Search

Background: Many antiangiogenic molecules are proteolytically cleaved from larger plasma proteins. For example, plasminogen activators cleave plasminogen into plasmin, and plasmin is converted into angiostatin in the presence of sulfhydryl donors. We thus investigated whether the antiangiogenic activity in plasma could be increased by treatment with recombinant tissue plasminogen activator (rt-PA) and the sulfhydryl donor captopril. Methods: Human plasma was treated with rt-PA (10 [micro]g/mL) and/or captopril (1 [micro]M). Angiogenesis was measured in vitro by human endothelial cell tube formation and endothelial cell proliferation and in vivo in mice with the Matrigel plug assay. Angiostatin was removed from treated plasma by affinity chromatography, immunoprecipitation, or ion-exchange chromatography, and the antiangiogenic activity of the depleted plasma was assessed by tube formation. Three cancer patients were treated with rt-PA and captopril, and their pretreatment and post-treatment plasmas were tested for antiangiogenic activity in vitro. Results: Angiogenesis in vitro was stimulated by untreated plasma and inhibited by plasma that had been treated with rt-PA and captopril but was not affected by treatment with rt-PA and/or captopril alone. In vivo angiogenesis in Matrigel plugs was substantially lower in mice treated with rt-PA and captopril than in untreated control mice. Antiangiogenic activity in treated plasma was largely retained after angiostatin was removed: treated plasma inhibited angiogenesis by 64.3% (95% confidence interval [CI] = 46.4% to 82.2%), relative to untreated plasma, and treated plasma depleted of angiostatin by affinity chromatography or immunoprecipitation inhibited angiogenesis by 65.1% (95% CI = 53.8% to 76.4%) or 63.7% (95% CI = 50.9% to 76.5%), respectively. Antiangiogenic activity of plasma from three cancer patients was higher after treatment with rt-PA and captopril than before such treatment. Conclusion: Treatment with rt-PA and captopril induced antiangiogenic activity in vitro and in vivo that appears to be independent of angiostatin. [J Natl Cancer Inst 2003;95: 388-99]

Each year, approximately 1.5 million Americans suffer a myocardial infarction (MI); nearly 500,000 of them die as a result. Most of these deaths occur soon after symptom onset and well [...]

(Chest 1995; 107:225-32) EMERAS = Estudio Multicentrico Estreptoquinasa Republicas de America del Sur; AMI = acute myocardial infarction; APSAC = anisoylated plasminogen streptokinase activated complex; GISSI-2 = Gruppo Italiano PerLo [...]

Three thrombolytic agents have been approved by the Food and Drug Administration for the management of acute myocardiol infarction: streptokinase, anistreplase, and tissue-type plasminogen activator. The best results are achieved when thrombolysis is started within 1 hour of symptom onset, but some benefit is achieved when therapy is administered within 24 hours. Routine use of these agents could result in many additional lives saved.

To ascertain whether the outcome of patients with suspected myocardial infarction differs when chest pain is still present at initiation of thrombolytic therapy, participants in the Thrombolysis in Myocardial Infarction Phase II study, all of whom presented within 4 hours of symptoms onset, were retrospectively divided into 2 groups: (1) those with chest pain present at onset of intravenous thrombolysis, n = 3,000; and (2) those who were free of chest pain on beginning intravenous thrombolytic therapy, n = 337. Patients free of chest pain were older (58 vs 57 years, p = 0.01), more often women (23 vs 17%, p = 0.01), had fewer electrocardiographic leads with ST elevation (3.8 vs 4.1, p 0.55 (35 vs 31%, p = 0.001) and fewer developed congestive heart failure (12 vs 20%). At 1-year follow-up, fewer pain-free patients developed congestive heart failure (15 vs 21%, p = 0.009), but no differences existed between the 2 groups in frequency of death, reinfarction, coronary angioplasty, bypass surgery or anginal class. Thus, there are several observations in patients who were free of chest pain at onset of lytic therapy. (1) The majority developed enzymatic or electrocardiographic evidence of acute myocardial infarction (2) Lytic therapy was safe and without excessive complications. (3) Higher ejection fraction was noted at 6 weeks, and at 1-year follow-up there was a lower incidence of congestive heart failure than among patients having pain at onset of lytic therapy. These observational data suggest that, for patients presenting within 4 hours of onset of clinical and electrocardiographic evidence of myocardial infarction, it is reasonable to administer thrombolytic therapy, even if symptoms have subsided.

Objectives: To assess differences in morbidity and mortality between men and women with acute myocardial infarction treated with thrombolytic therapy and the relation of differences to baseline patient characteristics and clinical features. Design: Secondary analysis of observational findings among women and men enrolled in a clinical trial. Setting: Hospitals participating in the Thrombolysis in Myocardial Infarction Phase II trial. Measurements: Recurrent infarctions and deaths were assessed. Main Results: The 6-week mortality rate was greater for women than for men (9% compared with 4%; adjusted relative risk, 1.54; P = 0.01). Death or reinfarction occurred in 15.9% of women and 9.5% of men (adjusted relative risk, 1.33; P= 0.02). Among patients enrolled for treatment with 100 mg of recombinant tissue plasminogen activator and assigned to a conservative strategy of watchful waiting with appropriate backup, the 6-week incidence of death was 7.5% for women and 3.8% for men (P = 0.01). The 6-week incidences of death or reinfarction were 14.2% and 8.9% (P = 0.01) among women and men, respectively. Conclusions: Among patients in the Thrombolysis in Myocardial Infarction Phase II Trial, who all were diagnosed with myocardial infarction and were eligible to receive thrombolytic therapy, women had higher rates of mortality and morbidity than did men. Older age at the time of myocardial infarction and s history of diabetes accounted for much but probably not all of this difference., Women appear more likely to die after heart attacks than men. A total of 3,339 patients with chest pain lasting 30 minutes or longer were initially treated with alteplase, a drug used to dissolve blood clots. The patients were then randomly assigned either to a routine diagnostic surgical procedure (coronary angiography) or to conventional care in which surgery was done only if indicated. Another subgroup of patients was further assigned to receive immediate beta-blocker treatment or deferred treatment. Nine percent of women and 4% of men died within six weeks of their heart attack. Death within six weeks of heart attack occurred in 11.7% of the women with additional complicating factors such as diabetes and in 5.4% of the men with additional complicating factors. Almost 16% of the women and 9.5% of the men experienced another heart attack followed by death. Women considered to have few complicating factors were 59% more likely than men with few complicating factors to have a heart attack followed by death within six weeks of chest pain.

We employed a canine model of coronary thrombosis, induced by injection of radioactive blood clot, via a catheter placed in the left anterior descending coronary artery, to compare effects of [...]

Thehe hypothesis that an infusion of recombinant tissue-type plasminogen activator (rt-PA) maintained for up to 24 hours could prevent reocclusion after early coronary patency had been established was evaluated in patients with acute myocardial infarction. The rt-PA studied was an investigation double chain rt-PA (Duteplase(R), Burroughs Wellcome Co.), administered according to body weight. Coronary patency was documented in 139 of 213 patients who had 90-minute angiograms recorded after an initial lytic dose of rt-PA. In these responders a further 90-minute infusion at one third the initial lytic dose was given before assignment to 1 of 4 maintenance dose rate (0.012, 0.024, 0.036, 0.048 MIU/kg/hour) which were continued for the subsequent 9 to 21 hours. The principal end point was the status of the infarct-related coronary artery 12 to 24 hours after the start of therapy, and before termination of rt-PA, in patients with initially patent vessels at 90 minutes. Of the 103 responders with repeat angiograms after a 9 to 21 hour maintenance infusion of rt-PA, a total of 17 (16.5%) patients reoccluded across all doses administered. There was no significant relationship between the maintenance dose rate and the incidence of reocclusion. However, ther was strong association between total dose of rt-PA administered and the incidence (16%) of serious or life-threatening bleeding exclusive of surgery. Other factors associated with serious bleeding included low body weight, female gender, and total duration of rt-PA infusion. Re-occlusion was independent of the 90 minute Thrombolysis in Myocardial Infarction trial perfusion grade and diameter of infarct vessel. Rethrombosis after establishment of early patency after rt-PA remains a significant problem that is un-affected by sustained rt-PA infusion in doses that can be tolerated. (Am J Cardiol 1992;69:1120-1127)

Fifty-nine consecutive patients presenting within 6 hours of the onset of symptoms of an acute myocardial infarction were treated with 150 mg of soluble aspirin orally, and either 70 or 100 mg of alteplase divided into 2 intrvenous bolus injections separated by 30 minutes. Dosage regimens were either 20 followed by 50 mg (group A), 50 followed by 20 mg (group B), or 50 followed by 50 mg (group C). Coronary angiography 60 minutes after the first bolus showed infarct-related coronary artery patency (Thrombolysis in Myocardial Infarction score 2 or 3) in 13 of 16 (81%) patients in group A, 12 of 17 (71%) in group B, and 10 of 11 (91%) in group C (overall patency rate at 60 minutes: 35 of 44 [80%] patients; 95% confidence interval 68 to 91%. At 90 minutes, patency rates were 15 of 20 (75%) patients in both groups A and B, and 18 of 19 (95%) in group C (overall patency rate 48 of 59 [81%] patients; 95% confidence interval 72 to 91%). Residual thrombus was identified with the 90-minute angiogram in 7 patients in group A, 5 in group B, and 3 in group C. Although there was no statistically significant difference in patency between the 3 dosage regimens at either 60 or 90 minutes there was a trend toward increased patency and more complete thrombolysis at 90 minutes in group C. No episodes of bradyarrhythmia, hypertension or cerebrovascular bleeding were observed after double bolus therapy. There were 7 episodes (12%) of reocclusion, and 3 deaths (5%) within 1-month follow-up. Double bolus alteplase therapy is a convenient and highly effective method of promoting early coronary artery patency. (Am J Cardiol 1991;68:1570-1574)

The three most commonly used thrombolytic (clot-dissolving) drugs in the US are streptokinase, alteplase or tissue plasminogen activator, and anistreplase. Urokinase, used more rarely, is also given for the treatment of myocardial infarction (heart attack). This acute condition results from the occlusion of one or more coronary arteries, which deliver blood to the heart itself. Thrombolytic therapy restores blood flow to coronary muscle (reperfusion) that has been deprived of blood as a result of arterial clots. The different pharmacological properties of these agents have important implications for their clinical use. The process of clot formation (thrombogenesis) after injury to a vessel wall or to atherosclerotic plaque (fatty deposits along the wall) is reviewed: the body's own thrombolytic system opposes this response. Thrombolytic drugs dissolve the fibrin network laid down in thrombogenesis: all these drugs activate plasminogen, the precursor of plasmin, which breaks fibrin apart. The relevant pharmacologic properties of the four drugs are listed in tabular form and discussed. Streptokinase can cause allergic reactions but these are rarely anaphylactic (severe, life-threatening reaction). Anistreplase may also cause allergies, but urokinase and alteplase do not. Rates of reperfusion and patency (extent to which the vessels remain open) are similar for all four agents. Hemorrhage after the administration of thrombolytic drugs is not the result of a reduction in levels of circulating fibrinogen, since the drugs that most reduce these levels (anistreplase, streptokinase, urokinase) are not more strongly associated with bleeding than alteplase, which has a less marked effect on fibrinogen levels. Such reductions in fibrinogen counteract a tendency for clots to form again. Many issues remain to be clarified regarding the advantages and drawbacks of thrombolytic drugs. (Consumer Summary produced by Reliance Medical Information, Inc.)

The purpose of this sM was to determine whether reperfusion of acute myocardial infarction (AMI) by recombinant tissue-type plasminogen activator (rt-PA) or percutaneous translu-minal coronary angioplasty, or both, would improve left ventricular (LV) function when it is measured several months later at rest or maximal bicycle exercise, or both. Radionuclide angiography was performed in 44 patients 5 months (range 6 weeks to 9 months) after AMI to assess function, and tomographic myocardial thallium201 imaging was performed at maximal exercise and delayed rest to determine whether there was any evidence of myocardial ischemia. As expected, no patient had chest pain or redistribution of a thallium defect during the exercise test, because patients has undergone angioplasty (n = 28) Or coronary bypass graft surgery (n =5) where clinically indicated for revascularization. The LV ejection fraction was plotted as a function of the time elapsed between the onset of chest pain and the time when coronary angiography confirmed patency of the infarct-related artery (achieved in 91% of 44 patients by rt-PA [in = 31] or percutaneous transluminal coronary angioplasty [n = 9]). Functional responses differed markedly between patients with anterior (n = 20) versus inferior (n = 24) wall AMI. LV ejection fraction during exercise correlated with time to reperfusion in patients with an anterior wall AMI (r = -0.58; standard error of the estimate = 11.9%; p [is not greater than]0.02) but not inpatients with an inferior AMI (r = 0.10; standard error of the estimate = 13.1%; difference not significant). LV ejection fraction was higher in patients with an anterior AMI reperfused early ([is less than or equal to] 4.5 hours, n = 8) Versus late ([is greater than] 4.5 hours or not at all, n = 12) at rest (44 [+ or -] 8 vs 32 [+ or -] 9%, p [is not greater than] 0.004) and exercise (53 [+ or -] 9 vs 33 [+ or -] 11%, p [is not greater than] 0.0005). in contrast, the ejection fraction of patients with an inferior wall AMI (n = 24) was not different from that of patients reperfused early (n = 17) versus late or not at all (n = 7), at rest (42 [+ or -] 8 vs 46 [+ or -] 12%; difference not significant) or exercise (46 [+ or -] 12 vs 55 [+ or -] 12; difference not significant). it is thus concluded that global LV function and functional reserve during exercise were both improved by reperfusion early ([is not greater than] 4.5 hours) in patients with an anterior wall AMI, but not in patients with an inferior wall AMI. Preservation of LV function during exercise was related to how early reperfusion was achieved in patients with anterior but not inferior wall AMI. (Am J Cardiol 1991;67:797-M), One of the effects of an acute myocardial infarction (AMI; heart attack) is that blood perfusion (flow) to the heart is diminished or interrupted for a period of time, which results in damaged tissue. Recent focus in the treatment of heart attacks has been on quickly resuming blood flow (reperfusion) to limit heart damage and to reduce mortality. Reperfusion is achieved by either giving thrombolytic agents, drugs that dissolve blood clots, or by using angioplasty, dilation of vessels by inflating an inserted balloon, or a combination of the two. This study examined whether early reperfusion when the heart attack involved the left ventricle (LV) improved the long-term functioning of the LV and thus the patient's prognosis. The study examined LV functioning as measured by LV ejection fraction (the proportion of blood in the ventricle that is pumped into the system with one heartbeat) in 44 AMI patients five months after the attack, who had undergone reperfusion therapy with either the drug recombinant tissue-type plasminogen activator (rt-PA) or percutaneous transluminal coronary angioplasty (PTCA) or both. Tests were done at rest and during exercise. Patients were grouped according to whether the heart attack affected the anterior or inferior wall of the LV and by time to reperfusion. Twenty patients had anterior wall AMI and 24 had inferior wall AMI. Among patients in the former group, resting LV ejection fractions were significantly greater in those who had early reperfusion (less than 4.5 hours) than in those who had later reperfusions, 44 versus 32 percent. During exercise the fractions were 53 percent in the early reperfused group and 33 percent in the late group, a significant difference. In the patients with inferior wall AMI, time to reperfusion did not affect ejection fraction and exercise did not increase it above resting levels. These results indicate that early reperfusion is useful in preserving LV function when the heart attack affects the anterior wall, but not when it affects the inferior wall. (Consumer Summary produced by Reliance Medical Information, Inc.)

A heart attack, or myocardial infarction, occurs when the blood supply to a portion of the heart muscle is suddenly cut off. This condition usually happens when a blood clot or fat deposits block one or more of the coronary arteries, which supply the heart. The treatment for myocardial infarction involves administering agents that dissolve blood clots and open the blocked arteries, restoring blood flow. Streptokinase and recombinant tissue plasminogen activator (rt-PA) are two agents that have been used to treat patients with myocardial infarction. Predictions were made that rt-PA would be twice as effective as streptokinase for the treatment of heart attack. However, these predictions were based on the results of studies using a test known as the 90-minute angiogram. This radiologic test measures the increase in blood flow to the heart muscle 90 minutes after a drug is given. The authors discuss the disadvantages of using this technique, and conclude that the 90-minute angiogram should not be used for comparing the effectiveness of streptokinase and rt-PA. A review of several recent studies, which included a total of 41,640 patients, indicated that rt-PA is not more effective than streptokinase in treating myocardial infarction, improving survival, or reducing the incidence of congestive heart failure and complications caused by hemorrhage. (Consumer Summary produced by Reliance Medical Information, Inc.)

A heart attack is a manifestation of a great many contributing factors, often including the development, over many years, of atherosclerotic plaques within the coronary arteries. The event precipitating a heart attack may be the rupture or ulceration of an atherosclerotic plaque. Platelets (blood cells involved in clotting) adhere to the ruptured plaque, aggregate, and initiate the development of a thrombus (blood clot). This thrombus is likely to become a thromboembolus, that is, likely to occlude (block) a smaller artery and impede blood flow to the heart muscle. A great step forward in the treatment of heart attack is thrombolysis, the use of enzymes, such as streptokinase or plasminogen activator, to dissolve such blood clots. If the blood clot dissolves and if blood flow to the oxygen-starved heart muscle can be restored before it is permanently damaged, the chances for recovery are excellent. However, improvements in this important therapeutic method are still possible, both in how quickly the thrombus is dissolved and in reducing the likelihood that a new clot will form after the first is dissolved. While heparin treatment is currently recommended as an anticoagulant adjunct therapy (with or immediately after thrombolysis), additional agents that act directly on platelets may prove to be of value. Aspirin has long been known to inhibit platelet function and blood clotting, but it is not yet known to what degree aspirin might be valuable as a part of thrombolytic therapy. Newly developed agents may also provide useful antiplatelet action, although these have, in general, been tested only in experimental animals. These include a monoclonal antibody that blocks the glycoprotein IIb/IIIa receptor on the platelets, and a chemically complex synthetic substance that binds to and inhibits the enzyme thrombin. It remains to be determined, however, if such substances will prove to be of value in clinical trials involving human patients. (Consumer Summary produced by Reliance Medical Information, Inc.)

Thrombolytic agents, such as streptokinase and tissue plasminogen activator, have produced a revolution in the treatment of heart attacks by virtue of their ability to dissolve blood clots that block important arteries in the heart. However, mortality from heart attacks remains enormous, and it is clear that thrombolytic drugs alone are not the final word in treatment. During or immediately after thrombolysis, anticoagulants such as heparin are being administered to improve the effectiveness of the clot-dissolving action. Other drugs may contribute to the success of thrombolytic therapy as well, particularly those capable of reducing the risk of damage to the heart muscle while the thrombolytic drugs are taking time to work. Such agents may include beta blockers and calcium antagonists. Beta blockers, which interfere with the beta adrenergic receptors in the heart muscle, reduce heart rate and blood pressure, and thus decrease the oxygen requirement of the heart muscle during this critical time. Furthermore, catecholamines are often elevated during a heart attack, and this effect is counteracted by beta blockers. While the physiological mechanisms that cause ischemic damage (related to oxygen deprivation) are uncertain, it seems that one of the major contributors is the entry of calcium ions into heart muscle cells. Calcium antagonists can block this influx and may provide a protective effect. Research in recent years has also pointed to magnesium ions as an important factor in heart attack. Many heart attack victims experience a transient decrease in blood levels of magnesium, and this may contribute both to the likelihood of arrhythmias (abnormal heart rhythms) and increased aggregability of platelets (clumping of cells involved in blood clotting). Magnesium supplementation should be given as needed, but further research will be necessary to evaluate the clinical effects of magnesium for the heart attack victim. Nitroglycerin, like beta blockers, may reduce the workload of the heart at a time when its oxygen supply is not adequate. Since angiotensin II may constrict the arteries during a heart attack, angiotensin-converting enzyme (ACE) inhibitors also offer promise for the treatment of heart attack. (Consumer Summary produced by Reliance Medical Information, Inc.)

In the first few hours after a myocardial infarction (heart attack), the use of thrombolytic enzymes, such as streptokinase or plasminogen activator, helps to dissolve the offending blood clot that is blocking a coronary artery and clear the vessel. However, after such treatment, the risk of developing a new clot, and therefore a second myocardial infarction, is high. While it may seem reasonable to use anticoagulant agents to reduce the risk of a second infarction, the actual advantage of this approach is highly controversial. The American College of Cardiology and the American Heart Association strongly recommend the use of heparin as an anticoagulant either with thrombolytic therapy or immediately thereafter. However, a major Italian study has reported that the use of heparin does not reduce mortality, but does increase the risk of bleeding as a complication. Thus, some researchers feel that the use of heparin therapy as an adjunct for thrombolytic therapy is not indicated. A review of the published studies of heparin reveals the possible reasons for these disagreements; variations in the dosage and the methods of administration may contribute to differences in the effects observed in different studies. Results seem to indicate that an injection of 5,000 Units of heparin followed by continuous intravenous infusion of 30,000 Units of heparin over the next 24 hours promotes an adequate anticoagulant response. However, the subcutaneous injection of 15,000 Units twice a days is not adequate. Furthermore, the major Italian study that initiated much of the controversy did find that 12,500 Units of heparin twice a day was effective in patients who had received streptokinase as their thrombolytic therapy, but when the same dose of heparin was used for patients who had received tissue plasminogen activator, it did not improve survival. The authors of the present review suggest that differences in the effects of streptokinase and plasminogen activator on the coagulation system may account for this discrepancy, and that higher doses of heparin may be required for effectiveness when plasminogen activator is used. (Consumer Summary produced by Reliance Medical Information, Inc.)

This study comprised a registry and an emergency department treatment trial using recombinant tissue plasminogen activator. During 1 year, 1,028 patients with documented acute myocardial infarction (AMI) were evaluated for eligibility for thrombolytic therapy. Of these, 221 patients (22%) were eligible for thrombolytic therapy under currently accepted criteria, 175 (79%) of them were correctly identified by emergency department physicians for thrombolytic therapy, and 160 were enrolled in the trial. Only 3 patients (2%) enrolled by emergency department physicians did not subsequently evolve documented AMI. In all, 807 patients (78%) were ineligible for thrombolytic therapy: 335 (33%) because of [is greater than or equal to]1 contraindications, 364 (36%) because of nondiagnostic electrocardiograms on presentation, and 105 (10%) because of age [is greater than]75 years, or [is greater than]6 hours of chest pain at presentation, or both. Mortality in treated patients at 14 days was 5.6%, and survival at 1 year was 92%. The mean time from hospital arrival to thrombolytic treatment was 55 [+ or -] 27 minutes. Initial management of AMI with recombinant tissue plasminogen activator in the emergency department provided rapid and safe treatment comparable to that reported in trials that started treatment in the coronary care unit. The proportions of eligible patients could be increased from 1 in 5 to 1 in 3, if patients currently excluded only because of age [is greater than]75 years or because of [is greater than]6 hours of chest pain were offered treatment. (Am J Cardiol 1990;66:1298-1303), In acute myocardial infarction (AMI, or heart attack), the blood supply to the heart is impaired by the occlusion of one or more of the coronary arteries, usually by a blood clot. Myocardial infarction results in damage to the heart muscle and may cause death. A recognized treatment for AMI is the administration of thrombolytic agents, such as tissue plasminogen activator (TPA), which dissolve the thrombi, or clots, occluding the coronary arteries. To evaluate the practicality, benefits, and safety of emergency room physicians administering TPA to patients diagnosed as having AMI, 1,028 cases were reviewed. The patients had been admitted to hospitals in the Seattle-Tacoma metropolitan area with diagnoses of presumptive AMI. A total of 807 patients were ineligible for TPA treatment for various reasons, including having had more than one AMI incident, symptoms for more than six hours, age over 75 years, high blood pressure, and recent injury. Of the 221 eligible patients, 7 refused TPA treatment, 46 were not treated because they were incorrectly evaluated in the emergency room as being ineligible, and 168 were treated. The average time to initiate TPA treatment was 55 minutes after hospital admission. At 14 days following AMI, 5.6 percent of the TPA-treated patients had died; at one-year follow-up, the survival rate was 92 percent. If the age and time-from-onset criteria for eligibility were relaxed so that patients over 75 years of age and those with AMI symptoms of more than six hours duration could be treated, the percentage of eligible patients would rise from 20 percent to over 30 percent. Emergency room administration of TPA appears to be as safe and efficacious as administration begun in the coronary care unit. (Consumer Summary produced by Reliance Medical Information, Inc.)

This study assesses whether administration of recombinant tissue-type plasminogen activator (rt-PA) up to 8 hours after onset of symptoms of acute myocardial infarction (AMI) may result in a significant improvement in left ventricular function. Sixty patients were classified into 3 groups: group A (n = 21) received rt-PA within 4 hours from symptom onset; the remaining 39 patients, admitted between 4 and 8 hours, were randomized into 2 groups--group B (n = 19) received rt-PA, and group C (n = 21) was treated with conventional therapy. Coronary and left ventricular angiograms were recorded 8 to 10 days after rt-PA administration. The patency rate of the infarct-related artery was 76% in group A, and 63 and 35% in group B and C, respectively. The Thrombolysis in Myocardial Infarction trial perfusion grade was higher in group A and B than in group C (A vs C: p [is less than]0.005; B vs C: p [is less than]0.01). Left ventricular ejection fraction was significantly higher in group A (60.2 [+ or -] 10%) and B (54.7 [+ or -] 12%) compared with group C (44.2 [+ or -] 12%) (A vs C: p [is less than]0.01; B vs C: p [is less than]0.05). Regional wall motion of the entire ischemic zone was better in group A and B than in group C (A vs C: p [is less than]0.001; B vs C: p [is less than]0.01). In contrast, the kinesis of the central ischemic zone was significantly better in group A than in both group B and C (A vs B: p [is less than]0.05; A vs C: p [is less than]0.001). The number of hypokinetic, akinetic and dyskinetic segments were lower in group A and B than in group C (A vs B: p [is less than]0.01, B vs C:p [is less than]0.05 and A vs C: p [is less than]0.01 and B vs C: p [is less than]0.01, respectively). Thus, these data confirm the efficacy of early thrombolysis and suggest that late reperfusion may act beneficially in preserving left ventricular volumes and function. (Am J Cardiol 1990;66:1281-1286), In acute myocardial infarction (AMI, or heart attack), the blood supply to the heart is impaired by the blockage of one or more coronary arteries; this results in damage to the heart muscle and may cause death. The treatment of choice for AMI is prompt administration of thrombolytic agents, which break up the clot blocking the coronary artery, restoring blood flow to the heart. There is controversy over how long after the beginning of an AMI thrombolytic treatment can be administered before heart damage becomes irreversible. To determine the effects of late thrombolysis on the outcome of AMI, 60 patients admitted to a coronary care unit with the diagnosis of AMI were assessed. Recombinant tissue-type plasminogen activator (rt-PA; a substance that causes dissolution of fibrin clots) was administered directly into the blocked coronary artery of patients who were diagnosed with AMI early (less than four hours after the onset of symptoms - early treatment group). A second group, in whom the diagnosis of AMI was made between four and eight hours after symptom onset, received rt-PA later in the course of the heart attack (late treatment group). A third group, also with delayed diagnosis of AMI, received only conventional therapy (vasodilators and anticoagulant drugs). On most indices of heart function, the early and late treatment groups tested significantly better than the group who received conventional therapy; patency of the infarct-related artery, contractility of the left ventricle, and motility of the ischemic (blood deprived) area were all comparably improved after either early or late thrombolysis, compared with conventional therapy. One index of cardiac function, the number of segments of the heart with impaired motility, showed less dramatic improvement in the late treatment group than in the early treatment group, but the heart function of both rt-PA groups was significantly better than the conventional therapy group. (Consumer Summary produced by Reliance Medical Information, Inc.)

Narrowing or occlusion of the coronary arteries (which supply the heart) causes a decrease in the cardiac blood supply (myocardial ischemia) and can result in pain in the region of the heart (angina pectoris). This pain is exacerbated by exercise and stress. When the pain worsens, and begins to occur even during periods of rest, the condition is referred to as unstable angina. This development frequently precedes acute myocardial infarction (heart attack; an acute total blockage of one or more of the coronary arteries resulting, if not promptly treated, in permanent cardiac damage and even death). Unstable angina usually responds to treatment with vasodilator medications (which relax blood vessels), but a subset of patients do not improve with this therapy, and are at great risk of suffering a heart attack. Drugs that prevent clotting (such as heparin) and that dissolve existing blood clots (such as tissue-type plasminogen activator or streptokinase) may have beneficial effects in this group of high-risk patients. To investigate this theory, 24 vasodilator-resistant unstable angina patients were randomly assigned to receive either heparin alone or heparin plus recombinant tissue-type plasminogen activator (rt-PA). Recurrent ischemic attacks were documented in 9 of 12 patients who received heparin alone; none of the patients who were given rt-PA experienced these symptoms. Statistical modeling demonstrated that there was a significantly greater tendency among the rt-PA patients to remain symptom-free over time (up to three days). Quantitative coronary angiography (an X-ray technique for visualizing the coronary arteries) did not reveal any change in the size of ischemia-related heart lesions after either treatment. Treatment with rt-PA does not confer a permanent improvement in coronary artery status nor obviate the need for procedures which improve cardiac blood flow; however, rt-PA may allow these procedures to be performed in more optimal circumstances. (Consumer Summary produced by Reliance Medical Information, Inc.)

Alteplase Genentech Low-dose t-PA for catheter clearance Alteplase has been approved in a new 2-mg dose strength for a new indication: restoration of function to central venous access devices (CVADs, [...]

Abstract Objectives--To determine the incidence of catheter related thrombosis and to test the efficacy of recombinant tissue type plasminogen activator (rt-PA) in preterm infants. Study design--From January 1995 to December [...]

In the prospective study, the authors found that in 116 events, rtPA significantly increased blood flow (Qb) from a mean of 131.6 ml/min to 255.6 ml/min in the partially occluded catheters and was 87.5% successful in restoring flow to [is greater than] 200 ml/min in 40 occluded catheters. In the retrospective study, 42 events using urokinase significantly increased flow from 131.2 ml/min to 176.2 mi/min. The comparison rtPA group with 58 events saw an even greater increase, from 140.5 ml/min to 255.3 ml/min. In those catheters that were occluded, the urokinase restored patency ([is greater than] 200 ml/min) in 42.9%, whereas the rtPA had an efficacy rate of 88.2%. The authors concluded that rtPA was an effective thrombolytic for restoring catheter patency and more effective than urokinase in opening catheters that were completely occluded., Prospective Evaluation of Recombinant Tissue Plasminogen Activator (rtPA) with a Retrospective Comparison for Urokinase in Re-Establishing Blood Flow through Occluded Hemodialysis Catheters. J.M. Zacharias, C. Weatherston, & L.M. Vercaigne, Manitoba, [...]

Objective: To assess, by systematic review, the efficacy and safety of recombinant tissue plasminogen activator (rt-PA) in the treatment of lower extremity deep venous thrombosis (DVT). A secondary objective is [...]

Clinical question Does primary angioplasty in myocardial infarction produce better long-term outcomes than tissue-type plasminogen activator (t-PA)? Background The Primary Angioplasty in Myocardial Infarction (PAMI) Trial[1] found increased survival in [...]

A Case Series Report Background and study objective: Echocardiographic detection of right heart thromboemboli (RHTE) during pulmonary embolism (PE) shows an uncommon but life-threatening event. The treatment of this condition [...]