尿激酶及阿司匹林对血浆α-颗粒膜蛋白140的影响及意义

目的：探讨急性心肌梗塞（ＡＭＩ）患者尿激酶静脉溶栓及阿司匹林口服治疗前后血小板活性的动态变化及与血管再通的关系。方法：８０例ＡＭＩ患者,随机分成溶栓组及溶栓＋阿司匹林组各４０例,于溶栓前及溶栓后２、６、１２、２４小时测定血浆中α－颗粒膜蛋白１４０（ＧＭＰ－１４０）浓度,依临床间接指标（３８例行冠状动脉造影）判定血管再通,比较两组间及两组中再通与未通患者血浆ＧＭＰ－１４０浓度的动态变化。正常对照组６０例。结果：ＡＭＩ患者溶栓前后血浆ＧＭＰ－１４０浓度均明显高于正常对照组。两个溶栓组溶栓后再通与未通患者均呈现不同浓度的动态变化。血管再通,则血浆ＧＭＰ－１４０浓度降低,血管未通,血浆ＧＭＰ－１４０浓度升高;阿司匹林对血浆ＧＭＰ－１４０浓度无影响。结论：ＡＭＩ后血小板高度活化,血浆ＧＭＰ－１４０浓度与血栓形成、溶解及再通密切相关;阿司匹林不是抑制血小板活化的理想药物。     

Reperfusion alters the relation between blood flow and the remaining myocardial infarction

This study evaluated whether or not reperfusion of ischemic myocardium 2 hours after occlusion alters the basic relation between myocardial blood flow and infarction occurring during permanent occlusion. Awake mongrel dogs chronically instrumented with proximal circumflex coronary occluders were subjected to permanent occlusion (group A, n = 10) or occlusion followed by reperfusion 2 hours later (group B, n = 11). Myocardial blood flow was quantified with radioactive microsphere injections before, 6 hours after occlusion (group A), immediately before release, and 4 hours after reperfusion (group B). Three days later, the dogs were killed, and the heart was sectioned systematically into approximately 80 1-2-g circumferential and transmural samples for radioactive counting and histologic infarct quantification. Epimyocardial and endomyocardial samples from the permanent occlusion group (A) and the reperfused group (B) were separated by infarct range and related to regional myocardial blood flow measurements. In groups A and B, regional myocardial blood flow in endomyocardial and epimyocardial layers were inversely related to the extent of infarction. For given degrees of infarction, myocardial blood flow was significantly higher (greater than twofold) in the reperfused group. Myocardial samples with extensive infarction (51-75%) showed only mild (20-30%) reductions in blood flow when compared with nonischemic regions in the reperfused group. Thus, although early reperfusion may salvage ischemic myocardium, these studies showed that reperfusion causes a new relation between blood flow to the ischemic region and eventual histologic infarct size. When myocardial blood flow is used as an index of myocardial salvage after reperfusion, the basic relation obtained from permanent occlusion studies substantially overestimates the extent of myocardial salvage and underestimates the degree of remaining infarction.     

Effect of intracoronary adenosine infusion during coronary intervention on myocardial reperfusion injury in patients with acute myocardial infarction

Despite early recanalization of an occluded infarct artery, up to 33% of patients with acute myocardial infarction do not obtain complete myocardial reperfusion due to a process of reperfusion injury. This study assessed whether adjunctive therapy with adenosine might prevent or attenuate the phenomenon of myocardial reperfusion injury. Myocardial reperfusion was assessed in 79 consecutive patients receiving a 20-minute intracoronary infusion of adenosine during percutaneous coronary intervention (PCI) and in a historical cohort of 200 patients with acute myocardial infarction who were treated with PCI (controls). Myocardial reperfusion injury was defined as persistent (> or =50% of initial value) ST-segment elevation after successful recanalization. Its effect on infarct size was evaluated by calculating the Selvester QRS score before intervention and at follow-up. Myocardial reperfusion injury was present in 19% of patients receiving adenosine versus 35% of control patients (p = 0.004). Evaluation of infarct expansion over time showed almost no change in the QRS score in patients receiving adenosine (3.4 +/- 3.0 before PCI; 3.5 +/- 3.1 at follow-up). In contrast, infarct QRS score in the control group worsened from 3.1 +/- 2.7 before PCI to 4.5 +/- 3.2 at follow-up (p = 0.003 treatment with adenosine vs control). Multivariate analysis identified adjunctive therapy with adenosine as an independent protective determinant of myocardial reperfusion injury and of infarct expansion. The rate of major adverse cardiac events (death and myocardial infarction) at 1 month tended to be lower in patients receiving adenosine (4% vs 6.5%, p = 0.7) and was mainly observed in patients with evidence of myocardial reperfusion injury (cardiac event rate 2% in patients with ST-segment elevation of <50% vs 14% in patients with ST-segment elevation > or =50%, p = 0.003). Thus, impaired myocardial reperfusion is the most important determinant of clinical outcome in patients with acute myocardial infarction treated with PCI. Adjunctive therapy with intracoronary infusion of adenosine during PCI prevents the occurrence of severe myocardial reperfusion injury and is associated with less infarct expansion.     

Importance of myocardial infarct artery patency on the prevalence of ventricular arrhythmia and late potentials after thrombolysis in acute myocardial infarction.

Sustained infarct artery patency is an important determinant of survival in patients with acute myocardial infarction. We studied 61 patients with acute myocardial infarction who received intravenous recombinant tissue-type plasminogen activator, aspirin or heparin within 6 hours of symptom onset, to determine if infarct artery patency after intravenous thrombolytic therapy influences myocardial electrical stability as measured by the prevalence of spontaneous ventricular ectopy or late potential activity. Infarct artery patency was determined by angiographic evaluation 2.5 +/- 3 days after infarction. Forty-eight patients (79%) had a patent infarct-related artery and 13 (21%) patients had an occluded vessel. The mean number of ventricular premature complexes (VPCs)/hour (p less than 0.01) and the prevalence of late potentials (54 vs 19%; p less than 0.03) were significantly higher in patients with an occluded versus patent-infarct related vessel. Although VPC frequency and late potentials were not influenced by the time to thrombolytic treatment, patients with a patent infarct-related artery had a lower prevalence of late potentials regardless of whether treatment was initiated less than or equal to 2 hours (25% patent vs 50% occluded; p = not significant) or 2 to 6 hours (16% patent vs 55% occluded; p greater than 0.03) after symptom onset. Thus, successful thrombolysis decreases the frequency of ventricular ectopic activity and late potentials in the early postinfarction phase. The reduction in both markers of electrical instability may help explain why the prognosis after successful thrombolysis is improved after acute myocardial infarction.     

Effects of thrombolytic therapy on evolution of left ventricular function in acute myocardial infarction

Use of thrombolytic therapy in the early hours of acute myocardial infarction (AMI) has gained widespread acceptance. One potential benefit of early reperfusion could be improved left ventricular (LV) function. Experimental animal studies have demonstrated that duration of coronary occlusion determines ultimate infarct size and have also raised the issue of reperfusion injury. The evolution of LV function after AMI in man where there is no attempt at early reperfusion is discussed. Studies of LV function following thrombolytic therapy in man have illustrated the following points. Time to successful reperfusion appears to be a critical determinant for potential for LV functional recovery. If reperfusion is achieved within 2.5 hours after onset of symptoms, consistent recovery of function within the infarct zone appears to be possible. With reperfusion from 2.5 to six hours after onset of symptoms, there is no predictable, substantial improvement in either global or regional LV function. Within the framework of this general conclusion, there are three potential exceptions: Successful reperfusion up to six hours after onset of symptoms may prevent infarct expansion. Patients with subtotal occlusion of the infarct vessel prior to therapy in this time period may have more potential for recovery of LV function than those with initial total occlusion. A tight residual stenosis following thrombolytic therapy may mask potential for functional recovery in the infarct zone. Earlier diagnosis and treatment of AMI is one obvious solution for the overall lack of beneficial results on evolution of LV function seen in most studies to date.(ABSTRACT TRUNCATED AT 250 WORDS)     

Are enzymatic tests good indicators of coronary reperfusion?

OBJECTIVE--To assess the accuracy of four enzymatic tests, including early release rates of creatine kinase and alpha-hydroxybutyrate dehydrogenase, in assessing coronary reperfusion after thrombolytic therapy. DESIGN--A prospective clinical trial identifying patients with a successful thrombolytic treatment. PATIENTS--Eighty nine patients with acute myocardial infarction were studied. Arteriography showed a closed infarct related artery in all of them. Reperfusion due to thrombolysis occurred in 74 patients and there was no reperfusion in 15 patients. RESULTS--The 74 patients showing coronary reperfusion had a significantly shorter time to peak creatine kinase activity, higher early release rates for creatine kinase and alpha-hydroxybutyrate dehydrogenase, and a more rapid release of alpha-hydroxybutyrate dehydrogenase (ratio of cumulative release of alpha-hydroxybutyrate dehydrogenase during the first 24 hours to that 72 hours after infarction). All these differences were statistically significant (p less than 0.001). Optimum cut off levels were determined with decision level plots and the accuracy of the four enzymatic tests was calculated. Accuracy was low for all four tests (73%, 70%, 70%, and 82%). CONCLUSION--None of the four enzymatic tests accurately predicted the perfusion state of the infarct related coronary artery after thrombolysis. These tests cannot be used reliably in routine clinical practice as non-angiographic markers of coronary reperfusion.     

Are enzymatic tests good indicators of coronary reperfusion?

OBJECTIVE--To assess the accuracy of four enzymatic tests, including early release rates of creatine kinase and alpha-hydroxybutyrate dehydrogenase, in assessing coronary reperfusion after thrombolytic therapy. DESIGN--A prospective clinical trial identifying patients with a successful thrombolytic treatment. PATIENTS--Eighty nine patients with acute myocardial infarction were studied. Arteriography showed a closed infarct related artery in all of them. Reperfusion due to thrombolysis occurred in 74 patients and there was no reperfusion in 15 patients. RESULTS--The 74 patients showing coronary reperfusion had a significantly shorter time to peak creatine kinase activity, higher early release rates for creatine kinase and alpha-hydroxybutyrate dehydrogenase, and a more rapid release of alpha-hydroxybutyrate dehydrogenase (ratio of cumulative release of alpha-hydroxybutyrate dehydrogenase during the first 24 hours to that 72 hours after infarction). All these differences were statistically significant (p less than 0.001). Optimum cut off levels were determined with decision level plots and the accuracy of the four enzymatic tests was calculated. Accuracy was low for all four tests (73%, 70%, 70%, and 82%). CONCLUSION--None of the four enzymatic tests accurately predicted the perfusion state of the infarct related coronary artery after thrombolysis. These tests cannot be used reliably in routine clinical practice as non-angiographic markers of coronary reperfusion.     

Intracoronary thrombolysis and early bypass surgery for acute myocardial infarct: five years' experience

During the five-year period between March 1980 and February 1985 selective intracoronary thrombolysis with streptokinase was performed in 469 patients with clinical and ECG signs of acute transmural myocardial infarct. Coronary arteriography prior to thrombolysis showed the infarct related vessel still or again patent in 21% of the patients. Among 372 patients with complete occlusion streptokinase infusion was successful in 87%, but failed in 13%. Due to the high risk of reocclusion, early bypass surgery was performed in 69 patients (18.5%) of the successfully reperfused group. Indication was based primarily on an ischemic time interval of less than 4 hours between the acute onset of clinical symptoms and reperfusion. Early mortality was 1.5% in this surgically treated group and actuarial survival was 92% at 5 years with all but 3 patients in functional class I or II. Marked but non-fatal early congestive heart failure was more significant when patients underwent operation within the first 2 days after thrombolysis than thereafter. Late recatheterization studies in 29 patients showed a slight but statistically insignificantly higher occlusion rate for vein grafts to the infarct vessel (14%) than to concomitantly grafted arteries (6%). No correlation was found between the initial ischemic time interval and graft patency. Late left ventricular function was excellent or minimally impaired in 52% of these patients while 48% had significantly reduced LV function. Again, no correlation was found between the ischemic time interval and late LV function. LV aneurysm, however, occurred only in patients with an ischemia of more than 3 hours. Thrombolysis combined with early bypass surgery represents the optimal therapy for acute myocardial infarct.(ABSTRACT TRUNCATED AT 250 WORDS)     

Long-term prognosis of late spontaneous reperfusion after failed thrombolysis for acute myocardial infarction

BACKGROUND: Early reperfusion improves left ventricular (LV) function and survival after acute myocardial infarction (MI). Thrombolytic therapy achieves early patency of the infarct artery in about two-thirds of patients. In nearly half of the remaining patients, in whom early reperfusion was not achieved with thrombolytic therapy, the infarct artery might reopen by the time of predischarge angiography. However, the impact of such late spontaneous reperfusion after failed thrombolytic therapy on LV function and long-term survival remained unclear. HYPOTHESIS: This study was undertaken to assess implication of late spontaneous reperfusion after failed thrombolytic therapy on LV function and long-term survival after acute MI. METHODS: The study consisted of 198 patients with anterior acute MI who underwent thrombolytic therapy and predischarge angiography: 160 patients with infarct artery patent early and late after therapy (persistent patency), 17 patients with infarct artery occluded early after therapy but patent at predischarge angiography (late spontaneous reperfusion), and 21 patients with infarct artery occluded early and late after therapy (persistent occlusion). RESULTS: Persistent patency was associated with enhanced improvement in LV ejection fraction (7.7 +/- 11.8%) compared with late spontaneous reperfusion (0.0 +/- 9.6%, p = 0.03) and persistent occlusion (-1.4 +/- 9.7%, p = 0.003). Persistent patency was associated with better long-term survival than with late spontaneous reperfusion (p < 0.001) and persistent occlusion (p < 0.001). Multivariate analysis comparing persistent patency and late spontaneous reperfusion showed that early reperfusion was an independent predictor of long-term survival. CONCLUSION: Late spontaneous reperfusion after failed thrombolytic therapy was associated with poor LV function and long-term survival, emphasizing the importance of early reperfusion.     

Possible survival benefit from concomitant beta-but not calcium-antagonist therapy during reperfusion for acute myocardial infarction

To test the hypothesis that long-term beta- or calcium-antagonist therapy begun before the time of myocardial infarction and coronary reperfusion might improve patient in-hospital survival compared with reperfusion alone, 424 consecutive patients successfully reperfused with coronary angioplasty within 12 hours of infarct symptom onset were carefully and retrospectively characterized. Forty-seven patients (11%) were taking beta antagonists and 74 patients (17%) were taking calcium antagonists at the time of infarction. Patients receiving beta antagonists had a more frequent history of hypertension (p less than or equal to 0.001) and prior infarction (p less than or equal to 0.01) than those not so treated and patients receiving calcium antagonists had a more frequent history of prior infarction, prior angina, hypertension and diabetes (all p less than or equal to 0.001) than their nontreated counterparts. Stepwise logistic regression analysis found significant independent correlations between in-hospital death and the following variables: recurrent ischemia (p less than or equal to 0.001); proximal left anterior descending coronary infarct (p less than or equal to 0.001); 3-vessel disease (p = 0.002); patient age (p = 0.004); and initial total occlusion of the infarct artery (p = 0.022). After adjustment for these factors, beta antagonist use (mortality = 0 vs 8% without treatment) was still significantly correlated with improved survival (p = 0.048), whereas calcium-antagonist therapy made no difference in survival. Heart rate and left ventricular end-diastolic pressure upon presentation were significantly lower in patients treated with beta antagonists. Thus, beta-antagonists therapy, but probably not calcium-antagonist therapy, taken before reperfusion for acute myocardial infarction, may improve early survival compared to reperfusion alone. Larger studies will be required to confirm or refute these observations.     

A clinical study of the relation between time to reperfusion and infarct size

Observations made in animal models of reperfusion in acute myocardial infarction have shown that early reperfusion results in myocardial salvage. But the relation between the time of reperfusion and myocardial salvage is not clear in human patients. If earlier reperfusion provides smaller infarct size, reperfusion therapy initiated in the first 1 hour should be the most beneficial. In this study, we compared the results of therapy initiated in the first 1 hour (group A, n = 19) with treatment started 1 to 24 hours after the onset of chest pain (group B, n = 652). The infarct location, development of collateral vessels, number of diseased vessels and reperfusion rate of thrombolysis in the two groups didn't differ. There was a statistically insignificant trend towards total occlusion of the infarct artery in group A (89.5% vs 69.7%, p less than 0.1). Peak CPK and changes in left ventricular ejection fraction (delta EF) were assessed in patients with total occlusion of the left anterior descending artery and successful reperfusion (n = 8 in group A, n = 120 in group B). There was no difference in peak CPK (3281 +/- 2192Iu/l vs 3490 +/- 1811Iu/l) and delta EF (6.3 +/- 17.1% vs 5.8 +/- 11.9%). These findings suggest that there is no relation between the time of reperfusion and myocardial salvage in human patients.     

Preservation of global and regional left ventricular function after early thrombolysis in acute myocardial infarction

The effect of early myocardial reperfusion (within 4 hours after onset of symptoms) on regional left ventricular function in patients with acute myocardial infarction has been quantitated by analysis of segmental wall motion. Of 533 patients randomized either to conventional coronary care unit therapy or to a reperfusion strategy, in 332 high quality angiograms were obtained 2 to 8 weeks after the onset of myocardial infarction. In those assigned to thrombolytic therapy, angiographic data were also available after acute reperfusion. Analysis on an "intention to treat" basis revealed significant preservation of left ventricular function after thrombolytic therapy (ejection fraction 53%) compared with conventional treatment (ejection fraction 47%). In addition, wall motion analysis showed significant improvement of regional function in the infarct zone in both inferior and anterior infarction. In addition, significant changes occurred in regional function of the remote "noninfarct zone" in the acute as well as the chronic stage. It is concluded that improved regional and global left ventricular function can be achieved with early reperfusion and that this is the likely explanation for the reduction of early and late mortality after thrombolysis observed in this study.     

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.     

Enzymatische Marker der Reperfusion bei akutem Myokardinfarkt

Despite advances in therapy acute myocardial infarction is associated with a mortality rate of up to 30%. Early and complete reperfusion of the infarct related artery (defined as TIMI flow 3 at 90 minutes following therapy) as obtained with thrombolytic therapy in 50 to 80% of patients improves survival and enhances ventricular function. Failure to achieve recanalization should prompt further intervention (second attempt of thrombolysis or rescue-PTCA). Various cardiac markers known from diagnosing acute myocardial infarction or risk stratification in unstable angina pectoris have been assessed in their ability to predict successful reperfusion/failure of therapy. Following reperfusion creatinkinase (CK) and its isoform CK-MB, troponin and myoglobin show an early and rapid rise to a high maximum value with rapid normalization. For creatinkinase time to peak values of less than 9 hours or rates of increase of > 50 U/h (> or = 10 U/h for CK-MB activity) within the first 2.5 hours following thrombolysis have been suggested as useful indicators of successful reperfusion. The same applies for a troponin (T)slope > 0.5 ng/ml/h within the first hour (Table 5). The major limitation in applying either creatinkinase, troponin or even lactatdehydrogenase (LDH) is their comparatively late release (4 to 6 hours) following myocardial infarction. In that respect myoglobin (though not specific for cardiac injury) seems ideal for guidance of intervention after failed thrombolysis. The I.S.A.M. study included 1,741 patients with acute myocardial infarction of less than 6 hours duration being given either streptokinase or placebo. Serial blood samples for measurement of cardiac enzymes were drawn within the first 50 hours. In the streptokinase group the time to peak concentration of CK-MB activity was significantly lower (mean 10.9 hours vs 16.1 hours following initiation of treatment) as was the area under the CK-MB curve indicating reduction of infarct size (Table 2). A substudy investigating the myoglobin release in 120 patients having received streptokinase or placebo demonstrated higher maximum values in the streptokinase group (mean 3008 vs 2097 ng/ml), a shorter time to peak interval following treatment (3.4 vs 6.5 hours) and a reduction in infarct size as suggested by a smaller area under the myoglobin curve (17,377 vs 23,240 ng/ml x h) (Table 3). For LDH/alpha-HBDH the reduction in time to peak intervals was less impressive (Table 4). In angiographic studies with TIMI flow 3 at 90 minutes in the infarct related artery in 22 patients (Figure 5) the maximum myoglobin value was reached in less than 4.2 hours (mean value plus SEM) following treatment (9.5 hours for CK-MB activity). Therefore, myoglobin seems to be the preferred marker in reperfusion assessment.     

Planar myocardial scintigraphy with 99mTc sestamibi for the evaluation of the infarct area and the efficacy of the thrombolytic therapy]

BACKGROUND: Nuclear cardiology permits the estimation of myocardial infarction size and the result of the thrombolytic therapy. The aim of the study was to demonstrate the feasibility of the planar myocardial scintigraphy with tecnetium-99m-sestamibi in the coronary intensive care unit for the early identification of the infarct size and the results of the thrombolytic therapy. MATERIAL AND METHODS: We studied 15 patients affected by a first acute myocardial infarction (AMI), 10 anterior and 5 inferior wall, treated with thrombolysis (APSAC 30U i.v.) within and interval of 3 hours from the symptoms onset, tecnetium-99m-sestamibi was injected before thrombolysis and after 3 +/- 1 hours the planar imaging was registered with a mobile gamma-camera. Scintigraphic evaluation was repeated after 24 hours and before patient discharge. Within 48 hours from the thrombolytic therapy the coronary angiography was performed for the demonstration of patency of the infarct-related artery. The left ventricle myocardial perfusion was divided in the 3 planar projections into 13 segments. The perfusion in each segment was evaluated with a perfusion score: 0 = normal, 1 = moderately reduced, 2 = severely reduced, 3 = absent. The sum of the hypoperfused segments represented the infarct size. A perfusion score improvement greater than 40% was considered a marker of reperfusion. RESULTS: The infarct size involved 4.2 +/- 1.5 segments in the anterior and 2 +/- 0.8 segments in the inferior wall infarctions (p < 0.05). The scintigraphic imaging made 24 hours after AMI allowed the diagnosis of coronary reperfusion in 10 patients. The coronarography demonstrated the infarct related artery patency in 14 patients. The nuclear imaging at patient discharge provided the diagnosis or reperfusion in 11 cases and demonstrated an improvement of the myocardial perfusion score in 8 cases. CONCLUSIONS: In patients with AMI treated with thrombolysis the scintigraphic imaging with tecnetium-99m-sestamibi is feasible with a mobile gamma-camera in the intensive coronary care unit. The quality of planar imaging is good and allows the evaluation of myocardial infarct size and the efficiency of thrombolytic therapy. An earlier scintigraphic imaging should be taken into consideration for a more timely non-invasive evaluation of patients who need coronary angiography and, if necessary, a rescue-PTCA.     

Value of immediate coronary angioplasty following intracoronary thrombolysis in acute myocardial infarction

A total of 533 patients with acute myocardial infarction of less than 4-h duration were enrolled in the multicenter randomized trial of intracoronary thrombolysis compared to conventional treatment. In two of the five participating centers, an additional coronary angioplasty immediately after thrombolysis was attempted in 46 patients. According to the treatment allocation and early and late patency of the infarct related vessel, patients were subdivided into three groups: conventionally treated (group A); successful coronary angioplasty following thrombolysis with persistent patent infarct related vessel (group B); and late patency of the infarct related vessel postthrombolytic therapy without angioplasty (group C). The highest global ejection fractions were observed in group B (54% +/- 10%) and group C (55% +/- 13%), while the lowest ejection fraction was found in group A (47% +/- 14%). The sequential changes in global ejection fraction from the acute to the chronic stage was + 4% (p = 0.05) in group B, while no significant changes could be demonstrated in group C. Furthermore, in the group successfully treated by angioplasty, the improvement in global ejection fraction was more pronounced and persisted up to three months after the intervention. This was supported by analysis of regional myocardial function of the infarct zone (+ 16% improvement, p = 0.01). The long-term clinical follow-up (median 24 months) of the patients successfully treated by combined procedure of thrombolysis and angioplasty (group B) was most favourable with a lower incidence of re-infarction (6%), and late coronary bypass surgery (13%) and/or (re)-percutaneous transluminal coronary angioplasty (3%) was performed less frequently. These results suggest that reperfusion may need to be supplemented by additional revascularization procedures in order to optimize the changes of obtaining full functional recovery and so to improve the prognosis.     

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.     

Correlation of baseline plasminogen activator inhibitor activity with patency of the infarct artery after thrombolytic therapy in acute myocardial infarction

Increased levels of plasminogen activator inhibitor (PAI) have recently been described in patients with acute myocardial infarction (AMI). To correlate PAI levels to patency of infarct arteries after thrombolytic therapy with recombinant tissue-type plasminogen activator (rt-PA), 125 consecutive patients with AMI were examined. Blood levels of fibrinogen, plasminogen, tissue plasminogen activator (t-PA) and PAI were measured before treatment initiation, 10 minutes after completion of rt-PA infusion and 24 and 48 hours after treatment. Coronary angiography, performed in all patients 72 hours after beginning rt-PA infusion, revealed patent infarct arteries in 97 patients and occluded infarct arteries in 28 patients. Pretreatment levels of PAI were significantly higher in patients with occluded infarct arteries (18.0 +/- 11.5 vs 10.5 +/- 9.3 IU/ml, p less than 0.01). Conceivably, higher levels of PAI may interfere with the natural thrombolytic process and make pharmacologic thrombolytic intervention less effective.     

Impact of spontaneous anterograde flow of the infarct artery on left ventricular function in patients with a first anterior wall acute myocardial infarction

To assess the impact of spontaneous anterograde flow of the infarct artery on outcomes in patients with acute myocardial infarction (AMI), we studied 478 patients with a first anterior wall AMI who underwent coronary angiography within 12 hours after the onset of chest pain; Thrombolysis In Myocardial Infarction (TIMI) 3 flow was obtained after reperfusion therapy. Patients were divided into 3 groups: 119 patients with spontaneous anterograde flow (initial TIMI 2 or 3 flow) of the infarct artery, 118 patients with an initially occluded artery (TIMI 0 or 1 flow) and time to angiography or=55% (odds ratio 7.13, 95% confidence interval 3.10 to 16.4, p <0.001). In conclusion, although very early reperfusion improved LV function more than late reperfusion, spontaneous anterograde flow was associated with better acute and predischarge LV function after AMI compared with very early reperfusion of an initially occluded artery.     

Reduction in ST segment elevation after thrombolysis predicts either coronary reperfusion or preservation of left ventricular function

The usefulness of a reduction in ST segment elevation to predict coronary reperfusion in myocardial infarction remains uncertain. ST segment changes and angiographic findings were compared in 45 patients soon after thrombolysis. The percentage ST segment change 3 hours after treatment (in the lead showing the greatest initial ST elevation) was compared with the TIMI perfusion grade (thrombolysis in myocardial infarction trial) obtained between 90 minutes and 3 hours after treatment. Global ejection fraction and regional wall motion were assessed by cineventriculography (11 (5) days (mean (SD))) and by gated blood pool imaging (44 (11) days). Prediction of coronary patency by a reduction of greater than 25% in ST segment elevation 3 hours after thrombolytic treatment had a sensitivity of 97% but a specificity of only 43%. Where the ST segment elevation was reduced by greater than 25% the global ejection fraction was well maintained whether or not the infarct vessel was patent. In patients with a reduction of less than 25% in ST elevation, the ejection fraction was significantly lower and regional wall motion abnormality more severe. Reduction in ST elevation of greater than 25% within 3 hours of thrombolysis indicates either a patent infarct artery or preservation of left ventricular function. When the ST segment elevation does not fall by greater than 25% persistent coronary occlusion is likely (predictive accuracy 86%) and is associated with a lower ejection fraction. These patients may benefit from further treatment or additional interventions.