Effect Of Thrombolytic Therapy Research Articles

Effects of early thrombolytic therapy (anistreplase versus streptokinase) on enzymatic and electrocardiographic infarct size in acute myocardial infarction

The effects of thrombolytic therapy on enzymatic and electrocardiographic indexes of myocardial infarction were examined in 370 patients who were enrolled within 4 hours of onset of symptoms and were randomized to blinded therapy with intravenous anistreplase (30 U/5 min, n = 188) or Streptokinase (1.5 million IU/1 hour, n = 182). Creatine kinase and its MB isoenzyme were initially measured every 4 to 6 hours, and lactic dehydrogenase (LDH) and its cardiac isoenzyme (LDH-1) every 8 to 12 hours. Electrocardiograms were obtained before, and at 90 minutes and 8 hours after starting thrombolysis, and on discharge. Enzymatic and etectrocardiographic measures of infarction were compared between drug treatment and patency groups. Early patency was associated with significant reductions in peak values for each of 4 cardiac enzymes (averaging 21 to 25%, p < 0.01 to 0.001), even though later rescue procedures were often used in the nonpatent group; times to peaks were also reduced for 3 of the enzymes. Treatment with anistreplase was associated with enzymatic peaks that tended to be lower than with streptokinase (6 to 16%), approaching or reaching significance for LDH (p ≤ 0.07) and LDH-1 (p ≤ 0.04); times to peaks were similar. Early patency favorably affected electrocardiographic indexes. Summed ST-segment elevations resolved more rapidly (p ≤ 0.04), summed Q-wave amplitude was reduced by 32% (p ≤ 0.01), and total QRS infarct score on discharge was 22% less (p ≤ 0.006) in those achieving early patency. Small differences in electrocardiographic indexes between the 2 drug treatment groups were not significant. These results support use of early reperfusion to reduce infarct size in acute myocardial infarction with administration of streptokinase and anistreplase.

Did prognosis after acute myocardial infarction change during the past 30 years? A meta-analysis

Much effort has been spent to improve survival after acute myocardial infarction. To investigate how effective this effort has been, a meta-analysis was performed of studies published between 1960 and 1987 concerning mortality after acute myocardial infarction. Thirty-six studies were analyzed. They were classified with respect to deaths in the hospital and at 1 month and the 5-year mortality rate starting at hospital discharge.Mortality was assessed from all studies by comparing studies from different institutions with use of identical inclusion criteria (externally controlled studies) and by analyzing studies reporting on changes in mortality in two or more comparable patient cohorts admitted to the same institution at different time periods (internally controlled studies). Reports on clinical trials (for example, thrombolytic therapy, beta-adrenergic blockade) in acute myocardial infarction were excluded.Average overall in-hospital mortality decreased from 29% during the 1960s to 21% during the 1970s and to 16% during the 1980s. The externally controlled studies also showed a declining trend: from 1960 to 1969, 32%, from 1970 to 1979, 19% and from 1980 to 1987, 15%. The 1-month overall mortality rate decreased from 31% during the 1960s to 25% during the 1970s and 18% during the 1980s externally controlled studies. Most internally controlled studies also showed significant improvement in inhospital and 1-month survival. In contrast, 5-year mortality after hospital discharge did not significantly decrease (33% from 1960 to 1969 and 33% from 1970 to 1979).It is concluded that in the prethrombolytic era, short-term prognosis after acute myocardial infarction has improved since 1960. Changes in long-term prognosis after hospital discharge, however, could not be demonstrated. Information about the effect of thrombolytic therapy and early revascularizalion is urgently needed.

Dry reagent technology for rapid, convenient measurements of blood coagulation and fibrinolysis

Rapid coagulation and fibrinolysis assays suitable for use with an imprecisely measured sample volume (either whole blood or plasma) have been developed, utilizing a technology based on paramagnetic iron oxide particles (PIOP) that move in response to an oscillating magnetic field. PIOP are combined with appropriate test reagents for clotting and thrombolysis assays and formulated as dry reagents within a capillary test chamber. The minima and maxima of the PIOP oscillations define a two-sided waveform that provides kinetic information on fibrin polymerization and lysis. Subject to the chemistry of the dry reagent formulation, the resulting waveform can be used to define clotting time, lysis onset time, or fibrinogen variables. Applications to one-stage prothrombin time and one-stage activated partial thromboplastin time tests have yielded assays with consistently good correlations with other test methods. Applications to fibrinolysis studies have yielded global assays of thrombolytic activity, in that the assay results reflect the interactions of multiple factors associated with the effectiveness of thrombolytic therapy. Depending on the components utilized in a particular reagent formulation, one can derive information about the activity of such factors as fibrinogen, plasminogen, and related inhibitors, as well as the lytic agent being administered. Use of these assays in a clinical setting should provide a rapid, convenient alternative to conventional testing of coagulation variables and a reliable method for monitoring thrombolytic therapy.

Pericardial effusion after intravenous recombinant tissue-type plasminogen activator for acute myocardial infarction

The effect of thrombolytic therapy on the frequency, time course and sequelae of pericardial effusion after myocardial infarction are unknown. A prospective, serial, 2-dimensional echocardiographic study of patients with myocardial infarction who received recombinant tissue-type plasminogen activator (rt-PA) was undertaken to address this issue. The study population comprised 52 of the 112 patients enrolled in the first Thrombolysis and Angioplasty in Myocardial Infarction trial at Duke University Medical Center. Enrollment in the serial echocardiography protocol was determined by equipment and support staff availability. Complete echocardiographic studies were performed within 90 minutes after initiation of thrombolytic therapy (day 0), and on days 1, 3 and 6. Patients undergoing serial echocardiography did not differ in demographic or clinical characteristics from those who did not. Pericardial effusion was present in 3 of 38 patients (8%) at day 0, in 2 of 44 (5%) at day 1, in 8 of 43 (19%) at day 3, and in 10 of 42 (24%) at day 6. By day 6,3 of 10 pericardial effusions were moderate in size, 1 of 10 was large and the remainder were small. No patients developed echocardiographic or hemodynamic signs of cardiac tamponade. The prevalence and time course of pericardial effusion among patients with acute myocardial infarction who received rt-PA in this study are similar to observations reported in earlier studies in which patients did not receive thrombolytic therapy. Adverse sequelae of pericardial effusion after thrombolytic therapy are rare.

The Varying Effects of Thrombolytic Therapy in Unstable Angina

The Varying Effects of Thrombolytic Therapy in Unstable Angina

Unstable angina: current concepts of medical management.

Unstable angina describes a clinical syndrome bridging the gap between stable angina and acute myocardial infarction. By definition, patients with angina of new onset, of a crescendo pattern, and with angina at rest are included in this high-risk group. The underlying pathogenetic mechanisms are complex and include initial atherosclerotic plaque rupture, release of vasoactive substances, and intracoronary thrombus formation. The currently established medical approach of the acute phase consists of heparin for anticoagulation and nitrates combined with beta-blockers for the relief of pain. Calcium antagonists are indicated, if anginal symptoms persist. The effect of thrombolytic therapy is still under investigation. Angina refractory to medical treatment and angina at rest are associated with a particularly unfavorable prognosis and prompt early catheterization. The long-term prognosis of the patient is markedly improved by chronic platelet inhibitory treatment with aspirin.

Effects of thrombolytic therapy in unstable angina: Clinical and angiographic results

The incidence of intracoronary thrombus and the effects of thrombolytic therapy were studied in 41 patients with unstable angina. All patients underwent coronary angiography 2 to 69 h (mean 19) after their last attack of chest pain. Immediately after angiography, 21 patients received intracoronary streptokinase (250,000 IU in 45 min) and were retrospectively analyzed. Twenty patients received intravenous recombinant tissue-type plasminogen activator (rt-PA) (100 mg in 3 h) and were involved in a prospective study.Eleven of the 21 patients from the streptokinase group and 11 of the 20 patients from the rt-PA group showed a decrease in the severity of the coronary stenosis on repeat angiography 1 day later. A decrease in coronary obstruction was primarily observed in 10 of 13 patient; with a complete stenosis and in 6 of 9 patients with a subtotal stenosis and markedly diminished coronary flow. Improvement in coronary anatomy was not determined by the clinical characteristics of the patients. Twenty-eight of the 41 patients had angiographic evidence of intracoronary thrombus formation before and 16 had such evidence after thrombolytic treatment. Nine patients developed a small increase in serum cardiac enzymes before or during treatment. Ischemic symptoms and the incidence of surgical or angioplastic intervention were not different in patients with or without a reduction in coronary artery stenosis after fibrinolytic therapy.These observations suggest a high incidence of coronary thrombosis in patients with unstable angina. The data do not permit assessment of the clinical therapeutic efficacy of thrombolylic therapy. Better risk stratification and placebo-controlled prospective studies are required to obtain information on the risk/benefit ratio of such therapy in unstable angina.

Echocardiography in Coronary Artery Disease

1. Direct ultrasonic visualization of the coronary arteries.- 2. Regional and global left ventricular function analysis.- 3. Echocardiography during reversible ischemia in animal models.- 4. Echo-doppler cardiography during percutaneous transluminal coronary angioplasty.- 5. Exercise echocardiography.- 6. Dipyridamole-echocardiography test.- 7. Echocardiography in experimental myocardial infarction in animals.- 8. Myocardial perfusion imaging by contrast two-dimensional echocardiography.- 9. Echocardiography in the differential diagnosis of patients with chest pain.- 10. Acute myocardial infarction in man.- 11. Evaluation of the effect of thrombolytic therapy on left and right ventricular function by two-dimensional echocardiography and cineventriculography.- 12. The mechanical complications of acute myocardial infarction.- 13. Left ventricular aneurysm and infarct expansion.- 14. Left ventricular thrombus: diagnosis, anticoagulation, and systemic embolization.- 15. Doppler echocardiography in coronary artery disease.- 16. Epicardial echocardiography: assessment of myocardial effects of ischemia and revascularization.- 17. Transesophageal echocardiography during abdominal aortic surgery.- 18. Ultrasonic tissue characterization methods in the diagnosis of coronary artery disease.- 19. Direct epicardial visualization of the coronary arteries.

Effects of Thrombolytic Therapy on Hemorrhage from Post-operative Wounds

SummaryHemorrhage from post-operative wounds in different organs and structures during thrombolytic therapy was investigated in relation to the time after surgical trauma and to the results of laboratory tests of coagulation and fibrinolysis. Streptokinase was given to rabbits at different times following the production of standardized wounds in different organs. Bleeding was frequent and severe when streptokinase was given between one and five days after surgery and was most marked from artery, followed in order by kidney, vein, liver, muscle, gut and skin. Bleeding appeared to be associated with the in vitro demonstration of an active systemic fibrinolytic state together with elevated levels of fibrin degradation products.

Thrombolysis with Streptokinase in Rabbits Dose Response, Fibrin-clot Specificity and Laboratory Evaluation of Fibrinolytic Effect

SummaryAn animal model was used in which venous thromboemboli of reproducible size could be formed. The effects of SK 500–50,000 units per hour were evaluated and compared to those of saline. Proportionately the greatest clot lysis occurred with the lowest doses of SK. In contrast to thrombolysis, significant fibrinogenolysis did not occur in any of the animals indicating a high degree of specificity of SK-induced activator for rabbit fibrin. An excellent correlation between the concentration of fibrin degradation products (fdp) measured by the serial dilution protamine sulfate test and the extent of clot lysis was found suggesting this to be a useful method for monitoring the effects of thrombolytic therapy. A method for the laboratory distinction of fdp from fibrin monomer was demonstrated.