A systemic non-lytic state and local thrombolytic failure of anistreplase (anisoylated plasminogen streptokinase activator complex, APSAC) in acute myocardial infarction

The relation between coronary thrombolysis and coagulation variables after administration of anistreplase (anisoylated plasminogen streptokinase activator complex, APSAC) was studied in patients with an acute myocardial infarction. Fifty eight consecutive patients with acute myocardial infarction were given 30 U of anistreplase intravenously within 4 hours of the onset of symptoms. A fall in the plasma concentration fibrinogen to less than 1.0 g/l 90 minutes after administration of anistreplase was considered to reflect a systemic lytic state. Coronary angiography was performed 48 hours after thrombolytic treatment. The overall patency rate was 74% (43/58). Patency rates were significantly different in patients with a systemic lytic (83% (43/52)) and a systemic non-lytic state (0% (0/6)). The absence of a systemic lytic state after anistreplase administration seemed to be highly predictive of the failure of coronary thrombolysis. Coagulation studies showed evidence of inhibition of anistreplase induced fibrinolytic activity which may explain the failure of thrombolytic treatment in patients with evidence of a systemic non-lytic state.     

Are the various thrombolytic agents equally effective in the treatment of acute transmural myocardial infarction?

While it is no longer possible to imagine the treatment of an acute transmural myocardial infarction without the use of thrombolytic agents, some discussion still exists as to the choice of the thrombolytic agent. Our study concerns a group of 160 patients with an acute transmural myocardial infarction, 60 of whom were treated with anistreplase, 52 with streptokinase and 48 with alteplase. Statistically, the administration of anistreplase was associated with a significantly higher frequency of ventricular arrhythmias in comparison to the other thrombolytic agents, whereas after subsequent coronary angiography, the anistreplase group revealed a significantly lower number of completely occluded coronary arteries. The data from this study demonstrate that anistreplase is a very valuable thrombolytic agent. It may even be more effective than streptokinase and alteplase in the treatment of acute myocardial infarction when the patency of the coronary arteries 1 month after the acute coronary event is considered the primary endpoint.     

Relation of effectiveness of intracoronary thrombolysis in acute myocardial infarction to systemic thrombolytic state

Twenty-nine patients received intracoronary thrombolytic therapy for acute myocardial infarction 3.5 +/- 1.4 hours (mean +/- standard deviation) after the onset of pain. Ten patients received urokinase (UK) and 19 patients received streptokinase (SK). Laboratory variables of the coagulation system were measured before and immediately after therapy. When comparing patients in whom coronary artery recanalization occurred vs those in whom the artery remained occluded, those in whom recanalization was achieved had greater alterations in fibrinogen, prothrombin time, activated partial thromboplastin time, fibrin/fibrinogen degradation products and plasminogen by thrombolytic therapy than did those in whom recanalization was not achieved (p less than 0.05 for all variables). Euglobulin lysis time showed a similar but nonsignificant trend (p = 0.114). Patients who received SK showed markedly greater alterations in coagulation parameters than did patients treated with UK (p less than 0.05 for 5 of 6 variables measured) and had a much higher incidence of successful thrombolysis (74% for SK, 20% for UK). These data indicate that the development of a systemic fibrinolytic state contributes to success when using intracoronary thrombolytic agents in acute myocardial infarction. Rather than being considered an adverse effect of therapy, a systemic lytic state may serve as a reasonable clinical goal in attempting to produce thrombolysis.     

Having of mortality at 1 year by domiciliary thrombolysis in the grampian region early anistreplase trial (GREAT)

Objectives. Our aim was to determine the time saved by administration of thrombolytic therapy at home rather than in the hospital and to assess whether earlier thrombolysis resulted in decreased mortality from acate myocardial infarction.Background. There is much theoretic, experimental and trial evidence to indicate that in acute myocardial infarction the earlier that thrombolytic therapy is given, the greater its efficacy. However, the clinical importance of this time effect is uncertain.Methods. In a randomized double-blind parallel-group clinical trial, 311 patients with suspected acute myocrdial infarction seen by their general practitioners within 4 h of symptom onset were given intravenous anistreplase (30 U) either at home or later, after arrival in the hospital.Results. Anistreplase was given at home or in the hospital at median times of 101 and 240 min, respectively, after symptom onset. The median time saved by domiciliary thrombolysis was 130 min. By the end of 1 year after trial entry, 17 (10.4%) of 163 patients given anistreplase at home died compared with 32 (21.6%) of 148 in those allocated anistreplase in the hospital (relative reduction 52%, 95% confidence interval 14% to 89%, p = 0.007).Conclusions. In this trial the time saved by domiciliary thrombolysis by primary care physicians was >2 h. It is likely that a similar time saving would be achieved if prehospital thrombolysis were to become established practice. Prehospital thrombolysis resulted in a halving of the mortality rate from acute myocardial infarction.     

The therapy of acute myocardial infarction: current state of the art

For decades management of acute myocardial infarction (AMI) consisted of bed rest, oxygen, prevention for thromboembolic complications, and treatment of arrhythmias and heart failure. In the last years a more aggressive treatment of AMI has been developed, based on the following three basic principles: (1) Mortality of patients with AMI is determined by the infarct size and the degree of left ventricular dysfunction. (2) The time interval between the onset of coronary occlusion and any intervention to limit infarct size is brief and takes usually not more than three to four hours. (3) After the acute phase of infarction a lot of patients remain at high risk of fatal coronary events, i.e. reinfarctions. The angiographic findings during the first hours of AMI showed in about 80% of patients an obstructive coronary thrombus and led to efforts to dissolve the offending thrombi. The demonstration that coronary thrombi can be lysed in about 80% of cases within 60 minutes after the intracoronary injection of thrombolytic agents (streptokinase or urokinase) has boosted the reperfusion therapy in AMI in the hope that ischemic myocardium might be salvaged. Intracoronary infusion of thrombolytic agents however, can be applied only in a minority of patients with AMI because coronary angiography and a skilled team of investigators are required, therefore a short-time intravenous high dose streptokinase infusion was developed. In the meantime two large double blind randomized trials (ISAM and GISSI) could demonstrate a reduction in hospital mortality in AMI especially by early treatment with intravenous streptokinase. Conventional thrombolytic agents produce a systemic lytic state with the possibility of hemorrhage, therefore recombinant tissuetype plasminogen activator (rt-PA) and two other drugs, acylated streptokinase and pro-urokinase, were developed with the aim of inducing coronary thrombolysis without severe systemic lytic state, but the efficacy of these new drugs remains to be demonstrated in randomized trials versus conventional thrombolytic agents.(ABSTRACT TRUNCATED AT 250 WORDS)     

Unresolved issues in the thrombolytic treatment of myocardial infarction.

Despite enormous advances made in understanding of the biochemistry of fibrinolytic agents and their extensive clinical use in acute myocardial infarction a number of unresolved issues remain. There is an intriguing divergence of left ventricular response and reduction of mortality in patients with acute myocardial infarction treated with thrombolytic drugs. It is also difficult to explain why patients treated late have a reduced mortality after thrombolytic treatment. Uncertainty prevails on the validity of thrombolysis in patients with a low and very high risk of mortality. Resistance of coronary occlusion to any thrombolytic is another unexplained fact. Alteplase and saruplase are more fibrin-specific thrombolytic drugs than anistreplase. These and the thrombolytic drugs of the first generation (streptokinase and urokinase) have shortcomings and limitations. It is being explored whether prolonged intravenous maintenance infusions are more effective if replaced by a bolus injection, accelerated infusion or the combined intravenous administration of thrombolytic agents.     

Lack of influence of pretreatment antistreptokinase antibody on efficacy in a multicenter patency comparison of intravenous streptokinase and anistreplase in acute myocardial infarction.

Antistreptokinase antibodies present in patients as a result of previous streptococcal infections might theoretically influence the thrombolytic response to streptokinase or anistreplase. The potential influence of antibody, measured as antigen binding to immunoglobulin G, was investigated in a randomized, double-blind, multicenter patency comparison of intravenous streptokinase (1.5 million units/60 minutes) and intravenous anistreplase (30 units/2 to 5 minutes) in patients with acute myocardial infarction. Antibody results were evaluated in 333 patients (from a total study population of 370 patients) less than 76 years of age with ECG evidence of ST segment elevation who could be treated within 4 hours of the onset of symptoms. Variations in pretreatment circulating levels of antibody did not influence angiographically defined early coronary patency rates (Thrombolysis in Myocardial Infarction grade 2 or 3 perfusion, measured at a mean of 140 minutes after therapy was begun) for either streptokinase or anistreplase. Similarly the lytic response represented by systemic plasminogen activation and measured as changes in plasma plasminogen and fibrinogen levels after dosing (at mean times of 90 minutes and 24 hours) was not correlated with baseline antibody levels. Furthermore, pretreatment antibody was not a risk factor for poor outcome in response to streptokinase or anistreplase (reocclusion within 24 hours, in-hospital death, or stroke) and did not correlate with hypotension or allergic-type reactions recorded as adverse events. In conclusion, within the population limits defined by the inclusion and exclusion criteria of the study (patients were excluded if they had received streptokinase or anistreplase within the previous 6 months), pretreatment antistreptokinase immunoglobulin G is not a significant determinant of the efficacy response to streptokinase or anistreplase.     

Thrombolytic therapy of acute myocardial infarction

Thrombotic coronary artery occlusion is now recognized as the usual cause of acute myocardial infarction. The thrombus usually forms at the site of intimal disruption over an atherosclerotic plaque. Following coronary occlusion, myocardial necrosis begins within 40 minutes in the subendocardium and progresses outward toward the epicardium over the next several hours. The intracoronary infusion of streptokinase will produce lysis of the occluding thrombus in up to 80% of patients. It appears that reperfusion with streptokinase in the first few hours following the onset of the myocardial infarction produces a small increase in late left ventricular function, though ECG and enzyme evidence of acute myocardial infarction are not prevented. The improvement in left ventricular function is variable from patient to patient and has not been demonstrated in all the randomized studies to date. The time limit for myocardial salvage may not be the same in all patients. The greatest benefit is probably achieved with reperfusion in the first 4-6 hours, although some benefit may occur as late as 18 hours after the onset of infarction. Many patients who receive intracoronary infusion of streptokinase develop a systemic lytic state, though serious bleeding complications in carefully selected patients are infrequent. High-dose IV streptokinase is easier, cheaper, and quicker to initiate than intracoronary streptokinase but is probably less effective than the intracoronary route in producing rapid lysis of the occluding coronary thrombus. The optimal dose and rate of administration of IV streptokinase have not been determined. The final role and ultimate benefit of thrombolytic therapy of myocardial infarction have not yet been determined, but some of the issues may be clarified by the larger randomized trials now under way. It appears, at present, that the use of intracoronary streptokinase may have a role in the treatment of selected patients with acute myocardial infarctions in institutions with the facilities and the personnel necessary to perform this procedure safely. In the future, thrombolytic therapy may also have a place in the treatment of selected patients with unstable angina and post-myocardial infarction angina. The future availability of more selective thrombolytic agents may make the early IV therapy of myocardial infarction a safer, more effective option and expand the indications for thrombolytic therapy.     

Efficacy of coronary angioplasty following conventional coronary thrombolysis in patients with acute myocardial infarction

The efficacy of combined thrombolysis and angioplasty for the purpose of coronary reperfusion after acute myocardial infarction has been controversial. The present study was conducted, therefore, to evaluate the effects of angioplasty following administration of conventional thrombolytic agents on the long-term prognosis of acute myocardial infarction patients. A total of 409 patients admitted to the hospital within 12 hours of the onset of infarction between January 1990 and May 2001 were studied retrospectively. These included 151 patients treated with thrombolysis alone (group T), 73 patients treated with angioplasty alone (group A), and 35 patients treated with angioplasty after thrombolysis (group T&A). Group T&A had shorter intervals from onset to initial treatment than group A (3.0 hours vs 6.3 hours, p < 0.01), a higher reperfusion success rate than group T (91.4% vs 74.8%, p < 0.01), and more improved left ventricular wall motion than group A. One-year cardiac mortality rates tended to be higher in group T, which had a higher rate of unsuccessful reperfusion than groups T&A or A (8.1% vs 3.4% vs 3.5%). The frequencies of hemorrhagic complications were similar among the 3 groups. From these findings, we conclude that thrombolytic therapy with subsequent angioplasty is an effective strategy for achieving cardiac reperfusion following acute myocardial infarction.     

Comparison of intravenous anisoylated plasminogen streptokinase activator complex and intracoronary streptokinase in acute myocardial infarction

Coronary angiography was used to compare the efficacy of anisoylated plasminogen streptokinase activator complex (APSAC) administered intravenously and streptokinase given by intracoronary infusion in inducing reperfusion in patients with a proven acute myocardial infarction. Forty-two patients received 30 U of APSAC intravenously over 5 minutes and 43 patients received 250,000 IU of streptokinase given via intracoronary infusion over 90 minutes, after occlusion of the infarct-related vessel was demonstrated by angiography. Reperfusion was achieved in 23 (64%) of 36 patients (mean time to reperfusion 46 minutes) treated with APSAC and 25 (67%) of 37 patients (mean time to reperfusion 45 minutes) treated with intracoronary streptokinase, who were angiographically evaluated 90 minutes after the start of treatment. Twenty-four hours after treatment, reocclusion had occurred in 1 (5%) of 22 patients in the APSAC group and in 3 (13%) of 23 patients in the streptokinase group. No major bleeding was observed in either treatment group despite a similar systemic lytic state that lasted for up to 48 hours. Two patients treated with APSAC died after severe left ventricular failure unrelated to therapy. The results indicate that APSAC given intravenously is as effective as streptokinase given intracoronary in producing thrombolysis in acute myocardial infarction. The major advantages of APSAC are its rapid and convenient administration by a single intravenous injection, the low rate of arterial reocclusion and good patient tolerance.     

Changes in mortality of acute myocardial infarction as a function of a changing treatment during the last two decades

Forty years ago, after the establishment of coronary care units, a significant decrease in mortality of acute myocardial infarction was noted. Twenty years ago, the break-through of thrombolysis realized once again a significant decrease in mortality. In this study we compare, in a rather small community hospital, the mortality and safety of thrombolytic therapy in acute myocardial infarction with a more conventional, conservative medical therapy. We examined all cases of acute myocardial infarction between 1978 up to 1998 inclusive, concerning treatment and mortality rate after a six month period. To be included in the study, acute myocardial infarction had to fulfill particular inclusion criteria. A total of 1863 cases of acute myocardial infarction were included. The mortality rate of patients with acute myocardial infarction treated with thrombolytic agents was strikingly lower and statistically very significantly different (p < 0.001) in comparison with the mortality rate of patients treated with heparin or coumarine derivatives. The mortality rate dropped from 10.57% in the coumarine group and from 14.95% in the heparin group to 5.41% in the alteplase group, to 4.95% in the anistreplase group and 4.00% in the streptokinase subgroup. The complications directly connected to the treatment did not seem to be different between the five groups, and they were also not more frequent by using thrombolytic agents. In the last 20 years, better preventive measures (life habits, diet, medication) and trials to better control the risk factors have not influenced greatly the average amount of cholesterol in patients with an acute myocardial infarction. Also the percentage of patients with high blood pressure has hardly decreased over the last 20 years. The mortality associated with acute myocardial infarction has decreased significantly with the use of thrombolytics. In most cases, thrombolytics are administered routinely and safely. In this way, they are the first choice therapy for myocardial infarction in smaller hospitals. To obtain excellent coronary patency, thrombolytic agents with a long half-life and with PAI-1 resistance are required in the future. The current measures and medical therapies seem to be insufficient to control the risk factors for coronary atherosclerosis.     

Thrombolysis in acute myocardial infarction complicated by cardiogenic shock

The adverse impact of the development of cardiogenic shock in the setting of acute myocardial infarction was first described by Killip and Kimball in 1967. While the inhospital mortality rate in patients with myocardial infarction and no evidence of heart failure was only 6%, the mortality rate in those patients who developed cardiogenic shock was 81%. Despite advances in cardiovascular care and therapy since that initial report, including universal institution of cardiac care units, advances in hemodynamic monitoring, new inotropic and vasodilating agents, and even increasing utilization of thrornbolytic therapy, the mortality from acute myocardial infarction, when complicated by cardiogenic shock, remains disturbingly high, and cardiogenic shock remains the leading cause of death of hospitalized patients following acute myocardial infarction.The grave prognosis associated with this condition has resulted in increased interest in potential therapeutic interventions, particularly in the area of reperfusion therapy. Several studies suggest that, in contrast to the beneficial effects of thrombolytic therapy in most patient populations suffering acute myocardial infarction, mortality rates are not decreased in those patients with cardiogenic shock at the time of lytic administration. Thrombolytic administration does, however, appear to lead to a modest reduction in the percent of patients with myocardial infarction who will subsequently develop cardiogenic shock during hospitalization.Reperfusion rates with lytic therapy in patients with cardiogenic shock are disappointingly low, in the range of 42–48%, significantly lower than those achieved in patients without cardiogenic shock. These low perfusion rates may, in part, be explained by decreased coronary blood flow and perfusion pressure in patients with left ventricular pump failure.Although promising as adjunctive therapy, it is unclear whether institution of balloon counterpulsation has any long-term benefit in patients with cardiogenic shock treated with thrombolytic therapy. Whether other or additional interventions, such as coronary angioplasty and coronary artery bypass graft (CABG), decrease mortality rates in patients with cardiogenic shock remains to be determined.     

Delayed thrombolytic treatment of older patients with acute myocardial infarction.

OBJECTIVE: To determine demographic and clinical factors associated with delayed thrombolysis in patients with acute myocardial infarction. DESIGN: A retrospective cohort. SETTING: 37 Minnesota hospitals during the time periods October 1992-July 1993 and July 1995-April 1996. PATIENTS: We reviewed the medical records of 776 older patients aged 65 or older hospitalized with an admission diagnosis of acute myocardial infarction, suspected acute myocardial infarction, or rule-out acute myocardial infarction, who were treated with a thrombolytic agent. MEASUREMENT: We used multivariate logistic regression models to examine the association between selected study characteristics and time between hospital presentation and administration of thrombolytic treatment. Early thrombolysis was defined as less than 60 minutes after hospital presentation and late thrombolysis as 60+ minutes. RESULTS: Of 776 study patients, 57.5% (n = 446) received early thrombolysis. Of the remaining 330 patients receiving late treatment, 12.1% (n = 94) were thrombolyzed more than 2 hours after hospital presentation. After controlling for other factors, the odds of delayed thrombolysis among patients aged 75 or older were 1.48 compared with younger individuals (95% CI, 1.17-1.88). The odds of delayed thrombolysis among patients with severe comorbidity were 1.46 (95% CI, 1.10-1.94) compared with individuals without severe comorbidity. Predictors of early thrombolytic treatment included hospital arrival via emergency transport (ORdelay = 0.46; 95% CI, 0.34-0.63) and chest discomfort at admission (ORdelay = 0.40; 95% CI, 0.18-0.86). CONCLUSIONS: The present study indicates that patients of advanced age and with severe comorbidity are more likely to experience delayed thrombolytic treatment after hospital presentation. These are the patients who suffer the highest morbidity from acute myocardial infarction and for whom expeditious treatment may enhance therapeutic benefit.     

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.     

Role of nitrates in acute myocardial infarction

Management of patients after myocardial infarction includes several therapeutic options. Lysis of the coronary thrombosis with intravenous or intracoronary administration of streptokinase or intravenous administration of one of the newer, currently experimental agents, such as tissue plasminogen activation or prourokinase, can directly restore oxygen and substrate delivery to potentially salvageable myocardium. Percutaneous transluminal coronary angioplasty can likewise restore vessel patency with potential salvage of ischemic myocardium, if perfused sufficiently early after symptom onset. Another strategy is to administer intravenous thrombolytic therapy and then perform early angioplasty on patients with acute myocardial infarction who reach the hospital within 4 hours of symptom onset. These patients should have intravenous nitroglycerin begun before or simultaneously with beginning thrombolytic therapy. The infusion is titrated to lower systolic arterial pressure by 10% to 15%, and then maintained at a constant rate for up to 48 hours. Patients seen more than 4 hours after symptom onset, with evidence of viable myocardium (e.g., persistent R waves in those electrocardiographic leads demonstrating ST-segment elevation) may also receive intravenous nitroglycerin and thrombolytic or percutaneous transluminal coronary angioplasty therapy. The combined results of the several clinical trials of intravenous nitroglycerin in acute myocardial infarction would support its use in patients seen 4 to 12 hours after onset of symptoms or in patients seen earlier, in whom thrombolytic or percutaneous transluminal coronary angioplasty therapy cannot be utilized.     

Histidine-rich glycoprotein in thrombolytic therapy: has it clinical relevance?

The plasma concentrations of histidine-rich glycoprotein and plasminogen were measured and those of free plasminogen calculated in 34 patients with acute myocardial infarction treated with thrombolytic drugs. We investigated whether the plasma levels of histidine-rich glycoprotein and free plasminogen were associated with clinical parameters such as the occurrence and time of successful reperfusion, the incidence of reocclusion and the presence and extent of the systemic lytic state. The mean (+/- SD) pretreatment concentration of histidine-rich glycoprotein was 1.08 +/- 0.24 U/ml, which was almost identical with the normal reference values. After thrombolysis, the mean level decreased slightly. We found no support for a role of these proteins in achieving therapeutic success and only a faint suggestion that histidine-rich glycoprotein might contribute to reocclusion. Surprisingly, the non- or only limited occurrence of systemic lytic state appeared to be associated with a low level of histidine-rich glycoprotein, instead of the high level expected on theoretical grounds. It is therefore unlikely that histidine-rich glycoprotein is of clinical relevance for thrombolytic therapy of acute myocardial infarction.     

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.     

Effect of the collateral circulation on myocardial salvage in patients with acute myocardial infarction]

The effects of the extent of coronary collateral circulations, the duration of myocardial ischemia and recanalization of infarct-related vessels on left ventricular function were evaluated in 43 patients with acute anteroseptal myocardial infarction. All patients had complete occlusions of their proximal left anterior descending coronary arteries and were treated with intra-coronary thrombolytic therapy within 8 hours after the onset of their chest pain. The 43 patients were categorized in 4 groups based on the extent of their coronary collaterals in the early period of myocardial infarction and the results of thrombolysis. Group A consisted of 11 patients with well-developed collaterals who had successful thrombolysis. Group B was comprised of 14 patients with poorly developed or no collaterals, and successful thrombolysis. In group C, there were 9 patients with well-developed collaterals and unsuccessful thrombolysis. In group D, there were 9 patients who had poorly or not developed collaterals, and all had unsuccessful thrombolysis. Four weeks after the intervention, ejection fraction (EF) and regional wall motion (RWM) were calculated from the data of the left ventricular angiograms. There was no significant difference in patients' age, sex, nor in peak serum creatine kinase among the 4 groups or the duration of myocardial ischemia between groups A and B. Patients with successful thrombolysis (groups A and B) had significantly higher EF and preserved RWM of infarct areas compared to patients with unsuccessful thrombolysis (groups C and D, p less than 0.05). Thirteen patients with early reperfusion (within 4 hours after the onset of chest pain) had significantly higher EF and better RWM than did 12 patients with late reperfusion and 18 patients with unsuccessful thrombolysis (p less than 0.01). However, there was no significant correlation between the duration of myocardial ischemia and RWM of the infarct areas among 25 patients who had successful thrombolysis (r = -0.3, NS). Patients in group A had higher EF and better RWM of infarct areas than did patients in groups B, C and D (p less than 0.01). In addition, 3 patients with well-developed collaterals had good RWM despite late reperfusion which occurred more than 4 hours after the onset of symptoms. These results suggest that the extent of coronary collaterals during the early period of myocardial infarction and the time delay from the onset of symptoms to the initiation of thrombolytic therapy are important factors for the salvage of left ventricular function in patients with myocardial infarction.     

Overview of patency as an end point of thrombolytic therapy.

Underlying the use of thrombolytic therapy is the hypothesis that reestablishment and maintenance of coronary blood flow (coronary patency) are the primary mechanisms of therapeutic benefit in patients with acute myocardial infarction. Early achievement and maintenance of adequate coronary blood flow (patency) in the infarct-related artery are the primary goals of thrombolytic therapy. One third of patients may achieve spontaneous patency within a few days following acute myocardial infarction. When antithrombotic therapy (i.e., heparin) is administered, this rate increases to greater than 50%, but patency is achieved only gradually and mortality reductions comparable to thrombolytic therapy are not achieved. After administration of a thrombolytic agent, early (90-minute) patency rates are greater with alteplase or anistreplase than with streptokinase. However, patency rates for alteplase decline by 10-30% if intravenous heparin is not given concurrently. When patency is assessed greater than 24 hours following thrombolytic therapy, no significant difference exists among the agents. A single angiographic observation of the artery at 90 minutes, although useful, may be inadequate to distinguish among the beneficial clinical effects of different thrombolytic regimens. The overall reperfusion or patency profile is probably a better basis for assessing relative benefits. Intravenous thrombolytic regimens that are increasingly effective in rapidly achieving and maintaining coronary patency are now available and in further development.     

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.