Effectiveness of intravenous streptokinase on infarct size and left ventricular function in acute myocardial infarction. Prospective and randomized study

Within 3 h after the onset of symptoms of myocardial infarction, 64 patients were randomly assigned to receive either a 1-h intravenous infusion of 1,500,000 IU of streptokinase (SK) or a conventional therapy. Infarct size was estimated in CK gram equivalent (CKg) by measurement of CK-MB every 3 hours during a 48-h period. Enzymatic study revealed that myocardial infarction of the SK group was significantly smaller (61.4 +/- 45 vs. 89.4 +/- 56 CKg, p less than .05). Angiograms were performed at early stage and five weeks after myocardial infarction. At first coronary angiogram, the infarct-related vessel was open in 82% in the SK group versus 12% in controls. The SK group had higher global ejection fraction at second angiogram (57 +/- 11% vs. 49 +/- 11%, p less than .02), but differences in regional wall motion were not significant. By analysis according to patency or occlusion of infarct-related vessel, global and regional ejection fractions were significantly better at first and at second angiograms in all patients and in anterior infarctions with a patent infarct-related coronary artery. There was no significant difference for inferior infarction. We conclude that intravenous streptokinase infusion early after the onset of myocardial infarction reduces infarct size and improves left ventricular function, chiefly in anterior infarction. This benefit appears to be closely correlated to patency of infarct-related vessels.     

Intravenous streptokinase in acute myocardial infarction (I.S.A.M.) trial: serial evaluation of left ventricular function up to 3 years after infarction estimated by radionuclide ventriculography. I.S.A.M. Study Group

The Intravenous Streptokinase in Acute Myocardial Infarction (I.S.A.M.) trial was a prospective, placebo-controlled, double-blind multicenter trial of high-dose short-term intravenous streptokinase in acute myocardial infarction administered within 6 h after the onset of symptoms. Global and regional left ventricular ejection fractions were determined by radionuclide ventriculography in a subset of 120 patients 3 days, 4 weeks, 7 months, 18 months and 3 years after acute myocardial infarction. In patients with anterior myocardial infarction, left ventricular ejection fraction was higher in the streptokinase than in the placebo group 3 days after acute infarction (49 +/- 14% vs. 40 +/- 11%, p = 0.02). This difference of about 10% units in ejection fraction persisted during the 3 year follow-up period. Among streptokinase-treated patients, regional left ventricular ejection fraction was higher within the infarct zone as well as in remote myocardium throughout the follow-up period. Among patients with inferior infarction, no significant differences between the treatment and control groups were demonstrable with respect to global and regional left ventricular ejection fraction. Thus, intravenous administration of streptokinase within 6 h after the onset of symptoms of acute myocardial infarction preserves left ventricular function over a period of greater than or equal to 3 years in patients with acute anterior myocardial infarction. It improves regional myocardial function within the infarct zone as well as in remote areas. In patients with acute inferior myocardial infarction, benefit from intravenous streptokinase is of only minor degree.     

Effects of early high-dose streptokinase intravenously on left ventricular function in acute myocardial infarction

One hundred seven patients who recently had acute myocardial infarction were randomly assigned either to standard heparin therapy or to intravenous streptokinase within 5 hours after the onset of symptoms in 7 hospitals without catheterization facilities. In the third week, the patients were referred to a university hospital, where the patency rate of the infarct-related artery was studied by selective coronary arteriography and left ventricular function by radionuclide angiography. Fifty-five patients received heparin and 52 streptokinase within a mean period of 190 minutes after the onset of symptoms. Seven patients in the heparin group and 4 in the streptokinase group died in hospital. The patency rate of the infarct-related artery was identical in both groups (69% in the heparin group vs 68% in the streptokinase group). Left ventricular ejection fraction was not statistically different (0.44 +/- 0.13 in the heparin group vs 0.45 +/- 0.12 in the streptokinase group). Left ventricular ejection fraction was significantly higher in patients with a patent infarct-related artery than in patients with an obstructed infarct-related artery (0.49 +/- 0.12 vs 0.41 +/- 0.15, p less than 0.01). In patients with inferior wall infarction, left ventricular ejection fraction was identical (0.50 +/- 0.10 in the heparin group vs 0.52 +/- 0.09, in the streptokinase group). In patients with anterior wall infarction, left ventricular ejection fraction was significantly higher in the streptokinase group than in heparin group (0.40 +/- 0.10 vs 0.33 +/- 0.09, p less than 0.05). Analysis of regional wall motion revealed that improvement occurred in the lateral wall of the left ventricle.(ABSTRACT TRUNCATED AT 250 WORDS)     

Beneficial effects of timolol on infarct size and late ventricular tachycardia in patients with acute myocardial infarction

This investigation was undertaken to study the effects of beta-adrenergic blockade with timolol on infarct size and on the incidence of late ventricular tachycardia in patients with acute myocardial infarction of less than 6 hr of evolution. Patients were assigned randomly either to a placebo-treated group (98 patients) or to a timolol-treated group (102 patients). The patients were treated with 5.5 mg iv timolol (or matched placebo) as a bolus divided into four doses during the first 2 hr followed by 10 mg orally twice daily for 1 month. Cumulative total creatine kinase (CK) release, which reflects the amount of myocardial necrosis was 1677 +/- 132 IU/liter in the placebo group (n = 83) and 1274 +/- 73 IU/liter in the timolol group (n = 81, p less than .01), a 24% reduction. Cumulative release of CK-MB was 138 +/- 8 IU/liter in the placebo group and 106 +/- 8 IU/liter in the timolol group (p less than .01), a 23% reduction. Twenty-four hour Holter electrocardiograms were obtained on days 7, 14, 21, and 28 after the onset of the acute myocardial infarction in 80 patients in the placebo group and 82 patients in the timolol group. The incidence of ventricular tachycardia was lower in the timolol than in the placebo group (7 vs 16 patients, p = .05). We conclude that early administration of intravenous timolol followed by oral treatment in patients with acute myocardial infarction reduces infarct size as assessed by CK and CK-MB serum activity, and decreases the occurrence of late ventricular tachycardia.     

Clinical and prognostic significance of lung thallium uptake on rest imaging in acute myocardial infarction

Exercise-induced pulmonary uptake of thallium-201 in patients with ischemic heart disease is probably due to transient pulmonary edema and left ventricular failure induced by exercise. The significance of increased lung uptake of thallium-201 at rest after acute myocardial infarction (AMI) has not been described. Ninety-six patients admitted with chest pain for suspected AMI or unstable angina underwent thallium-201 imaging at rest. Using conventional diagnostic criteria, 62 had AMI, 12 had unstable angina and 22 had neither. Increased lung uptake of thallium-201 was present in 24 of the total 96 (25%) patients, 20 of the 62 (32%) patients with AMI and 4 of 34 (13%) patients with no evidence of infarction. In the AMI group, those with increased lung thallium-201 uptake had a higher mean +/- standard deviation segmental thallium-201 defect score (22 +/- 7 vs 12 +/- 8, p less than 0.0001), lower ejection fraction (35 +/- 14 vs 49 +/- 14%, p less than 0.002), higher peak creatine kinase levels (2,410 +/- 1,247 vs 1,496 +/- 1,228 IU/liter, p less than 0.01), higher wall motion abnormality score (25 +/- 13 vs 13 +/- 12, p less than 0.0001), increased incidence of clinical in-hospital heart failure (15 of 20 vs 7 of 42, p less than 0.0001) and higher short-term mortality (4 of 20 vs 1 of 42, p less than 0.02) compared to those without increased lung thallium-201 uptake.(ABSTRACT TRUNCATED AT 250 WORDS)     

Value of percutaneous transluminal coronary angioplasty after unsuccessful intravenous streptokinase therapy in acute myocardial infarction

The effect of sequential high-dose intravenous streptokinase (SK) (1.5 million units) followed by emergency percutaneous transluminal coronary angioplasty (PTCA) on preserving left ventricular function was assessed prospectively in 34 patients with acute myocardial infarction (AMI). Intravenous SK therapy was initiated 2.6 +/- 1.3 hours (mean +/- standard deviation) after the onset of chest pain. Urgent coronary angiography showed persistent total occlusion in 13 patients, significant diameter stenosis (70 to 99%) in 18 patients and a widely patent artery (less than 50% stenosis) in 3 patients. Emergency PTCA was performed in 29 patients 5.0 +/- 2.1 hours after symptom onset. Successful recanalization was achieved in 33 of the 34 patients (97%) treated with sequential therapy. Repeat contrast ventriculograms recorded 7 to 10 days after intervention in 23 patients showed that the left ventricular ejection fraction increased from 53 +/- 12% to 59 +/- 13% (area-length method, p less than 0.002). Regional wall motion of the infarcted segments improved from -2.7 +/- 1.1 to -1.5 +/- 1.7 SD/chord (centerline method, p less than 0.003). In the subgroup of patients with an occluded artery on initial angiography (group A, n = 10), both global left ventricular ejection fraction (49 +/- 12% vs 59 +/- 12%, p less than 0.002) and regional wall motion (-3.2 +/- 1.0 vs -1.9 +/- 1.7 SD/chord, p less than 0.002) improved significantly. In contrast, no significant improvement was seen in patients with a patent artery on initial angiography (n = 13). Thus, sequential intravenous SK and emergency PTCA is efficacious in achieving coronary reperfusion and in improving both global and regional left ventricular function.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of early metoprolol injection followed by oral dosage on CK-MB release, and myocardial function in suspected acute myocardial infarction. A double-blind controlled study

The effect of metoprolol on indices of infarct size and left ventricular function was compared with that of placebo in a double-blind randomized trial in patients with definite or suspected acute myocardial infarction. Intravenous metoprolol (15 mg) or placebo was given within 24 h of the onset of symptoms, and oral treatment (200 mg daily) was continued for 15 days. Thirty-five patients received metoprolol and 34 patients placebo. The mean (+/- SD) of maximal creatinine phosphokinase (CK)-MB activities was 142 +/- 110 IU/l in the placebo group and 74 +/- 72 IU/l in the metoprolol group (p less than 0.001). The ECG QRS score at discharge from hospital was 5.22 +/- 4.47 and 4.61 +/- 3.06 (NS), respectively. Global left ventricular ejection fraction at rest was 44 +/- 14 and 51 +/- 15% (p = 0.054), respectively, and no change occurred in either group from rest to peak exercise. Ventricular fibrillation occurred in 1 placebo patient during the first day in hospital and in 1 metoprolol patient on the 14th day. Holter monitoring revealed no significant difference in the occurrence of ventricular arrhythmias during the first 24 h. Smaller enzyme release and higher ejection fraction suggest myocardial protection by early metoprolol treatment in acute myocardial infarction.     

Randomized double-blind trial of intravenous streptokinase for acute myocardial infarction

To determine the efficacy of intravenously administered streptokinase (SK) on infarct artery patency, global left ventricular (LV) function and clinical course in transmural acute myocardial infarction (AMI), 38 patients were studied using a randomized, double-blind, placebo-controlled scheme. Nineteen patients received 1.0 million units of SK followed by 72 hours of heparin infusion and 19 received placebo followed by heparin infusion, all within 5 hours (mean 3.3 hours) after AMI onset. Patients ineligible for inclusion in the randomized trial were followed as a second, "historical control" group. Compared with placebo, SK caused a higher frequency of enzymatic evidence of reperfusion (6% vs 79%, p less than 0.001) and of patent infarct-related arteries at predischarge coronary arteriography (64% vs 88%, difference not significant). (Patients in the control group had a relatively low frequency of spontaneous thrombolysis--28%.) In the SK group LV ejection fraction increased from early (average 7.3 hours after AMI) to late (predischarge) study (from 40% early to 47% late, p less than 0.05); in the placebo group LV ejection fraction did not change significantly (from 41% to 42%). Predischarge exercise radionuclide ventriculography showed mild and similar degrees of inducible ischemia in both groups. After a mean of 12.8 months of follow-up, 1 SK patient and 4 placebo patients had died (difference not significant). In conclusion, intravenous SK is efficacious for thrombolysis in patients with AMI. It improves global LV function without augmenting exercise-inducible ischemia.     

Early beneficial effect of streptokinase on left ventricular function in acute myocardial infarction

The effect of intravenous streptokinase therapy on the time course of functional recovery was investigated in a controlled study of 64 patients randomized within 3 hours after the onset of acute myocardial infarction (AMI). Contrast ventriculography was performed 1 to 4 days after AMI and repeated 5 weeks later. Wall motion was analyzed by the centerline method in the central infarct, peripheral infarct and noninfarct regions. In patients with ventriculographic data at the early catheterization, streptokinase-treated patients had less severe hypokinesia in the central infarct region than control patients (-2.9 +/- 0.9 [n = 29] vs -3.4 +/- 0.7 standard deviations below normal [n = 21], p less than 0.05). The benefit of streptokinase was more marked in the peripheral infarct region (-1.5 +/- 0.7 vs -2.1 +/- 0.6, p less than 0.001). As a result, the ejection fraction was slightly higher in treated versus control groups (46 +/- 10 vs 43 +/- 7%, respectively; difference not significant). At 5 weeks, function in the streptokinase and control groups had diverged further because of continued improvement in the streptokinase-treated patients. This study shows that streptokinase benefits left ventricular (LV) function by 1 to 4 days after AMI, earlier than previously reported. The benefit was not limited to the peripheral infarct region, where ischemia might have been less severe, but was also seen in the central infarct region. The implication is that thrombolytic therapy can improve LV function during the period of myocardial stunning, while myocardial function is still recovering.     

Improvement of left ventricular dysfunction during exercise by walking in patients with successful percutaneous coronary intervention for acute myocardial infarction.

A growing body of evidence suggests that walking reduces the incidence of coronary events, so the present study investigated whether walking influences left ventricular function in 30 patients with acute myocardial infarction (AMI) who had undergone successful percutaneous coronary intervention (PCI). The patients were randomly assigned to either a 3-month exercise training program of walking (group W, n=15) or a control group (group C, n=15). At both the beginning and end of the study, patients underwent exercise stress echocardiography to determine left ventricular ejection fraction (LVEF) at rest and during exercise. At baseline, there was no difference in LVEF at rest or during exercise between the two groups. After 3 months, LVEF during exercise was significantly improved compared with at rest in group W (61+/-3% during exercise vs 57+/-5% at rest, p<0.01), whereas no difference was observed between the LVEF at rest and that during exercise in group C (54+/-5% at rest vs 52+/-7% during exercise, NS). Walking may be beneficial for improving left ventricular function during exercise in patients with AMI.     

High dose intravenous streptokinase in acute myocardial infarction

Early recanalization of infarct-related coronary arteries has been attempted in 40 patients with acute myocardial infarction (AMI) and angiographically proven total occlusion by brief high dose intravenous streptokinase infusion (IVSK). In 24 patients (60%) recanalization was achieved after 48 +/- 14 min of IVSK at an infusion rate of 30,000 to 40,000 IU/min (group A), in 16 patients there was a late (greater than 2 h) or no recanalization (group B). The total dose of SK was 1.7 +/- 0.48 Mio IU in group A and 1.74 +/- 0.41 Mio IU in group B, the time from the onset of symptoms to peak myocardial enzyme of creatine phosphokinase (CKMB) 11 +/- 3 h in group A and 22 +/- 6 h in group B (p less than 0.001). Biplane left ventricular ejection fraction increased from 55 +/- 9% at the time of acute angiography to 58 +/- 10% after 14 to 24 days in group A (p less than 0.1) and decreased from 49 +/- 11 to 41 +/- 11% in group B (p less than 0.005). There were four reocclusions in group A, two could be reopened by i.v. urokinase (1 Mio IU over 30 min). During a follow-up period of 18 +/- 8 months one patient in group A died from an early ventricular rupture 2 hours after recanalization, and one patient in group B from heart failure 7 months after IVSK. There was no serious bleeding or other complication related to IVSK. We conclude that IVSK is an effective and safe means of early recanalization of coronary thrombosis in AMI, and feasible in the majority of patients with AMI.     

Limitation of myocardial infarct size and preservation of left ventricular function by early administration of APSAC in myocardial infarction

In cases of acute myocardial infarction (MI), it has been shown that preserving left ventricular function and limiting infarct size with early reperfusion of the occluded artery by means of a thrombolytic agent could eventually result in a reduced mortality rate. The aim of the APSIM study (anisoylated plasminogen streptokinase activator complex [APSAC] dans l'infarctus du Myocarde) was to demonstrate that early administration of APSAC in patients with recent acute MI could limit the infarct size and preserve left ventricular systolic function. In all, 231 patients with a first acute MI were randomly allocated to either APSAC (30 U over 5 minutes) or to conventional heparin therapy (5,000 IU in bolus injection) within 5 hours of the onset of symptoms. Of these patients, 112 received APSAC and 119 received heparin within a mean period of 188 +/- 62 minutes after the onset of symptoms. The patency rate of the infarct-related artery was 77% in the APSAC group and 36% in the heparin group (p less than 0.001). Left ventricular ejection fraction determined from contrast angiography was significantly higher in the APSAC than in the heparin group. This was true for the entire population (0.53 +/- 0.13 vs 0.47 +/- 0.13, p = 0.002) as well as for the subgroups of anterior and inferior wall infarctions (0.47 +/- 0.13 vs 0.4 +/- 0.16, p = 0.004 and 0.56 +/- 0.11 vs 0.51 +/- 0.09, p = 0.02). At 3 weeks, the difference remained significant for patients with anterior MI.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of thrombolytic therapy on exercise response during early recovery from acute myocardial infarction: a placebo controlled study.

Several studies have shown that infarct size is reduced following thrombolytic treatment in patients with acute myocardial infarction. Exercise test variables, such as an impaired heart rate response during exercise, are known to be related to left ventricular function and patient prognosis following acute myocardial infarction. The present study was performed to compare exercise test variables in acute myocardial infarction patients following either intravenous thrombolysis or placebo. Symptom-limited bicycle ergometer tests, carried out 1-2 weeks from the infarction, were performed in 85 patients randomized to intravenous streptokinase (N = 41) or placebo (N = 44) given within 12 h from onset of symptoms. At rest heart rate, systolic blood pressure and rate-pressure product were similar in the two groups. At maximum workload the streptokinase treated patients had a higher median maximal heart rate than controls (136 vs. 126 b.min-1, P less than 0.01) but only a trend towards higher systolic blood pressure was seen (175 vs. 163 mmHg, P = 0.09). Rate-pressure product at maximal exercise was 23,620 vs. 20,100 mmHg.b.min-1 respectively, (P less than 0.01). Total exercise time, ST-segment deviation, occurrence of angina pectoris and left ventricular ejection fraction were similar in the two groups. The trend towards an increased heart rate at maximum workload in streptokinase-treated patients was seen at all levels of left ventricular ejection fraction, and at all levels of exercise capacity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of glucose-insulin-potassium infusion on ST-elevation myocardial infarction in patients treated with thrombolytic therapy

The role of glucose-insulin-potassium (GIK) infusion in the management of acute myocardial infarction is not well established. This prospective, randomized study comprised 120 patients who had ST-elevation myocardial infarction that was treated within 12 hours from symptom onset with a high dose of GIK (25% glucose, 50 IU of soluble insulin per liter, and 80 mmol of potassium chloride per liter at 1 ml/kg/hour over 24 hours) as adjunct to thrombolytic therapy (1.5 MU of streptokinase/30 to 60 minutes; GIK group) or thrombolytic therapy alone (control group). The primary end point of the study was the rate of major adverse cardiac events (MACEs) at 1 month, defined as a composite of cardiac death, reinfarction, serious arrhythmias (ventricular fibrillation and/or tachycardia), and severe heart failure. The secondary end points were the rate of MACEs at 1 year and improvement in left ventricular systolic function. The incidence of MACEs at 1 month was significantly lower in the GIK group (10% vs 32.5%, relative risk 0.24, 95% confidence interval 0.09 to 0.63, p = 0.0043). Patients in the GIK group had significant decreases in ventricular tachycardia and/or fibrillation (1.3% vs 15.0%, p = 0.003) and severe heart failure (3% vs 12.5%, p = 0.031). The rate of MACEs at 1 year was also significantly lower in the GIK group (13% vs 40.0%, relative risk 0.22, 95% confidence interval 0.09 to 0.55, p = 0.0012). After 1 year, there was a significant improvement in left ventricular ejection fraction in the GIK group (from 48 +/- 8% to 51 +/- 10%, p <0.01), which was not observed in the control group. In conclusion, high-dose GIK, used as an adjunct to thrombolytic therapy, was safe and improved clinical outcome at 1 month. The beneficial effect of GIK infusion was maintained up to 1 year.     

Arteriographic predictors of spontaneous improvement in left ventricular function after myocardial infarction

To better characterize the changes in left ventricular ejection fraction after myocardial infarction, we compared radionuclide ventriculograms obtained acutely and 2 weeks after acute myocardial infarction in 40 patients. These patients underwent angiography within a mean of 4 hr and 20 min after the onset of symptoms of infarction and either received no therapy (32 patients who were control subjects in a thrombolysis trial) or did not experience reperfusion (eight patients) despite receiving streptokinase infusions. In all 40 patients, the change in left ventricular ejection fraction over 2 weeks was small (+2.6%). Patients were then grouped according to the presence or absence of residual flow on their angiograms. Residual flow was considered to be present in 21 patients, in 12 by virtue of subtotal occlusion of the artery supplying the area of infarct and in nine because of well-developed coronary collaterals to the distal infarct artery. Mean change in ejection fraction for patients with residual flow was +6.9 +/- 2.3% vs -2.2 +/- 1.7% for patients without residual flow (p less than .01). Fourteen of 21 (67%) patients with residual flow had a spontaneous rise in ejection fraction of greater than 5%, as compared with two of 19 (11%) patients without residual flow (p less than .01). Time to peak level of creatine kinase (CK) was significantly shorter in the residual flow group (15 vs 23 hr, p less than .01), while the peak level of CK was lower (1550 vs 2220 IU) in these patients. This latter difference did not reach statistical significance (p = .10).(ABSTRACT TRUNCATED AT 250 WORDS)     

Intravenous streptokinase in acute myocardial infarction (I.S. A.M.): assessment of left ventricular function 1 and 7 months after infarction by radionuclide ventriculography

l.S.A.M. was a prospective, placebo-controlled, double-blindmulticentre trial of high-dose short-term intravenous streptokinasein acute myocardial infarction (AMI) within 6 h of the onsetof symptoms. Determination of left ventricular ejection fraction(LVEF) by radionuclide ventriculography was performed 1 and7 months after AMI in a subset of 192 patients at rest and,in 140 of them, also during exercise. Regional myocardial functionwas analysed in all 145 patients with neither a history of aprevious myocardial infarction nor revascularization proceduresor reinfarction within the 7-month follow-up period. One month after AMI, mean LVEF was higher in the streptokinasegroup in patients with anterior AMI (50±15% vs 42 ±16%,P = 0.013). This difference was more marked in the subgrouptreated within 3 h (53 ± 14% vs 42 ± 15%, P =0.004), whereas patients treated 3–6 h after the onsetof symptoms did not differ from respective controls (41 ±16%vs 41 ±18%). In patients with inferior A MI, the differencein mean LVEF was small (57±11% vs 55 ±12%, P =0.47). After anterior AMI benefit due to streptokinase therapywas preserved up to 7 months (52 ±14% vs 44 ±17%,P = 0.013). During exercise, the increase of mean LVEF was greaterin the streptokinase group at both dates, especially 7 monthsafter AMI (41 ±61% vs l.2±6.3%, P = 0.015). Instreptokinase-treated patients with anterior AMI, regional LVEFat rest was higher at both dates compared with controls, withinthe infarct zone as well as in remote myocardium. No treatment-controldifferences were demonstrable in patients with inferior AMI.During exercise, regional contractile reserve was better inthe streptokinase group within the infarct zone as well as inremote myocardium, irrespective of the site of infarction. Thus, intravenous streptokinase within 3 h after the onset ofA MI preserves global left ventricular function m anterior AMIover a period of at least 7 months. Intravenous streptokinaseimproves regional myocardial function within the infarct zoneas well as in remote areas. In inferior AMI investigation solelyat rest may underestimate the benefit of streptokinase therapy.     

A randomized controlled trial of intravenous streptokinase in evolving acute myocardial infarction

To determine the efficacy of intravenous streptokinase in acute myocardial infarction, 52 patients were randomized to intravenous streptokinase or control groups. Time from onset of infarction to randomization was similar in the streptokinase group and control group, 4.9 +/- 2.1 hours vs 5.4 +/- 2.4 hours, respectively. The 28 streptokinase patients received an intravenous infusion of 700,000 units of streptokinase followed by full-dose anticoagulation. The 24 control patients received normal saline solution followed by full-dose anticoagulation. Of 28 streptokinase patients, 12 (43%) had noninvasive evidence of reperfusion by early peaking of serum creatine kinase (peak creatine kinase less than 16 hours after onset of infarction) vs 3 of 24 control patients (13%), p less than 0.02. Two streptokinase patients (7%) had reperfusion arrhythmias during streptokinase infusion. One streptokinase patient (4%) and two control patients (8%) died during hospitalization. At angiography (16 +/- 5 days after infarction) 22 of 26 streptokinase patients (85%) had a patent infarct-related coronary artery compared to 8 of 20 control patients (40%), p less than 0.01. Comparison of radionuclide left ventricular ejection fraction assessed acutely (28 +/- 10 hours after infarction) with left ventricular ejection fraction at hospital discharge (15 +/- 3 days after infarction) showed no significant improvement in either the streptokinase or control group, 0% and +1%, respectively. At follow-up 13 +/- 7 months after infarction, total mortality rate was similar in the streptokinase group and control group, 17.8% (5 of 28 streptokinase patients) and 20.8% (5 of 24 control patients), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Rescue thrombolysis: alteplase as adjuvant treatment after streptokinase in acute myocardial infarction.

BACKGROUND--In acute myocardial infarction patients who do not reperfuse their infarct arteries shortly after thrombolytic treatment have a high morbidity and mortality. Management of this high risk group remains problematic, especially in centres without access to interventional cardiology. Additional thrombolytic treatment may result in reperfusion and improved left ventricular function. METHODS--Failure of reperfusion was assessed non-invasively as less than 25% reduction of ST elevation in the electrocardiographic lead with maximum ST shift on a pretreatment electrocardiogram. 37 patients with acute myocardial infarction who showed electrocardiographic evidence of failed reperfusion 30 minutes after 1.5 MU streptokinase over 60 minutes were randomly allocated to receive either alteplase (tissue type plasminogen activator (rt-PA) 100 mg over three hours) (19 patients) or placebo (18 patients). 43 patients with electrocardiographic evidence of reperfusion after streptokinase acted as controls. Outcome was assessed from the Selvester Q wave score of a predischarge electrocardiogram and a nuclear gated scan for left ventricular ejection fraction 4-6 weeks after discharge. RESULTS--Among patients in whom ST segment elevation was not reduced after streptokinase, alteplase treatment resulted in a significantly smaller electrocardiographic infarct size (14% (8%) v 20% (9%), P = 0.03) and improved left ventricular ejection fraction (44 (10%) v 34% (16%), P = 0.04) compared with placebo. This benefit was confined to patients who failed fibrinogenolysis after streptokinase (fibrinogen > 1 g/l). In patients in whom ST segment elevation was reduced after streptokinase, infarct size and left ventricular ejection fraction were not significantly different from those in patients treated with additional alteplase. CONCLUSION--Patients without electrocardiographic evidence of reperfusion after streptokinase may benefit from further thrombolysis with alteplase.     

Intravenous streptokinase during acute myocardial infarction. A prospective open study

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

Diabetes mellitus prevents ischemic preconditioning in patients with a first acute anterior wall myocardial infarction

OBJECTIVES: This study was undertaken to assess whether prodromal angina could have beneficial effects in diabetic patients with acute myocardial infarction (AMI). BACKGROUND: Prodromal angina occurring shortly before the onset of AMI is associated with favorable outcomes by the mechanism of ischemic preconditioning. However, little is known about the impact of diabetes on ischemic preconditioning. METHODS: We studied 611 patients with a first anterior wall AMI who underwent emergency catheterization within 12 h after the onset of chest pain: 490 patients without diabetes and 121 patients with non-insulin treated diabetes. Prodromal angina was defined as angina episode(s) occurring within 24 h before the onset of AMI. Serial contrast left ventriculograms were obtained in 424 patients at the time of acute and predischarge catheterization. RESULTS: In non-diabetic patients, prodromal angina was associated with lower peak creatine kinase (CK) value (3,068 +/- 2,647 IU/l vs. 3,601 +/- 2,462 IU/l, p = 0.037), larger increase in left ventricular ejection fraction (LVEF) (10.1 +/- 13.0% vs. 5.8 +/- 13.4%, p = 0.004) and lower in-hospital mortality (3.4% vs. 9.3%, p = 0.015). On the contrary, in diabetic patients, there was no significant difference in peak CK value (3,382 +/- 2,520 IU/l vs. 3,233 +/- 2,412 IU/l, p = NS), the change in LVEF (6.7 +/- 13.8% vs. 7.1 +/- 12.4%, p = NS) and in-hospital mortality (8.8% vs. 11.0%, p = NS) between patients with and patients without prodromal angina. CONCLUSIONS: Prodromal angina limited infarct size, enhanced recovery of LV function and improved survival in non-diabetic patients with AMI. However, such beneficial effects of prodromal angina were not observed in diabetic patients, suggesting that diabetes might prevent ischemic preconditioning.