonging streptokinase infusion.     

Intracoronary prostaglandin E1 plus streptokinase in acute myocardial infarction

Fourteen patients with acute myocardial infarction (duration of chest pain 5 ± 2 hours) received intracoronary infusion of prostaglandin E₁ (PGE₁) and streptokinase. Intracoronary PGE₁ was followed by intracoronary streptokinase in 10 patients (group A), with successful recanalization in all patients. Of 4 patients in whom recanalization failed with intracoronary streptokinase given first (group B), 2 had successful recanalization after addition of intracoronary PGE₁. Immediately after successful recanalization, left ventricular ejection fraction increased from 50 ± 9% to 62 ± 10% (p < 0.0008), left ventricular end-diastolic pressure decreased from 20 ± 10 to 16 ± 10 mm Hg (p < 0.05) and stroke volume index increased from 34 ± 10 to 44 ± 12 ml/m² (p < 0.02). Infarct segment shortening improved from 9 ± 5 to 18 ± 4% (p < 0.0002). Transient hypotension in 1 patient was the only complication. Follow-up catheterization in recanalized patients at 2 to 10 days showed maintained improvement in left ventricular global and infarct segment function. Reocclusion occurred in 1 patient. Thus, intracoronary infusion of PGE₁ was effective in establishing reperfusion in all patients when followed by streptokinase and was associated with immediately improved left ventricular global and regional function. PGE₁ deserves further evaluation in acute myocardial infarction.     

Blood coagulation shifts in patients with myocardial infarction treated with streptokinase

Variation in major coagulation parameters was assessed in 87 patients with acute myocardial infarction, treated with streptokinase and/or heparin under angiographic control. Streptokinase treatment was associated with a drop in plasma fibrinogen, plasminogen and alpha 2-antiplasmin, and an increase in serum fibrin/fibrinogen degradation products. The magnitude of coagulation shifts was greater in case of intravenous streptokinase infusion (1,000,000 units over 60 min), as compared to intracoronary streptokinase administration in lower doses (120,000-180,000 units over 60-90 min). In all patients with regained coronary flow, fibrinogen, plasminogen and alpha 2-antiplasmin levels began to decline significantly earlier and/or became normal significantly later, as compared to patients with persisting coronary occlusion. The rates and severity of hemorrhagic complications were basically similar in intravenous and intracoronary routes of administration, in spite of different doses and magnitude of coagulation shifts.     

Thrombolytic therapy for acute transmural myocardial infarction. Intracoronary versus intravenous

The application of coronary angiography in coordination with streptokinase administration directly into the occluded coronary artery has served to focus attention on the clinical potential of such therapy. About 75 percent of patients with acute transmural myocardial infarction have been shown to have reperfusion after intracoronary administration of streptokinase. However, the data do not prove that the beneficial effect required regional perfusion. Analysis of biochemical data suggests that the active agent was not confined to the locale of the thrombus, but in fact circulated in significant concentration; furthermore, systemic (intravenous) treatment resulted in reperfusion of a significant proportion (50 percent) of coronary arteries as well. Comparative studies are needed to critically compare angiographic results after regional or systemic therapy and also to assess the impact of reperfusion on possible reduction in long-term morbidity and mortality. Although intracoronary therapy appears to be more effective for inducing reperfusion, intravenous therapy has the potential for greater clinical impact, since it can be instituted more quickly after the onset of symptoms and does not require specialized cardiac catheterization facilities.     

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.     

Effect of prostacyclin on coronary occlusion in acute myocardial infarction

Prostacyclin is a powerful inhibitor of platelet aggregation and induces relaxation of vascular smooth muscle. We have studied the coronary effects of high local concentrations of prostacyclin in 17 patients during the early stages of acute myocardial infarction. We infused graded concentrations of intracoronary prostacyclin and compared the effects to those of intracoronary isosorbide dinitrate before and after an intracoronary infusion of streptokinase. Considerable dilation of the infarct-related stenosis may follow local infusions of prostacyclin in some patients. In general, however, dilation of the infarct-related stenosis or coronary recanalization did not result from infusion of prostacyclin.     

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.     

Combination therapy for evolving myocardial infarction: Intracoronary thrombolysis and percutaneous transluminal angioplasty

Nonsurgical coronary reperfusion for evolving myocardial infarction is a promising new technique for the salvage of jeopardized myocardium. Successful reperfusion can be established by intracoronary infusion of streptokinase in approximately 75 percent of patients within the first 6 hours of transmural infarction [1,2]. Following recanalization, most patients are left with high grade fixed coronary stenoses which are potential sites for recurrent thrombus formation. Since the underlying site for coronary thrombosis is still present, reocclusion may occur. Indeed, early experience suggests that recurrence of thrombosis is not uncommon [3,4]. Therapy for evolving myocardial infarction should, in some patients, involve not only thrombolysis, but also an attack on the fixed coronary lesion. We describe a patient with evolving myocardial infarction who was treated successfully with combination therapy consisting of intracoronary streptokinase followed by percutaneous transluminal coronary angioplasty [5].     

Intracoronary thrombus in syndromes of unstable myocardial ischemia

The association of coronary thrombosis and transmural myocardial infarction is well documented. We have recently observed apparent intracoronary thrombl in patients with unstable myocardial ischemia without transmural infarction. To assess the frequency and angiographic characteristics of intracoronary defects consistent with thrombi, we reviewed the angiograms of all patients undergoing catheterization within 1 month of the onset of unstable angina or the intermediate coronary syndrome. Of 129 such patients, eight (6.2%) had nonoccluding, hazy, or nonopacified intracoronary filling defects consistent with thrombus in angiographically well-opacified vessels. All defects were just distal to a significant (80% to 99%) coronary stenosis. In each instance the thrombus-involved vessel supplied a myocardial segment referable to the electrocardiographically defined area of ischemia. Support for the theory that the intracoronary defects were thrombi includes three patients with enlargement of the filling defects, who underwent repeat angiography within 7 days, and two patients with embolization of defect fragments. Furthermore these defects were angiographically similar to poststenotic intraluminal defects seen transiently in some patients after partial intracoronary streptokinase recanalization. In conclusion, we have observed, angiographically, intracoronary filling defects consistent with thrombus in some patients with unstable myocardial ischemia.     

Intravenous short-term infusion of streptokinase in acute myocardial infarction

Clinically encouraging results can be obtained with an intravenous high dosage, short-term infusion of streptokinase in patients with evolving myocardial infarction. The feasibility and efficacy of the systemic approach of streptokinase therapy is discussed in this report and includes topics such as recanalization success rate, restoration of coronary blood flow, residual coronary artery lesions, salvage of jeopardized myocardium, time limits of effective reperfusion, transluminal angioplasty, coronary bypass surgery, and mortality. The value of high dosage intravenous short-term streptokinase infusion needs to be assessed with properly designed clinical trials.     

Indications for and limitations of coronary thrombolysis

Experimental studies in dogs with coronary thrombi induced by copper wire confirmed the optimal method of intracoronary thrombolysis, and showed that a high-dose, brief intravenous infusion of urokinase can lead to recanalization. The thrombolytic effects of intracoronary thrombolysin at a rate of 50 IU/kg over 10 minutes are similar to the effects of intracoronary urokinase at a rate 500 IU/kg over 20 minutes. Overall reperfusion rates of 83-86% have been achieved. These results indicate that the thrombolytic effect of thrombolysin is 20 times stronger than that of urokinase. The effect of a brief intravenous infusion of urokinase was less than that of intracoronary urokinase. The reperfusion rate in the same experimental model was 40%. Later, a clinical trial of intracoronary urokinase was performed in 47 patients with acute myocardial infarction who were admitted within 12 hours of the onset of symptoms. In 25 of 33 (75.8%) patients with complete occlusion, selective or ostial infusion of urokinase 500 IU/kg over 20 minutes was successful. When given intravenously, recanalization was achieved in 11 of 15 (73%) patients with complete occlusion who were admitted within 6 hours. Both reperfusion rates were similar except for dosage and the duration of infusion.