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.     

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].     

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.     

Intracoronary infusion of streptokinase in patients with acute myocardial infarction: Effects of reperfusion on left ventricular performance

Cardiac catheterization and coronary angiography were performed on hospital admission in 32 consecutive patients with acute myocardial infarction. Twenty-six patients had total occlusion of an infarct-related coronary artery and six had severe proximal stenosis with poor distal flow. In 18 of the 26 patients with total occlusion, intracoronary infusion of Streptokinase resulted in reperfusion of the distal coronary artery. Seventeen of these 18 patients had severe coronary arterial stenosis at the site of the previous total occlusion. Hemodynamic indexes of left ventricular performance and ejection fraction determined by gated cardiac blood pool imaging did not change immediately after reperfusion (p [probability]= not significant [NS]). The mean (± standard deviation) left ventricular ejection fraction increased significantly (p = 0.007) from admission (44 ± 15 percent) to hospital discharge (55 ± 7 percent) in patients evidencing reperfusion of the occluded coronary artery. It did not change (p = NS) in this time span in the patients with severe stenosis alone, in those with total occlusion not demonstrating reperfusion after administration of streptokinase or in an additional 10 control patients with acute myocardial infarction not evaluated with coronary angiography. These data suggest that (1) coronary arterial thrombus is frequent in acute myocardial infarction and can be lysed by intracoronary streptokinase; (2) reperfusion with intracoronary streptokinase in acute myocardial infarction results in improved left ventricular performance between admission and hospital discharge.     

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.     

Percutaneous transluminal coronary angioplasty in acute myocardial infarction

Percutaneous transluminal coronary angioplasty (PTCA) has, in general, been restricted to therapy for patients with angina pectoris. Thrombolytic therapy and guide wire recanalization have been used to recanalize coronary arteries in patients with evolving myocardial infarction. Recently we and others have examined the use of PTCA to recanalize the acutely occluded artery associated with the early evolving phase of myocardial infarction. PTCA was performed as definitive therapy in eight patients with acute myocardial infarction. Seven of these had totally occluded arteries to the region of infarct. The infarct-related artery was open within 20 minutes in each of these cases. PTCA recanalization resulted in evidence for reperfusion in each case. Residual stenoses either were not present or were minimal. The procedure was well tolerated. These preliminary results suggest that PTCA may be a reasonable alternative to intracoronary thrombolytic therapy in certain patients with acute evolving myocardial infarction.     

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.     

Acute myocardial infarction: intracoronary application of nitroglycerin and streptokinase.

In five patients with acute myocardial infarction, the effects of both intracoronary nitroglycerin (NTG) and subsequent intracoronary streptokinase application were evaluated. In addition, transluminal recanalization was performed in one of these patients. Injection of NTG into the infarct-related coronary artery resulted in improved distal filling of the subtotally occluded left circumflex artery in one patient, and in transient patency of the completely occluded right coronary artery in a second patient. In a third patient patency of the totally occluded left anterior descending artery (LAD) was achieved by transluminal recanalization with a guide wire. In a forth patient with occulsion of the LAD, there was no response to intracoronary NTG and mechanical recanalization was not attempted. Subsequent intracoronary infusion of streptokinase (1,000--2,000 U/min for 15--60 min) resulted in a further and long-term reduction of narrowing at the site of acute occlusion in patients I-III and in opening of the completely occluded LAD in patient IV. Improvement of lumen was paralleled by alleviation of symptoms. In a fifth patient, in whom the LAD was subtotally occluded, the degree of coronary obstruction could not be changed by intracoronary application of NTG or by lysis. In this patient, symptoms and ECG changes improved with reduction of pathologically elevated blood pressure values. The findings suggest that myocardial infarction had been caused by thrombotic occulsion in four patients, and that spasm of the infarct vessel could have been an additional factor in two of these patients. In the fifth patient, an increase of afterload in the presence of a subtotal lesion might have caused the critical imbalance between oxgen supply and demand, resulting in cell death.     

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.     

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.     

Evaluation of the effectiveness of intracoronary streptokinase infusion in acute myocardial infarction: Postprocedure management and hospital course in 204 patients

A multicenter study evaluated the early management and subsequent hospital course of 204 patients with acute myocardial infarction who were receiving intracoronary infusions of streptokinase (STK). The in-hospital mortality in 37 patients with thrombotic occlusion of the infarct-related vessel, in whom recanalization could not be achieved, was 24%. However, the cardiac mortality in 129 patients who were successfully treated by percutaneous transluminal coronary recanalization (PTCR) was only 5.4%. Cardiac deaths (five patients) and nonfatal reinfarctions (20 patients) occurred in the early period in the cardiac care unit (CCU) in 21% of the latter group and, despite anticoagulation measures, could not be consistently prevented. Hemorrhagic complications, necessitating blood transfusion, occurred in 15 (7.4%) of the total 204 patients in the group, usually in the acute CCU stage, and were positively related to decline of fibrinogen serum concentrations below 100 mg/dl and to use of the Judkins technique. The later course of most of the patients on the general ward was uneventful until hospital discharge. Thus there were only two more cardiac deaths, and of 64 successfully treated STK-PTCR patients who left the CCU without clinical indications of reinfarction and agreed to repeat coronary angiography before hospital discharge, the infarct-related vessel was patent in 59 patients and reoccluded in only five (7.8%).     

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.     

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.     

Coronary thrombolysis with recombinant human tissue-type plasminogen activator: a prospective, randomized, placebo-controlled trial

Forty-five patients with acute transmural myocardial infarction and angiographically confirmed complete coronary occlusion were prospectively randomized, two for one, to treatment of acute coronary thrombosis with intravenous recombinant human tissue-type plasminogen activator (rt-PA) or placebo. Each of five additional consecutive patients was treated with a high dose of rt-PA for 2 hr. Twenty-five of 33 patients (75%) receiving 0.5 to 0.75 mg/kg of rt-PA over 30 to 120 min had angiographically proven recanalization within 90 min of initiation of therapy. Only one of 14 patients given placebo had spontaneous recanalization within 45 min (p less than .001). Thirteen placebo-treated patients were crossed over to the intracoronary rt-PA group. Nine (69%) exhibited subsequent recanalization within 45 min. Levels of circulating fibrinogen decreased after treatment with rt-PA by an average of only 8% of baseline values. None of the patients manifested a depletion of fibrinogen level to below 100 mg/dl. Six patients who were completely unresponsive to rt-PA were subsequently treated with intracoronary streptokinase and none responded. Thus, either intravenous or intracoronary rt-PA induced coronary thrombolysis without eliciting clinically significant fibrinogenolysis in patients with evolving myocardial infarction due to thrombotic coronary occlusion.     

Influence of reperfusion on serum concentrations of cytosolic creatine kinase and structural myosin light chains in acute myocardial infarction

The kinetics of cytosolic and structural marker protein release from myocardium were studied in 44 patients with acute myocardial infarction. After intracoronary infusion of streptokinase, there was early recanalization of the infarct-related artery in 8 patients and late recanalization in 18. In 18 patients the infarct-related artery remained occluded. Creatine kinase (CK) level peaked and normalized significantly earlier in patients with early reperfusion than in patients with late reperfusion, and in patients with late reperfusion earlier than in patients with permanent occlusion. Thus, the interval of absolute diagnostic sensitivity of CK depends on early infarct perfusion. In contrast, release of myosin light chains was not significantly changed by recanalization of the infarct-related artery compared with that in nonreperfused myocardial infarction. Thus, in patients with acute myocardial infarction, myosin light chains may be superior to CK as a diagnostic means and for estimation of infarct size.     

Myocardial reperfusion by thrombolysis after acute total left main artery occlusion--a case report

Coronary recanalization with thrombolytic agents is a new therapeutic approach to the treatment of acute myocardial infarction that can be beneficial even to patients in cardiogenic shock. Although few cases have been reported in the literature, treatment of acute occlusion of the left main coronary artery (LMCA) has been made possible by myocardial reperfusion. This communication concerns a patient with acute LMCA occlusion who was successfully treated by thrombolytic therapy with streptokinase followed by revascularization of the myocardium seventy-two hours after reperfusion was achieved.     

Coronary artery spasm immediately after percutaneous transluminal coronary recanalization

A 55-year-old man developed acute inferior myocardial infarction. A coronary arteriogram performed within two hours later showed complete occlusion of the right coronary artery, which was not resolved by two doses of 300 micrograms of intracoronary nitroglycerin. It was recanalized with 50% luminal diameter narrowing after 600,000 units of urokinase. Immediately after this thrombolytic therapy, the patient experienced chest pain, and the coronary artery became completely obstructed again. The pain was promptly relieved by 300 micrograms of intracoronary nitroglycerin, with disappearance of the obstruction. The observations during the procedure indicate that coronary artery spasm can occur after successful thrombolytic therapy on an occluded artery, inducing postinfarction angina, and might culminate in a second complete occlusion after percutaneous transluminal coronary recanalization.     

Intracoronary thrombolysis 3 to 13 days after acute myocardial infarction for postinfarction angina pectoris

The restoration of anterograde coronary flow long after coronary thrombosis may be of benefit to patients with continuing ischemia. To determine whether “old” intracoronary thrombi are susceptible to lysis with thrombolytic agents, 18 patients with angina at rest during evolving acute myocardial infarction (AMI) and total occlusion of the infarct vessel were treated with Intracoronary streptokinase 3 to 13 days after onset of AMI. In 12 of the 18 patients (67%), successful recanalization of the artery was achieved 6.9 ± 2.7 days after AMI. Thrombolysis was followed by coronary angioplasty in 2 patients. To evaluate the efficacy of this approach in reducing post-AMI Ischemia, the number of episodes of angina at rest was compared in patients with successful and unsuccessful attempts at recanalization. Even in patients without angioplasty, the mean number of daily episodes decreased from 1.02 ± 0.6 to 0.09 ± 0.2 in patients In whom reperfusion was achieved, and from 1.07 ± 0.8 to 0.88 ± 0.8 in those in whom it was not (p = 0.027 for the difference between the groups). Thus, in patients with early post-AMI angina, intracoronary streptokinase can restore flow in the occluded artery, may decrease the frequency of angina, and allows angioplasty to be performed.     

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.     

Necropsy evaluation in seven patients with evolving acute myocardial infarction treated with thrombolytic therapy

Systemic and intracoronary streptokinase application may recanalize a coronary artery occluded by a thrombus in patients with acute myocardial infarction (MI). However, thrombolysis fails in a number of patients for unknown reasons. The coronary and myocardial histologic characteristics were studied in 3 patients in whom recanalization was successful without subsequent reocclusion, and in 4 patients in whom recanalization was unsuccessful. All patients died within 4 weeks after the acute intervention. Serial sections from the angiographically localized occlusive site of the infarct vessel, and transverse slices of the heart stained with nitroblue tetrazolium for delineation of MI, were examined by light microscopy. Successfully recanalized arteries were patent at necropsy and showed obstructive fibrous atherosclerotic plaques. Among patients in whom recanalization was unsuccessful, 1 patient had occlusions from nonatherosclerotic intramural hemorrhage and 1 from persisting long, mixed old and fresh thrombus, and 2 patients had high-grade obstructions from ruptured atherosclerotic plaques with intimal hemorrhage and residual clot. Reperfused infarct tissue consisted predominantly of contraction band necroses, whereas MIs without reperfusion showed coagulation necroses of the muscle fibers. The results suggest that the success of recanalization depends, in part, on the morphologic features of the coronary occlusion, and that reperfusion after successful thrombolysis may lead to a different pattern of muscle fiber necrosis in the irreversibly injured infarct areas.