Acute coronary artery obstruction in myocardial infarction: overview of thrombolytic therapy

Pump failure, ranging from ventricular dysfunction to acute cardiogenic shock, is now the leading cause of cardiac death. Efforts at temporary mechanical or pharmacologic support of the heart have been largely unsuccessful so that attention is now directed toward prevention of ventricular failure and limitation of myocardial infarct size or even outright prevention of infarction itself. In particular, attention has been refocused on earlier reperfusion efforts with streptokinase. 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 (Netherlands Interuniversity Cardiology Institute). Early thrombolytic therapy with intracoronary streptokinase (152 patients) or with intracoronary streptokinase preceded by intravenous streptokinase (117 patients) was compared with 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. Of the patients eligible for this detailed analysis, 245 were allocated to thrombolytic therapy and 243 to conventional treatment. Early angiography was preformed in 212 of the 245 patients allocated to thrombolytic therapy. Patency of the infarct-related artery was achieved in 181 patients (85%). Enzymatic infarct size, measured from cumulative alpha-hydroxybutyrate dehydrogenase release, was smaller in patients allocated to thrombolytic therapy (median 760 versus 1,179 U/liter in control subjects, p = 0.0001). Left ventricular ejection fraction measured by radionuclide angiography before discharge was higher after thrombolytic therapy (median 50% versus 43% in control subjects, p = 0.0001). Twelve month mortality was lower in patients allocated to thrombolytic therapy (8% versus 16% in the control group, p less than 0.01). In multivariate regression analysis infarct size limitation, improvement of left ventricular ejection fraction and 3 month mortality were predicted by sigma 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 a sigma ST segment 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 sigma ST less than 1.2 mV, admitted 2 to 4 hours after onset of symptoms.     

Relation of left ventricular volume and function over one year after acute myocardial infarction to infarct size determined by technetium-99m sestamibi

Twenty patients with a first acute myocardial infarction (AMI) (15 anterior, 5 inferior) who received successful reperfusion therapy underwent tomographic imaging with technetium-99m (Tc-99m) sestamibi and radionuclide ventriculography at discharge, 6 weeks, and 1 year after AMI. Patency of the infarct-related artery after reperfusion (thrombolysis, 8 patients; coronary angioplasty, 12 patients) was confirmed by angiogrpahy in all patients. Tc-99m sestamibi perfusion defect at discharge (a measure of infarct size) was quantitated using previous methods and expressed as a percentage of the left ventricle (28 +/- 19%, range 0 to 59%). This perfusion defect size correlated closely with ejection fraction at discharge (r = -0.87), 6 weeks (r = -0.81) and at 1 year (r = -0.78, all p less than 0.0001). Perfusion defect size at discharge also correlated closely with end-systolic volume index at discharge (r = 0.71, p less than 0.0005), 6 weeks (r = 0.63, p less than 0.005) and at 1 year (r = 0.76, p less than 0.0001). Perfusion defect size at discharge did not correlate significantly with end-diastolic volume index at discharge or at 6 weeks, but did correlate at 1 year (r = 0.66, p less than 0.005). There was no significant group change in end-systolic or end-diastolic volume indexes from discharge to 1 year later, although 7 patients had definite individual changes in end-diastolic volume index (3 increased and 4 decreased). There was no relation between defect size and late changes in end-systolic volume index, but there was a weak correlation between defect size and late changes in end-diastolic volume index (r = 0.42, p = 0.07).(ABSTRACT TRUNCATED AT 250 WORDS)     

Relation of left ventricular dilation during acute myocardial infarction to systolic performance, diastolic dysfunction, infarct size and location

The quantification of left ventricular (LV) volumes and assessment of their relation to systolic and diastolic dysfunction, infarct size and anatomic location were performed in 54 patients with a first acute myocardial infarction (AMI). Blood pool radionuclide angiography was used to assess LV end-diastolic, end-systolic, and stroke volume indexes, ejection fraction and peak diastolic filling rate. Infarct size was estimated from plasma MB creatine kinase activity. Substantial LV dilation occurred within the initial 24 hours of AMI. The peak diastolic filling rate was low, even in those patients with a normal ejection fraction. In comparison with inferior AMI (n = 25), patients with anterior AMI (n = 29) had a larger end-diastolic volume index (105 +/- 8 vs 81 +/- 4 ml/m2, p less than 0.01) and end-systolic volume index (64 +/- 7 vs 37 +/- 4 ml/m2, p less than 0.001), but similar stroke volume index (41 +/- 3 vs 43 +/- 2 ml/m2, difference not significant). No significant relation was noted between infarct size estimated by MB creatine kinase and any volumetric index. On repeat study (day 10 after AMI), end-diastolic and end-systolic volume indexes increased further (p less than 0.05 vs day 1) but ejection fraction and peak diastolic filling rate were unchanged. It was concluded that: (1) LV dilation occurs within hours of AMI in both inferior and anterior AMI, but is more marked in the latter; (2) significant LV diastolic dysfunction is the rule, even in patients with preserved LV systolic function; and (3) LV dilation is an early compensatory mechanism that maintains normal stroke volume, even in patients with severely reduced LV function.     

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.     

Late ventricular dilatation in survivors of acute myocardial infarction

The purpose of this study was to assess the natural course of left ventricular (LV) volumes in the convalescent phase of acute myocardial infarction (AMI). Fifty-seven patients were examined 2 weeks and approximately 1 year after AMI by a radionuclide method allowing determination of absolute LV volumes. After 1 year the patients had fewer clinical and radiologic signs of heart failure, but median end-diastolic volume index had increased from 92 to 112 ml/m2 (p less than 0.001), median end-systolic volume index from 51 to 65 ml/m2 (p less than 0.001) and median stroke volume index from 39 to 47 ml/m2 (p less than 0.001). Patients with first anterior infarcts had significantly greater increases in end-diastolic volume index, end-systolic volume index and stroke volume index than patients with first inferoposterior infarcts. The increase in LV volumes was significantly greater in patients with clinical manifestations of heart failure than in those without these signs. Notably, changes in LV size had an unpredictable effect on LV ejection fraction.     

Infarct size determined by emission computed tomography using 99mTc-PYP: effect of coronary thrombolysis

Emission computed tomography with 99mTc-PYP was used to estimate infarct size in 38 patients with documented acute myocardial infarction. In the present study, the effect of thrombolysis with Urokinase on infarct size and on left ventricular function was assessed. Fourteen patients with acute myocardial infarction who underwent intracoronary thrombolysis within six hours after the onset of symptoms, and 24 patients who underwent conventional therapy were the subjects of this study. Infarct size was measured by drawing a region of interest around the myocardial pyrophosphate uptake for each tomographic slice. The boundary was then defined as 65% of the maximal count within the region of interest as determined by phantom volume studies. The total number of voxels was obtained by adding those in all slices and multiplying the sum by the voxel volume (0.205 ml per one voxel) to determine the infarct volume. Measurement of the 99mTc-PYP uptake on the tomographic image revealed an average infarct size of 100.1 +/- 36.0 ml (ranged 45 to 198). The calculated infarct volume correlated significantly with sigma CPK (p less than 0.01) and with left ventricular ejection fraction (p less than 0.01), but not with the peak CPK. In patients with acute inferior myocardial infarction, the mean infarct volume was 78.4 +/- 29.1 ml in the coronary thrombolysis group, and 105.1 +/- 33.7 ml in the conventional bypass graft treatment group (p less than 0.05). We concluded that successful intracoronary thrombolysis may reduce infarct size. ECT imaging with 99mTc-PYP to determine infarct size may be clinically applicable in patients with acute myocardial infarction.     

Serial myocardial lactate metabolic changes after intracoronary thrombolysis in evolving myocardial infarction

To ascertain whether early intracoronary reperfusion (less than 3 hours) preserves aerobic myocardial metabolism in acute myocardial infarction, serial changes in trans-cardiac lactate extraction after intracoronary thrombolysis were examined in 35 patients with acute anteroseptal myocardial infarction. Eight patients without intracoronary reperfusion served as controls. In the chronic phase, we also observed abnormally contracting myocardial segments as an index of infarct size and the regional ejection fraction as an index of chronic regional cardiac function. In the early reperfusion group (less than 3 hours; 15 cases), positive lactate extraction was restored; there were small abnormally-contracting segments and a high regional ejection fraction. However, the intermediate reperfusion group (3-5 hours; 10 cases) had sustained anaerobic lactate extraction, large abnormally-contracting segments and a low regional ejection fraction. The late reperfusion (greater than 5 hours; 10 cases) group showed apparent aerobic lactate extraction, but had large abnormally-contracting segments and a low regional ejection fraction. Thus, early reperfusion preserves aerobic lactate metabolism and good ventricular function in the chronic phase.     

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.     

Which patients benefit most from early thrombolytic therapy with intracoronary streptokinase?

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. Early thrombolytic therapy with intracoronary streptokinase (152 patients) or with intracoronary streptokinase preceded by intravenous streptokinase (117 patients) was compared with conventional treatment (264 patients). All 533 patients were admitted to the coronary care unit within 4 hr after onset of symptoms indicative of acute myocardial infarction. Four hundred eighty-eight patients were eligible for this detailed analysis, and 245 of these were allocated to thrombolytic therapy and 243 to conventional treatment. Early angiographic examinations were performed in 212 patients allocated to thrombolytic therapy. Patency of the infarct-related artery was achieved in 181 patients (85%). Enzymatic infarct size, as measured from cumulative alpha-hydroxybutyrate dehydrogenase release, was smaller in patients allocated to thrombolytic therapy (median 760 vs 1170 U/liter in control patients, p = .0001). Left ventricular ejection fraction measured by radionuclide angiography before discharge from the hospital was higher after thrombolytic therapy (median 50% vs 43% in control patients, p = .0001). Three month mortality was lower in patients allocated to thrombolytic therapy (6% vs 14% in the control group, p = .006). With the use of multivariate regression analysis, infarct size limitation, improvement in left ventricular ejection fraction, and three month mortality were predicted by sum of the ST segment elevation, time from onset of symptoms to admission, and Killip class at admission. Thrombolysis was most effective in patients admitted within 2 hr after onset of symptoms and in patients with a sum of ST segment elevation 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 a sum of ST segment elevation of less than 1.2 mV who were admitted between 2 and 4 hr after onset of symptoms.     

Recovery of left ventricular wall motion in early periods by successful reperfusion following myocardial infarction]

To study the time course and recovery of left ventricular (LV) function after reperfusion therapy (PTCR or PTCA), we recorded 2 D E in 1, 3, 5, 7, 14, 28 days following myocardial infarction in 41 cases with complete occlusion of left anterior descending artery. LV volumes and regional wall motion were analyzed by the centerline method (100 chords) between a reperfused (R) and a non-R group. LV end-diastolic volumes of R increased from 3 to 7 days were smaller than those in non-R. LV end-systolic volume of R decreased during the same periods were also smaller than those of non-R. Besides global ejection fractions of R were larger significantly (p less than 0.05) than those of non-R. Moreover mean percent fractional shortening of infarct-related chords from anteroseptum (-15) to lateral wall (61-80) in R improved more than those in non-R. In conclusion, LV function following myocardial infarction can be assessed by quantitative 2D echo and improved early, and become constant 7 days after successful reperfusion therapy.     

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.     

Reperfusion of the infarct-related coronary artery limits left ventricular expansion beyond myocardial salvage.

Previous echocardiographic data from the Gruppo Italiano per lo Studio della Streptochinasi nell' Infarto Miocardico (GISSI 1) trial suggest that the relation between left ventricular end-systolic volume and infarct size could be altered by thrombolysis, which would exert a restraining effect on end-systolic volume beyond its reducing effect on infarct size. Thus in 63 patients with one-vessel disease and a recent anterior myocardial infarction, we tested at angiography (1) if perfusion of the anterior descending coronary artery exerts any restraining effect on end-systolic volume above and beyond infarct size reduction and (2) if ejection fraction reflects such an additional, beneficial difference in the ventricular remodeling process. End-systolic volume was calculated using the Dodge method and the right anterior oblique projection, while infarct size was quantified according to the number of ventricular radii whose percent shortening fell below the mean -2 SD of a group of normal individuals. Patients were then divided into two groups according to the perfusion status of the vessel using Thrombolysis in Myocardial infarction (TIMI) criteria (TIMI grade 0 to 1: nonperfused vessel, 27 patients; TIMI grade 2 to 3: perfused vessel, 36 patients). For both groups there was a significant linear relation (p less than 0.001) between end-systolic volume and infarct size; as in our echocardiographic data, the regression lines relating volume to infarct size showed a different slope in the two populations so that, for large and matched infarcts, end-systolic volume was smaller in patients with a perfused vessel (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of intracoronary thrombolysis on infarct size and left ventricular function in patients with anterior myocardial infarction--enzymatic, electrocardiographic, radionuclide and hemodynamic evaluations

The influence of the duration of ischemia on infarct size and left ventricular function (LV) was assessed in 30 patients with a first anterior myocardial infarction (MI) and intracoronary thrombolysis (ICTL) on admission. The occlusion time of the left anterior descending coronary artery (LAD) was 4 hours or less in 11 patients (group I), 4-10 hours in 11 (group II) and 10 hours or more in eight (group III). Serial measurements of serum creatine kinase-MB were carried out during the acute phase. Four weeks after the procedure, electrocardiographic pathological Q waves on 34-lead precordial mapping were scored, viable left ventricular myocardial volume and the ratio of infarcted to total left ventricular myocardial volume was estimated by myocardial emission computed tomography (ECT) with thallium-201. In the acute phase enzymatic estimation of infarct size showed a significant difference between group I and the other two groups but not between groups II and III; there were no significant differences in the degree of left ventricular asynergy among the three groups. In the chronic phase infarct sizes evaluated by both Q wave mapping and ECT were smaller in group I than those in group II, which were smaller than those in group III; there were significant differences in the degree of LV asynergy among the three groups (group I less than II less than III). LV function was nearly normal in group I, moderately impaired in group II, but severely depressed in group III 4 weeks later. The present study indicates that infarct size extends and LV function deteriorates with the duration of occlusion of the LAD and that not only early (less than or equal to 4 hours) but also later (4-10 hours) reperfusion is beneficial to prevent the extension of MI and deterioration of LV function in patients with anterior MI.     

Effects of coronary artery reperfusion on relation between creatine kinase-MB release and infarct size estimated by myocardial emission tomography with thallium-201 in man

The quantitative relations between serum creatine kinase-MB isoenzyme (CK-MB) release and the final infarct size estimated by myocardial emission computed tomography with thallium-201 was assessed in 37 patients with a first acute transmural myocardial infarction who underwent intracoronary thrombolysis using urokinase 4.6 +/- 1.9 hours after the onset of symptoms. Serial CK-MB determinations were used to calculate the accumulated release of CK-MB (sigma CK-MB). Myocardial emission tomography with thallium-201 was performed 4 weeks after the onset, and infarct volume was measured from reconstructed tomographic images by computerized planimetry. The results are presented for two groups of patients: 11 patients with unsuccessful thrombolysis (group A) and 26 patients with successful thrombolysis (group B). An excellent linear relation was found for group A (sigma CK-MB = 6.4 X infarct volume + 47.7, r = 0.91), whereas a different linear relation was observed for group B (sigma CK-MB = 10.5 X infarct volume + 89.1, r = 0.80). Moreover, serum CK-MB activity reached a peak at 21.1 +/- 2.2 hours after the onset in group A and reached an earlier peak at 12.5 +/- 2.9 hours in group B (p less than 0.001). These data suggest that acute coronary recanalization alters the kinetics of CK-MB release, resulting in greater CK-MB release into the serum for equivalent infarct volume estimated by myocardial emission tomography with thallium-201. Thus, serum CK-MB time-activity curves after acute myocardial infarction may be influenced considerably by acute reperfusion, which is an important factor that should be incorporated in the interpretation of enzymatic estimates of infarct size in human patients.     

Regional left ventricular function assessed by contrast angiography in acute myocardial infarction.

The relationship of segmental left ventricular (LV) wall motion abnormalities to LV function 2-6 days after acute transmural myocardial infarction (MI) was investigated in 45 patients by quantitative contrast ventriculography. Patients were divided into four classes according to the MIRU criteria. Segmental wall motion was assessed by determining the percentage of systolic shortening (deltaS) along nine hemiaxes and the extent of akinetic or dyskinetic abnormally contracting segments (% ACS) expressed as a percentage of end-diastolic perimeter. When compared with that in 17 normal control-subjects, the LV end-diastolic volume was increased only in patients in class III and class IV; the LV end-systolic volume increased progressively from normal through class IV. Ejection fraction had a negative linear correlation with %ACS (r = 0.97). The size of ACS was larger in anterior (34 +/- 14%) than in inferior MIs (23 +/- 7%), resulting in greater LV dysfunction. However, for a comparable size of ACS, infarct location alone did not influence LV function parameters. In the noninfarcted zone, deltaS was increased when the size of ACS was less than 25% and reduced when the size of ACS was greater than 25%. Thus, the size of ACS is a major determinant of LV dysfunction in acute MI. The compensatory mechanisms operate either through an augmented mechanical function of residual myocardium when the infarct is small, or through the Frank-Starling mechanism when the infarct is large.     

Impact of late coronary artery reperfusion on left ventricular function one month after acute myocardial infarction (results from the ISAM study)

To evaluate the impact of late reperfusion of an infarct-related coronary artery on left ventricular (LV) function in the month after myocardial infarction, findings from 368 patients in the Intravenous Streptokinase in Myocardial Infarction study are presented. All patients had a late peaking in the creatine kinase-MB serum time-activity curve, suggesting absence of early reperfusion. Contrast angiography was performed 1 month after the acute event. The infarct-related coronary artery was patent in 74 of 116 (64%) streptokinase-treated patients and 141 of 252 (56%) patients treated with anticoagulant therapy (placebo group). In all baseline variables, including the actually developed enzymatic and electrocardiographic infarct sizes, there were no differences between the patent- or occluded-artery groups. A patent infarct artery 1 month after infarction was associated with significantly better LV function regardless of the vessel involved and whether or not patients had been treated with streptokinase. Ejection fraction in patients with patent versus occluded artery was 56 +/- 13 versus 50 +/- 14 (p less than 0.0005). Most benefit was noted in patients in whom the proximal left anterior descending coronary artery was affected: ejection fraction was 52 +/- 14 versus 36 +/- 12% (p less than 0.0005). Our data confirm that restoration of adequate flow through an infarct-related coronary artery beyond the time window for actual salvage of ischemic myocardium has a definite beneficial effect on LV function.     

Early recovery of left ventricular function after thrombolytic therapy for acute myocardial infarction: an important determinant of survival

Thrombolytic therapy for acute myocardial infarction reduces early mortality, but full recovery of left ventricular function after reperfusion is delayed. Therefore, the relations among reperfusion, survival and the time course of left ventricular functional recovery were examined in 226 patients treated with intracoronary streptokinase; 77% (134 patients) had sustained reperfusion and 31 patients had no reperfusion or had reocclusion by day 3. Wall motion was measured from contrast ventriculograms performed in the acute period and 3 days later in the central and peripheral infarct regions and the noninfarct region by the centerline method in 165 patients. Patients with reperfusion had better survival (p less than 0.05, mean follow-up 4.5 years) and a higher ejection fraction at 3 days (52 +/- 12 versus 46 +/- 10%, p less than 0.02) attributable to a significantly different change in peripheral infarct region function between the acute and 3 day studies (0.1 +/- 1.0 versus -0.3 +/- 0.9 SD, p less than 0.05). These early functional changes were significant in patients with anterior myocardial infarction and showed similar trends in those with inferior myocardial infarction. On Cox regression analysis, function measured at 3 days was more predictive of survival than was function measured acutely (chi square for acute ejection fraction = 11.48 versus 24.59 at 3 days). Although, as previously reported, greater than 45% of total recovery of left ventricular function occurs later, the ejection fraction achieved by day 3 is already predictive of survival. Thus, the mechanism by which successful thrombolytic therapy enhances survival is improvement of regional and global left ventricular function early after acute myocardial infarction.     

Effects of early intracoronary streptokinase on infarct size estimated from cumulative enzyme release and on enzyme release rate: a randomized trial of 533 patients with acute myocardial infarction

The effects of early intracoronary streptokinase (SK) on enzymatic infarct size and rate of enzyme release were studied in a randomized multicenter trial. A total of 533 patients with acute myocardial infarction (AMI) were allocated to either the SK treatment group (n = 269) or the conventional (control) treatment group (n = 264). Enzymatic infarct size was represented by the cumulative quantity of alpha-hydroxybutyrate dehydrogenase (HBDH) released by the heart per liter of plasma in the first 72 hours. Rate of enzyme release was represented by the ratio of HBDH quantities released in 24 hours and 72 hours. On an "intention to treat" basis, the SK group had a smaller (by 30%; p = 0.0001) median enzymatic infarct size and a higher (by 35%; p = 0.0001) median rate of enzyme release than the control group. Limitation of infarct size was less apparent in patients treated with intracoronary SK only (25%) than in patients treated with intravenous plus intracoronary SK (34%). Compared to the control group, the enzyme release rate in patients treated with intracoronary SK only was slightly less (34%) than that in patients treated with intravenous plus intracoronary SK (38%). Patients with a patent infarct-related coronary artery at acute angiography had a median infarct size which was 55% (p = 0.0001) smaller than the median infarct size of the control group, and the median rate of enzyme release was 38% (p = 0.001) higher than the median release rate of the control group. Patients with successful recanalization during intracoronary SK infusion had a median infarct size which was 31% (p = 0.002) smaller than the median infarct size of the control group and a median rate of enzyme release which was 42% (p = 0.0001) higher than the median release rate of the control group. Patients with persistent coronary occlusion in spite of thrombolytic therapy had a median infarct size which was 11% (NS) higher than the median infarct size of the control group, although the median rate of enzyme release was still 23% (p = 0.02) higher than the median release rate of the control group. It is concluded that thrombolysis in the early phase of AMI limits infarct size and that intracoronary SK treatment itself accelerates the process of enzyme release from infarcted myocardium, independent of the angiographic result.     

Intracoronary transplantation of non-expanded peripheral blood-derived mononuclear cells promotes improvement of cardiac function in patients with acute myocardial infarction.

BACKGROUND: Transplantation of non-expanded peripheral blood mononuclear cells (PBMNCs) enhances neovessel formation in ischemic myocardium and limbs by releasing angiogenic factors. This study was designed to examine whether intracoronary transplantation of PBMNCs improves cardiac function after acute myocardial infarction (AMI). METHODS AND RESULTS: After successful percutaneous coronary intervention (PCI) for a ST-elevation AMI with occlusion of proximal left anterior descending coronary artery within 24 h, patients were assigned to either a control group or the PBMNC group that received intracoronary infusion of PBMNCs within 5 days after PCI. PBMNCs were obtained from patients by COBE spectra-apheresis and concentrated to 10 ml, 3.3 ml of which was infused via over-the-wire catheter. The primary endpoint was the global left ventricular ejection fraction (LVEF) change from baseline to 6 months' follow-up. The data showed that the absolute increase in LVEF was 7.4% in the control group and 13.4% (p=0.037 vs control) in the PBMNC group. Cell therapy resulted in a greater tendency of DeltaRegional ejection fraction (EF) or significant improvement in the wall motion score index and Tc-99m-tetrofosmin perfusion defect score associated with the infarct area, compared with controls. Moreover, intracoronary administration of PBMNCs did not exacerbate either left ventricular (LV) end-diastolic and end-systolic volume expansion or high-risk arrhythmia, without any adverse clinical events. CONCLUSION: Intracoronary infusion of non-expanded PBMNCs promotes improvement of LV systolic function. This less invasive and more feasible approach to collecting endothelial progenitor cells may provide a novel therapeutic option for improving cardiac function after AMI.     

Effects of reperfusion on left ventricular ejection fraction and volume after acute myocardial infarction.

The effects of reperfusion on left ventricular (LV) function and volume were studied in patients with evolving acute myocardial infarction (AMI). We analyzed the LV ejection fraction and volume in patients who had been admitted within 24 h of the onset of their first AMI with culprit lesion of #6, #7 and #1 (American Heart Association classification). Sixty-five patients (Re group) received successful reperfusion therapy within 6 h after the AMI. The other 60 patients (Oc group), who were admitted from 6 to 24 h after the AMI, received conservative therapy. Patients with re-obstruction of the culprit lesion after reperfusion therapy were excluded from the Re group. Patients with spontaneous recanalization following conservative therapy were excluded from the Oc group. The LV ejection fraction (LVEF), LV end-systolic volume index (LVESVI), and LV end-diastolic volume index (LVEDVI) were measured using a modified Dodge's formula by left ventriculography performed 4 weeks after the AMI. LVEF in the Re group was significantly greater than in the Oc group (57 +/- 12 vs 49 +/- 11%) (mean +/- SD, p less than 0.01). LVESVI in the Re group was significantly smaller than in the Oc group (30 +/- 13 vs 38 +/- 16 ml/m2, p less than 0.01). Although LVEDVI was not significantly different between the 2 groups, in patients with a responsible coronary lesion of segment #6, LVEDVI in the Re group was significantly smaller than in the Oc group (67 +/- 14 vs 77 +/- 18 ml/m2, p less than 0.05). Although LVEF and LV volume correlated in both groups, the correlation was weak (r = 0.40-0.42), suggesting that LV volume was not dependent solely on LV functional recovery. The incidence of ventricular aneurysm in the Re group was significantly lower than in the Oc group (15.4 vs 45.0%, p less than 0.01). Multivariate analysis selected reperfusion of the responsible coronary artery as one of the factors significantly associated with a reduction of LVEDVI, LVESVI, an improvement of LVEF, and a decrease in the rate of aneurysm formation. In summary, our results indicated that reperfusion improved EF, reduced LV volume, and decreased the rate of aneurysm formation as compared to non-reperfusion, which suggests that reperfusion therapy is beneficial for both functional recovery and ventricular remodeling.