Long-term survival in 618 patients from the Western Washington Streptokinase in Myocardial Infarction trials.

OBJECTIVES. The aim of this study was to determine whether streptokinase treatment improves long-term survival in patients with acute myocardial infarction. BACKGROUND. Thrombolytic treatment for acute myocardial infarction reduces early mortality and improves the 1-year survival rate, but the long-term (3 to 8 years) survival benefits of treatment and the relation between survival and baseline clinical characteristics, infarct size and ventricular function have not been established. METHODS. We assessed survival status at a minimum of 3 and a mean of 4.9 +/- 2.3 years in 618 patients randomized between 1981 and 1986 to receive conventional treatment (n = 293) or thrombolysis with streptokinase (n = 325) in the Western Washington Intracoronary (n = 250) and Intravenous (n = 368) Streptokinase in Myocardial Infarction trials. The relation between long-term survival and thrombolytic treatment, admission baseline clinical characteristics and late radionuclide tomographic thallium-201 infarct size and ejection fraction was assessed in a subset of patients. RESULTS. Survival at 6 weeks was 94% in patients who received streptokinase versus 88% in the control group (p = 0.01). However, survival at 3 years was 84% in the streptokinase group and 82% in the control group and for the total period of follow-up, there was no significant survival benefit (p = 0.16). Analysis by infarct location showed a higher survival rate at 3 years for patients treated with anterior infarction (76% vs. 67% for the control group), but no overall survival benefit (p = 0.14). Survival at 3 years for patients with an inferior infarction was 89% in the streptokinase group and 91% in the control group (p = 0.62). By stepwise Cox regression analysis, admission clinical variables associated with decreased long-term survival were anterior infarction, advanced age, history of prior infarction and the presence of pulmonary edema or hypotension. Although streptokinase therapy was associated with improved survival, it was not an independent determinant of survival (p = 0.069). Ejection fraction and thallium-201 infarct size measured approximately 8 weeks after enrollment had a strong association with long-term survival. Univariate analysis in a subgroup of 289 patients with complete data selected infarct size, ejection fraction, age and history of prior infarction as predictors of survival. In the multivariate model, only ejection fraction (p < 0.0001), age (p = 0.008) and prior myocardial infarction (p = 0.02) remained strong predictors. CONCLUSIONS: In these early trials of thrombolytic therapy for acute myocardial infarction, streptokinase improved early survival, but there was little long-term survival benefit. This failure to show an improvement in the 3- to 8-year survival rate may also reflect the need to study a larger group of patients or to initiate treatment earlier after symptom onset.     

Effect of intravenous streptokinase on the relation between initial ST-predicted size and final QRS-estimated size of acute myocardial infarcts

Thrombolytic therapy has been documented to reduce acute myocardial infarct size. The previously established relation between initial ST segment elevation and final electrocardiographic (ECG) myocardial infarct size in patients without coronary reperfusion might therefore be altered by thrombolytic therapy. The effect of intravenous streptokinase on this relation was therefore studied in 73 patients with initial acute myocardial infarction who had participated in the Second International Study of Infarct Survival (ISIS-2). Patients who received streptokinase were considered as one group and patients who did not receive streptokinase as a control group. Final myocardial infarct size, which was estimated from the QRS score, was predicted from the admission standard ECG by previously developed formulas based on ST segment elevation. In the 40 control patients there was no change from ST-predicted to final QRS-estimated infarct size (median 17.7% versus 18.3%; p = NS). In the 33 patients in the streptokinase group, there was a highly significant decrease from predicted to final myocardial infarct size (median 21.9% versus 16.2%; p less than 0.0002). This decrease was found for both anterior (median 23.7% versus 19.5%; p less than 0.03) and inferior (median 21.9% versus 12.0%; p = 0.001) infarct locations. Multiple regression analysis adjusting for differences in predicted infarct size confirmed the significance of streptokinase on the difference in infarct size (p = 0.006). Based on the variability of the percent change from predicted to final infarct size in the control group, a threshold decrease greater than or equal to 20% is required for identification of salvage.(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.     

Influence of coronary collateral vessels on myocardial infarct size in humans. Results of phase I thrombolysis in myocardial infarction (TIMI) trial. The TIMI Investigators

BACKGROUND. The influence of coronary collateral vessels on infarct size in humans remains controversial, partly because no previous study has examined the impact of collaterals present at the onset of acute myocardial infarction on infarct size. METHODS AND RESULTS. The present study used the data base of the Thrombolysis in Myocardial Infarction (TIMI) Phase I trial to correlate the presence or absence of angiographically documented collaterals in the initial hours of myocardial infarct evolution with the size of the infarct as assessed by serial measurements of serum creatine kinase (CK). To avoid the confounding effects of reperfusion on enzymatic estimates of infarct size, this report is limited to those 125 patients who failed to recanalize at 90 minutes after administration of tissue plasminogen activator or streptokinase. Patients with angiographically documented collaterals (group A, n = 51) had significantly lower values of peak serum CK than patients without collaterals (group B, n = 74) (1,877 +/- 216 versus 2,661 +/- 212 IU/l, respectively [mean +/- SEM], p = 0.004). Similarly, CK-derived infarct size estimates were significantly lower in group A than in group B (20.6 +/- 2.5 versus 31.4 +/- 2.8 CK gram equivalents, p = 0.001). The infarct size observed in patients with collaterals was less for anterior infarctions as well as for infarctions of other locations; thus, the beneficial effects of collaterals were independent of the site of the infarct. In 65 of the 125 patients who failed to reperfuse, left ventricular ejection fraction (LVEF) was assessed by contrast ventriculography both at initial cardiac catheterization (before thrombolytic therapy) and at hospital discharge. Among the patients who had both studies, global LVEF tended to increase from pretreatment to hospital discharge in group A (from 50.6 +/- 1.8% to 53.4 +/- 1.8%, p = 0.10) but decreased in group B patients (from 50.3 +/- 1.8% to 47.8 +/- 1.7%, p = 0.02). At hospital discharge, global LVEF was greater in patients with coronary collaterals (53.5 +/- 1.7% versus 49.6 +/- 1.7%, p = 0.01). CONCLUSIONS. The results demonstrate that, in patients in whom thrombolytic therapy fails to induce reperfusion, the presence of coronary collateral vessels at the onset of myocardial infarction is associated with limitation of infarct size as assessed enzymatically and with improved ventricular function on discharge as assessed by LVEF.     

Effect of streptokinase on left ventricular modeling and function after myocardial infarction: the GISSI (Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico) Trial

It has been shown that streptokinase administration at the time of acute myocardial infarction reduces mortality significantly, and that this reduction in mortality should be related to salvage of jeopardized myocardium and preservation of left ventricular function. To better define the relation between thrombolytic therapy and left ventricular modeling and function after acute myocardial infarction, 331 consecutive patients enrolled in the Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico trial were studied by two-dimensional echocardiography just before discharge from the hospital. A 6 month follow-up examination was also available in 232 of these patients. Ventricular volumes were computed from an apical four chamber view, according to a previously published algorithm. An infarct size index was also semiquantitatively assessed, according to the number of akinetic and dyskinetic segments in an 11 segment left ventricular model. At predischarge examination, the 161 patients assigned to streptokinase treatment showed smaller ventricular volumes (end-diastolic volume 119.3 +/- 49.7 versus 134.5 +/- 57.8 ml [p = 0.011]; end-systolic volume 65.4 +/- 36.4 versus 74.9 +/- 45.7 ml [p = 0.036]) and smaller regional wall motion index (2.2 +/- 1.9 versus 2.7 +/- 1.9 segments; p = 0.019) compared with values in the 170 patients assigned to standard care; there was no difference in ejection fraction (46.6 +/- 14.1 versus 45.9 +/- 14.9%; p = 0.64). For both groups of patients, there was a significant relation between end-systolic volume and regional wall motion index (p less than 0.001); for large and similar extents of infarct size, ventricular volume was smaller in patients assigned to thrombolytic treatment than in patients assigned to standard care. At 6 months' follow-up, the differences in volume and regional dysfunction detected at the early examination persisted: 110.8 +/- 47.6 versus 127.9 +/- 53.8 ml for end-diastolic volume (p = 0.001), 56.3 +/- 33.6 versus 69.4 +/- 42.1 ml for end-systolic volume (p = 0.001) and 1.8 +/- 1.8 versus 2.3 +/- 1.8 segments for regional wall motion index (p = 0.001). Again, for comparable extents of infarct size, end-systolic volume was smaller in patients who received streptokinase (n = 110) than in those assigned to conventional treatment (n = 122). It is concluded that streptokinase improves left ventricular modeling and function in patients with myocardial infarction, reducing the extent of regional wall motion abnormalities and lessening postinfarction ventricular dilation. The beneficial effects persist up to 6 months.     

Thrombolytic therapy for acute coronary obstruction: status in 1986

The effect of thrombolysis in acute myocardial infarction on enzymatic infarct size, left ventricular function, and early mortality was studied in subsets of patients in a randomized trial at The Netherlands Interuniversity Cardiological Institute during a 5-year period. Early thrombolytic therapy with intracoronary streptokinase (152 patients) or with intracoronary streptokinase preceded by intravenous streptokinase (117 patients) was compared to conventional treatment (264 patients). All 533 patients were admitted to the coronary care unit within 4 hours after onset of symptoms indicative of acute myocardial infarction. There were 488 patients eligible for this detailed analysis, of whom 245 were allocated for thrombolytic therapy. Early angiography was performed in 212 of the 245 patients. Patency of the infarct-related artery was achieved in 181 patients (85%). Enzymatic infarct size measured from cumulative alpha HBDH release was smaller in patients allocated to thrombolytic therapy (median 760 U/l vs. 1179 U/l in controls, p = 0.0001). LVEF measured by radionuclide angiography before discharge was higher after thrombolytic therapy (median 50% vs. 43% in controls, p = 0.0001). The 12-month mortality was lower in patients allocated to thrombolytic therapy (8% vs. 16% in the control group, p < 0.01). In multivariate regression analysis, infarct size limitation, improvement of LVEF, and a 3-month mortality were predicted by ST, time from onset of symptoms to admission, and Killip class at admission. Thrombolysis was most useful in patients admitted within 2 hours after onset of symptoms and in patients with ST of 1.2 mV or more. On the other hand, no beneficial effects of streptokinase on enzymatic infarct size, left ventricular function, or mortality were observed in the subset of patients with ST less than 1.2 mV admitted 2 to 4 hours after onset of symptoms. In the long term, improved survival and enhanced quality of life are most evident after thrombolytic therapy in patients with larger anterior wall infarction, and less pronounced in patients with smaller inferior wall infarction.     

国产重组链激酶急性心肌梗塞溶栓治疗临床试验

观察国产重组链激酶（ｒ－ＳＫ）在急性心肌梗塞（ＡＭＩ）静脉溶栓治疗中的临床疗效和不良反应，对其安全性和疗效作出评价。试验分为随机单盲对照试验组，即ｒ－ＳＫ（上海医科大学研制）５１例，链激酶（ＳＫ，德国赫斯特药厂产品）５１例和ｒ－ＳＫ开放组７１例。所有病例均符合入选和不入选标准，予ｒ－ＳＫ或ＳＫ各１５０万Ｕ于６０分钟静脉注入，观察血管再通的临床指标，过敏反应及出血并发症等。在随机单盲对照试验组中，５１例ｒ－ＳＫ的血管再通率（８０．４％）与ＳＫ（７４．５％）相近。总的１２２例ｒ－ＳＫ患者的血管再通率为７７．１％。ｒ－ＳＫ的不良反应中，寒颤发生率为４．１％，低血压为５．７％，出血发生率为１６．４％，均表现为皮肤，胃肠道或泌尿道的轻微出血，一般不需处理自行消失。由于ｒ－ＳＫ静脉溶栓治疗血管再通率高，过敏反应及低血压的发生率低，程度轻，出血并发症少，认为国产ｒ－ＳＫ为一安全有效的溶栓剂。     

Infarct size limitation: Acute N-acetylcysteine defense (ISLAND trial): Preliminary analysis and report after the first 30 patients

Our previous experimental research and initial clinical observations regarding the use of N-acetylcysteine in the treatment of ischemic and reperfusion injury in acute myocardial infarction gave rise to a study entitled the Infarct Size Limitation: Acute N-acetylcysteine Defense (ISLAND) trial. Today, this randomized, echocardiographically and angio-graphically controlled study includes the first 30 patients with a first anterior wall myocardial infarction: Group A (n = 10) consisting of patients with successful recanalization of the in-farct-related left anterior descending artery by streptokinase without any further treatment, Group B (n = 10) consisting of patients with failed infarct-related artery recanalization, and Group C (n = 10) comprising patients who had successful streptokinase-induced recanalization of the left anterior descending artery plus N-acetylcysteine administration at a dose of 100 mg/kg body weight. The parameters monitored in our study include changes in global and regional left ventricular ejection fraction of the infarct-related segment using echocar-diography and, using electrocardiograms and the Wagner QRS scoring system, the amounts of acutely jeopardized and finally infarcted myocardium. In Group A, global left ventricular ejection fraction rose nonsignificantly within 2 weeks from 37.5 ± 9.6% to 38.5 ± 13.8%; it declined significantly in Group B from 36.2 ± 6.1% to 30.1 ±6.7% (p < 0.05), while it considerably improved in Group C from 41.7 ± 4.1 % to 59.6 ±8.1 % (p < 0.001). Regional left ventricular ejection fraction changed significantly only in Group C: from — 4.5 ± 27.3 to 45.6 ± 16.3 (p < 0.001). In Group A, in which the amount of acutely jeopardized myocardium was 21.7 ± 7.2, infarction actually occurred in 20.4 ± 9.7% (practically no myocardial salvage). In Group B, risk area was 18.1 ± 4.3%, but infarct size rose to a resulting 29.1 ±6.0%. Significant myocardial salvage was accomplished only in Group C: of 26.2 ±8.1% of jeopardized myocardium, infarct size was reduced to 10.8 ± 7.1% (salvage by 58.8%). Also, basic division of patients by therapy showed that, although those with nonidentical findings on their coronary arteries were included into the same groups, patients treated with streptokinase plus N-acetylcysteine had significantly more favorable values of the monitored parameters than those treated with streptokinase alone. We conclude our interim analysis suggests that N-acetylcysteine has a beneficial effect, reducing the functional and structural impacts of myocardial infarction.     

Aspiration thrombectomy during primary percutaneous coronary intervention as adjunctive therapy to early (in-ambulance) abciximab administration in patients with acute ST elevation myocardial infarction: an analysis from Leiden MISSION! acute myocardial infarction treatment optimization program

Background: The benefits of early abciximab administration and thrombus aspiration in ST elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI) have previously been elaborated. However, whether there is an adjunctive effect of thrombus aspiration among STEMI patients, with angiographic evidence of thrombus, receiving early prehospital abciximab remains unclear. Methods: In the context of a fixed protocol for PPCI, 158 consecutive patients with STEMI were enrolled, in whom abciximab was started early before hospital arrival (in‐ambulance); 79 patients who had PPCI with thrombus aspiration (thrombectomy‐facilitated PCI group), were compared to 79 who had PPCI without thrombus aspiration (conventional PCI group) in a prospective nonrandomized study. The primary end‐point was complete ST‐segment resolution within 90 minutes. Secondary end points included distal embolization, enzymatic infarct size as well as left ventricular ejection fraction (LVEF) assessed by gated single‐photon emission computed tomography. Major adverse cardiac events (MACEs) were evaluated up to 12 months. Results: Both groups were comparable for baseline characteristics. ST‐segment resolution was significantly higher in the thrombectomy‐facilitated group (P = 0.002), and multivariate analysis identified thrombectomy as an independent predictor of ST‐segment resolution (OR = 9.4, 95% CI = 2.6–33.5, P = 0.001). Distal embolization was higher in the conventional PCI group among patients with higher thrombus grades. No difference was observed between both groups in infarct size assessed by peak creatine kinase (p = 0.689) and peak Tn‐T levels (P = 0.435). Also, the LVEF at 3 months was similar (P = 0.957). At 12 month clinical follow‐up, thrombus aspiration was, however, associated with reduced all‐cause mortality (log‐rank p = 0.032). Conclusion: Among STEMI patients treated with PPCI and in‐ambulance abciximab, it appears that a selective strategy of thrombus aspiration still has additive benefit. (J Interven Cardiol 2012;25:1–9)     

Mortality and morbidity in suspected acute myocardial infarction in relation to ambulance transport

In 681 patients admitted to the coronary care unit (CCU) atSahlgrenska hospital between 1 May 1983 and 31 May 1984, dueto suspected acute myocardial infarction (MI), the hospitalmortality and morbidity were related to whether the patientswere transferred to hospital by ambulance or not. In the ambulancegroup acute MI developed in 48% (during the first 3 days inhospital) compared with 41% in the non-ambulance group (P= 0.10).The overall mortality rate was 10.4% in the ambulance groupversus 3.8% in the non-ambulance group (P= 0.001). Correspondingfigures for MIpatients were 193% versus 9.1% (P=0.02) In all, patients referred by ambulance had larger infarcts accordingto maximum serum enzyme activity and a higher incidence of congestiveheart failure. Similar findings were observed when MI patientswere analysed separately. On the other hand, the incidence ofventricular fibrillation, requirement for lidocaine, and thecourse of pain was fairly similar in the two groups. In a multivariateanalysis, infarct size was the major independent predictor forearly mortality rate. We conclude that patients who call for an ambulance due to suspectedacute MI appear to have a different early mortality and morbiditypattern compared to those who do not. The most obvious observationwas a higher early mortality. These patients therefore mightbe the most suitable candidates for early intervention studies.     

Corrected TIMI frame counts correlate with stenosis severity and infarct zone wall motion after thrombolytic therapy

BACKGROUND: The majority of patients with patent infarct-related arteries after thrombolytic therapy have slower than normal flow, which relates to myocardial perfusion. METHODS: To evaluate the relationships between blood levels of creatine kinase (CK) and the corrected Thrombolysis in Myocardial Infarction (TIMI) frame count (CTFC), infarct artery stenosis, and left ventricular function, we studied 397 patients with a first myocardial infarction who underwent angiography at 3 weeks. TIMI flow grades, the CTFC, infarct artery stenosis, and infarct zone wall motion (by contrast ventriculography using the centerline method) were assessed, and CK levels (in units per liter) were measured hourly for the first 4 hours after streptokinase (1.5 x 10(6) U over 30-60 minutes) and then every 4 hours over the next 20 hours, all blinded to treatment and outcome. RESULTS: Infarct artery stenosis and the CTFC, assessed as continuous variables, correlated in patients with patent infarct arteries (r = 0.33, P <.001). Also, there was a significant correlation between the CTFC and the sum of hypokinetic chords in the infarct zone (r = 0.15, P =.01). Patients with total occlusion or markedly slowed infarct artery flow (CTFC >100) had a higher fraction of chords with wall motion >2 SDs below normal (0.65 [0.41, 0.80] vs 0.37 [0.0, 0.67]) compared with patients with normal flow (CTFC < or =27) (P <.001). The rates of increase of median CK levels with respect to TIMI flow grades were 342 U/L/h for TIMI 3 versus 212 U/L/h for TIMI 2 versus 140 U/L/h for TIMI 0-1 (P <.0001). CONCLUSIONS: Prolonged corrected TIMI frame counts correlate with stenosis severity in the infarct artery after infarction, infarct zone regional wall motion, and CK levels.     

Anisoylated plasminogen streptokinase complex during the acute phase of myocardial infarction. Results of a multicenter double-blind study versus heparin

Two hundred and thirty-one patients admitted to hospital within 5 hours of the onset of symptoms of a primary myocardial infarction were randomised into 2 groups: one received thrombolytic therapy [anisoylated plasminogen streptokinase activator complex (APSAC): 30 IU in 5 minutes] and the other was given conventional heparin therapy (5,000 IU). Heparin was given to both groups 4 hours later (500 IU/kg/day); the APSAC (N = 119) was identical with respect to age, location of infarct, Killip classification, delay before randomisation (188 +/- 62 minutes). Coronary angiography and ventriculography were performed after 3.4 +/- 1.2 days, and angioscintigraphy and myocardial scintigraphy after 19 +/- 2.5 days to determine the size of the infarct and the quality of left ventricular function. Coronary patency was much higher in the APSAC group (77%) than the heparin group (37%) (p less than 0.001). The angiographic ejection fraction was significantly greater in the thrombolytic group than in the heparin group (53 +/- 13% vs 47 +/- 12%, p less than 0.002), the difference being statistically significant in the anterior and inferior infarct subgroups. At the third week, the difference remained significant in the anterior infarct subgroup: a 31 per cent reduction in necrosed myocardial mass was observed in the APSAC group (33% in anterior infarcts: p less than 0.05 and 16% in inferior infarcts: NS). The limitation of infarct size explained the smaller reduction in left ventricular systolic function (r = 0.73; p less than 0.01). The hospital and one year mortality was comparable in the two groups which was not surprising given the small number of patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Significance of perfusion of the infarct related coronary artery for susceptibility to ventricular tachyarrhythmias in patients with previous myocardial infarction.

OBJECTIVE--To study the significance of perfusion of the infarct related coronary artery for susceptibility to ventricular tachyarrhythmias in patients with a remote myocardial infarction. SETTING--Tertiary referral cardiac centre. METHODS--Angiographic filling of the infarct related artery was assessed in a consecutive series of 85 patients with different susceptibilities to ventricular tachyarrhythmias after previous (> 3 months) Q wave myocardial infarction: 30 patients had a history of cardiac arrest (n = 16) or sustained ventricular tachycardia (n = 14), and sustained ventricular tachyarrhythmia was inducible in these by programmed electrical stimulation (arrhythmia group); 47 patients had no clinical arrhythmic events and no inducible ventricular tachyarrhythmias during programmed ventricular stimulation (control group). Eight patients without a history of any arrhythmic events were inducible into ventricular tachycardia. RESULTS--The patients in the arrhythmia group were older (63 (SD 8) years) than the control patients (59 (6) years, P < 0.05), and had larger left ventricular volumes in cineangiography (P < 0.01), but ejection fraction, severity of left ventricular wall motion abnormalities, previous thrombolytic therapy, and time from previous infarction did not differ between the groups. Patients with susceptibility to ventricular tachyarrhythmias more often had a totally occluded infarct related artery on angiography (77%) than patients without arrhythmia susceptibility (21%) (P < 0.001), and complete collateral filling of the infarct artery in cases without complete anterograde filling was less common in the arrhythmia group than in the control group (P < 0.001). Patients without a history of malignant arrhythmia but with inducible ventricular tachyarrhythmia also had no or poor perfusion of the infarct artery more often than the patients without inducible arrhythmia (P < 0.001). Logistic multiple regression showed that no or poor anterograde or collateral filling of the infarct related artery was the most powerful predictor of susceptibility to ventricular tachyarrhythmias (P < 0.001). Left ventricular size and function were not independently related to arrhythmic susceptibility. CONCLUSIONS--No or poor angiographic filling of the infarct related artery is closely associated with susceptibility to ventricular tachyarrhythmias late after acute myocardial infarction, suggesting that perfusion of the infarct artery will modify favourably the electrophysiological substrate of the infarct scar independently of the myocardial salvage achieved by early reperfusion.     

Streptokinase improves reperfusion blood flow after coronary artery occlusion

Streptokinase is an effective thrombolytic agent which, with early restoration of coronary blood flow, has the potential for limiting infarct size. Distinct from thrombolysis, we studied the effects of streptokinase on reperfusion coronary blood flow and infarct size. Open-chest anesthetized canines underwent a 90 minute snare occlusion of the left circumflex coronary artery followed by release and reperfusion through a critical stenosis for 6 hours. The animals were assigned randomly to two groups. Intracoronary streptokinase [group 1 (n = 8): 6000 IU/kg in 3 ml of saline] or saline [group 2 (n = 8): 3 ml of saline] was infused at 0.05 ml/min for 60 minutes beginning 30 minutes before reperfusion. Coronary blood flow was stable in group 1 during reperfusion, while in group 2 it fell during 6 hours of reperfusion (30 +/- 4 ml/min to 18 +/- 2 ml/min, P = 0.05). The ST-segment elevation on the limb lead II electrocardiogram 15 minutes after coronary artery occlusion was similar in both groups (group 1: 3.9 +/- 0.6 mV, group 2: 2.3 +/- 0.5 mV), suggesting the extent of myocardial ischemia was also similar in both groups. The infarct sizes were similar when expressed both as a percent of the total left ventricular mass [(IZ/LV) group 1: 17 +/- 2.5%, group 2: 17.5 +/- 2.5%] or as a percent of the area at risk of infarction [(IZ/AR) group 1: 39 +/- 6%, group 2: 39 +/- 5%]. In both groups, the mass of left ventricle dependent on the blood flow distribution of the left circumflex coronary artery was similar when compared to total left ventricular mass [(AR/LV) group 1: 41 +/- 3%, group 2: 44 +/- 4%]. These results demonstrate that streptokinase maintains reperfusion coronary blood flow through a critical stenosis at a rate similar to baseline levels. Despite the fact that coronary blood flow remained stable with streptokinase during reperfusion, infarct size was not limited after 90 minutes of fixed coronary artery occlusion in this canine model of myocardial injury.     

Intracoronary thrombolysis in acute myocardial infarction: Duration of ischemia as a major determinant of late results after recanalization

To define the effect of duration of myocardial ischemia on the late results after successful thrombolysis in patients with acute transmural myocardial infarction, data on 39 patients treated with intracoronary infusion of streptokinase were analyzed. Patients with successful recanalization of infarct vessel and a time lag between onset of symptoms and reperfusion less than 4 hours were assembled in group A1 (n = 15) and patients with successful recanalization but a time lag of more than 4 hours (n = 17) in group A2. Group B consisted of 7 patients with unsuccessful thrombolysis. Coronary anatomy, left ventricular volume, ejection fraction and regional ejection fraction of infarct area were determined before and 4 weeks after thrombolysis with cineangiography. Serum creatine kinase activity was serially measured.Before intervention, the groups were comparable with regard to age, Killip class, localization of infarction, incidence of previous infarction, Gensini score of coronary anatomy, left ventricular volume, ejection fraction, regional ejection fraction of infarct area and serum creatine kinase activity. Four weeks after the intervention, patients in group A1 had a higher ejection fraction (59 %) and regional ejection fraction of infarct area (39%) than patients in group A2 (ejection fraction: 49%, p < 0.05; regional ejection fraction: 26%, p < 0.05) and group B (ejection fraction: 44%, p < 0.05; regional ejection fraction: 25%, p = 0.05). Peak serum creatine kinase activity measured during the acute illness was lower in group A1 (764 U/liter) than in group A2 (1,580 U/liter, p < 0.05) and group B (2,106 U/liter, p < 0.05).Thus, contraction of infarct area was improved and enzymatic estimate of infarct size was reduced after early as compared with late reperfusion in patients with acute myocardial infarction.     

Multicenter trial of intravenous anisoylated plasminogen streptokinase activator complex (APSAC) in acute myocardial infarction: effects on infarct size and left ventricular function

Two hundred thirty-one patients with a first acute myocardial infarction were randomly allocated within 5 h after the onset of symptoms either to treatment with anisoylated plasminogen streptokinase activator complex (APSAC), 30 U over 5 min, or to conventional heparin therapy, 5,000 IU in a bolus injection. Heparin was reintroduced in both groups 4 h after initial therapy at a dosage of 500 IU/kg per day. One hundred twelve patients received APSAC and 119 received heparin within a mean period of 188 +/- 62 min after the onset of symptoms. Both groups were similar in age, location of the acute myocardial infarction, Killip functional class and time of randomization. Elective coronary arteriography was performed on an average of 4 +/- 1.2 days after initial therapy. Follow-up radionuclide angiography and thallium-201 single photon emission computed tomography were performed before hospital discharge. Infarct size was estimated from single photon emission computed tomography and expressed as a percent of total myocardial volume. 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 group than in the heparin group. This was true for the entire study group (0.53 +/- 0.13 versus 0.47 +/- 0.12; p = 0.002) as well as for the subgroups of patients with anterior and inferior wall infarction (0.47 +/- 0.13 versus 0.40 +/- 0.11; p = 0.04 and 0.56 +/- 0.10 versus 0.51 +/- 0.11; p = 0.02, respectively). At 3 weeks, the difference remained significant for the anterior myocardial infarction subgroup. A significant 31% reduction in infarct size was found in the APSAC group (33% for the anterior infarction subgroup [p less than 0.05] and 16% for the inferior infarction subgroup [p = NS]). A close inverse relation was found between the values of left ventricular ejection fraction and infarct size (r = -0.73, p less than 0.01). By the end of a 3 week follow-up period, seven APSAC-treated patients and six heparin-treated patients had died. In conclusion, the early infusion of APSAC in acute myocardial infarction produced a high early patency rate, significant limitation of infarct size and significant preservation of left ventricular systolic function, mainly in anterior wall infarction.     

Safety of helicopter transport and out-of-hospital intravenous fibrinolytic therapy in patients with evolving myocardial infarction

Of 150 consecutive patients with acute myocardial infarction transported by helicopter for acute intervention, 55 had intravenous thrombolytic therapy (tissue plasminogen activator in 12, streptokinase in 43) initiated prior to transfer. Patients were transported 55 +/- 10 ground miles in 17 +/- 6 minutes and no patient died or experienced bleeding or hemodynamic instability during transfer. Patients receiving thrombolytic therapy had a higher incidence of arrhythmias during transit compared to the untreated group, ventricular tachycardia in six and third-degree atrioventricular block in one compared to ventricular tachycardia in one patient, respectively (p = 0.005). However, these arrhythmias were transient and did not require cardioversion, temporary pacing, or further antiarrhythmic medical treatment. Chest pain was relieved or decreased more frequently in the patients receiving thrombolytic therapy vs. those untreated; 21 of 55 vs. 21 of 95 respectively (p = 0.04). Immediate coronary angiography confirmed a higher incidence and more complete infarct vessel patency (34/55 vs. 30/95) in the patients receiving tissue plasminogen activator or streptokinase (p less than 0.001). Thus, helicopter transfer of patients with evolving myocardial infarction is safe, and early initiation of thrombolytic therapy is associated with increased infarct vessel patency and benign reperfusion arrhythmias.     

Enhanced thrombolytic efficacy and reduction of infarct size by simultaneous infusion of streptokinase and heparin.

Because paradoxical increase in thrombin activity was reported after the administration of streptokinase in patients with acute myocardial infarction the velocity of reperfusion and degree of myocardial damage were studied when heparin was infused during rather than after streptokinase infusion. Thirty seven consecutive patients with acute myocardial infarction were randomised to receive intravenous heparin during (group 1, n = 18) or after (group 2, n = 19) streptokinase (1.5 megaunits over 60 minutes). Markers of reperfusion were monitored every 15 minutes for 3 hours. The serum concentration of creatine kinase was measured every 2 hours. The two groups were similar in terms of age and sex distribution, infarct site, time to treatment, and baseline myocardial ischaemia. Patients in group 1 had a significantly shorter mean (SD) reperfusion time (57 (35) minutes v 101 (47)). From 60 to 120 minutes after randomisation there were significant differences in ST segment elevation between the groups. Serum creatine kinase MB peaked earlier (8 (2) hours) in group 1 than in group 2 (10 (4) hours). The peak concentration was significantly lower in group 1 (87 (47) mU/ml) than in group 2 (134 (96) mU/ml) and infarcts were smaller (25.2 (9.8) gram equivalents/m2) in group 1 than in group 2 (35.1 (10.2) gram equivalents/m2). Simultaneous infusion of heparin and streptokinase speeds up the appearance of signs of reperfusion and reduces infarct size.     

Enhanced thrombolytic efficacy and reduction of infarct size by simultaneous infusion of streptokinase and heparin

Because paradoxical increase in thrombin activity was reported after the administration of streptokinase in patients with acute myocardial infarction the velocity of reperfusion and degree of myocardial damage were studied when heparin was infused during rather than after streptokinase infusion. Thirty seven consecutive patients with acute myocardial infarction were randomised to receive intravenous heparin during (group 1, n = 18) or after (group 2, n = 19) streptokinase (1.5 megaunits over 60 minutes). Markers of reperfusion were monitored every 15 minutes for 3 hours. The serum concentration of creatine kinase was measured every 2 hours. The two groups were similar in terms of age and sex distribution, infarct site, time to treatment, and baseline myocardial ischaemia. Patients in group 1 had a significantly shorter mean (SD) reperfusion time (57 (35) minutes v 101 (47)). From 60 to 120 minutes after randomisation there were significant differences in ST segment elevation between the groups. Serum creatine kinase MB peaked earlier (8 (2) hours) in group 1 than in group 2 (10 (4) hours). The peak concentration was significantly lower in group 1 (87 (47) mU/ml) than in group 2 (134 (96) mU/ml) and infarcts were smaller (25.2 (9.8) gram equivalents/m2) in group 1 than in group 2 (35.1 (10.2) gram equivalents/m2). Simultaneous infusion of heparin and streptokinase speeds up the appearance of signs of reperfusion and reduces infarct size.     

Evaluation of the efficacy of intravenous fibrinolytic treatment in the acute phase of myocardial infarction. Value of the determination of human plasma cardiac myosin

Following acute myocardial infarction, fragments of human cardiac myosin can be detected in plasma by means of monoclonal antibodies to myosin heavy chains from the left human ventricle. The cumulative amounts of myosin released during the first 9 post-infarction days are proportional to the size of the infarct (Tao Ming et al., in the press). The purpose of our study was to evaluate the effectiveness of a fibrinolytic treatment administered in the acute phase of myocardial infarction by measuring in the plasma, the circulating fragments of human cardiac myosin. Three groups of patients with acute myocardial infarction were investigated: 13 patients (group A) received a conventional treatment; 8 patients (group B) were treated with intravenous streptokinase without success, i.e. with persistence of the coronary occlusion; 9 patients (group C) were successfully treated with intravenous streptokinase, resulting in recanalization of the coronary artery. We found that the cumulative amount of myosin released during the first 9 post-infarction days was significantly lower in patients successfully treated with streptokinase [group C: (3.8 +/- 2.3) 10(3) ng/ml/day]. There was no difference in cumulative release of myosin between control patients [group A: (7.0 +/- 3.3) 10(3) ng/ml/day] and patients with unsuccessful fibrinolytic treatment [group B: (10.0 +/- 4.1) 10(3) ng/ml/day]. These results were unrelated to the localisation of the infarct. It is concluded that measuring the cumulative amounts of myosin released is a means of evaluating the effectiveness of fibrinolytic therapy.(ABSTRACT TRUNCATED AT 250 WORDS)