Ventricular arrhythmias during treatment with alteplase (recombinant tissue plasminogen activator) in suspected acute myocardial infarction

Continuous electrocardiography during the first 24 hours of a stay in a coronary care unit was used to record ventricular arrhythmias during treatment with alteplase (recombinant tissue plasminogen activator) or placebo. Recordings were made on 378 of the 436 patients admitted to a double blind trial of alteplase or placebo in one participating centre of the Anglo-Scandinavian study of early thrombosis (ASSET), patients being selected according to the availability of recorders. Of these, 309 (158 given alteplase and 151 placebo) had greater than 5 hours of analysable data. Most of the arrhythmias were recorded in patients with an in hospital diagnosis of myocardial infarction. Ventricular couplets and ventricular tachycardia were significantly more common in the patients treated with alteplase. Further, in patients with myocardial infarction who had ventricular extrasystoles, couplets, or ventricular tachycardia type a, the number of hours in which each arrhythmia was recorded was significantly higher in the alteplase group. The various ventricular arrhythmias in the alteplase group tended to cluster in the first 4-12 hours of the recordings. During the first 24 hours admission there were four episodes of ventricular fibrillation in the alteplase group and five in the placebo group of taped patients. By one month there had been 18 deaths in these 309 patients (alteplase four, placebo 14). These bore no relation to any recorded arrhythmia. Clinical records for the patients with no or minimal tape data yielded six further episodes of ventricular fibrillation during the first 24 hours (three in the alteplase group and three in the placebo group). Of the total 436 patients, 10 of the 218 patients in the alteplase group had died by one month compared with 22 of the 218 patients treated with placebo. The use of alteplase increases the incident of non-life threatening ventricular arrhythmias. These results, however suggest that arrhythmia after thrombolysis in the pre-hospital phase may be less of a problem than it is perceived to be.     

Ventricular arrhythmias during treatment with alteplase (recombinant tissue plasminogen activator) in suspected acute myocardial infarction.

Continuous electrocardiography during the first 24 hours of a stay in a coronary care unit was used to record ventricular arrhythmias during treatment with alteplase (recombinant tissue plasminogen activator) or placebo. Recordings were made on 378 of the 436 patients admitted to a double blind trial of alteplase or placebo in one participating centre of the Anglo-Scandinavian study of early thrombosis (ASSET), patients being selected according to the availability of recorders. Of these, 309 (158 given alteplase and 151 placebo) had greater than 5 hours of analysable data. Most of the arrhythmias were recorded in patients with an in hospital diagnosis of myocardial infarction. Ventricular couplets and ventricular tachycardia were significantly more common in the patients treated with alteplase. Further, in patients with myocardial infarction who had ventricular extrasystoles, couplets, or ventricular tachycardia type a, the number of hours in which each arrhythmia was recorded was significantly higher in the alteplase group. The various ventricular arrhythmias in the alteplase group tended to cluster in the first 4-12 hours of the recordings. During the first 24 hours admission there were four episodes of ventricular fibrillation in the alteplase group and five in the placebo group of taped patients. By one month there had been 18 deaths in these 309 patients (alteplase four, placebo 14). These bore no relation to any recorded arrhythmia. Clinical records for the patients with no or minimal tape data yielded six further episodes of ventricular fibrillation during the first 24 hours (three in the alteplase group and three in the placebo group). Of the total 436 patients, 10 of the 218 patients in the alteplase group had died by one month compared with 22 of the 218 patients treated with placebo. The use of alteplase increases the incident of non-life threatening ventricular arrhythmias. These results, however suggest that arrhythmia after thrombolysis in the pre-hospital phase may be less of a problem than it is perceived to be.     

Plasma and platelet plasminogen activator inhibitor-1 in patients with acute myocardial infarction

Several studies have demonstrated an increased level of plasma plasminogen activator inhibitor-1 (PAI-1) in patients with coronary artery disease (CAD). However, the concentration of PAI-1 in platelets, which accounts for more than 90% of the blood PAI-1, is unknown in these patients. The present study evaluated the concentrations of PAI-1 and several fibrinolytic factors in the plasma and platelets of patients with CAD and the serial changes in patients with acute myocardial infarction (AMI). All 72 subjects had coronary angiography and were divided into 3 groups: CAD(-) group without coronary artery stenosis or myocardial ischemia (n=20), CAD(+) group with either stable angina pectoris (n=18) or old myocardial infarction (n=12) with coronary artery stenosis, and the AMI group admitted within 24h of symptom onset who underwent successful percutaneous transluminal coronary angioplasty (n=22). The concentrations of plasma PAI-1, tissue plasminogen activator (t-PA), and t-PA x PAI-1 complex were similar in the CAD(-) and CAD(+) groups, but were greater on day 1 in the AMI group compared with the 2 CAD groups. There were no significant differences between the 3 groups in the plasma concentrations of thrombin antithrombin III complex (TAT), alpha2-plasmin inhibitor-plasmin complex (PIC), beta-thromboglobulin (beta-TG), and platelet factor 4 (PF-4). The platelet PAI-1 concentrations did not differ between the CAD(-) and CAD(+) groups, but was greater on day 1 in the AMI group compared to the CAD groups. The platelet beta-TG and PF-4 were similar between the 3 groups. In the AMI group, both the plasma and platelet PAI-1 concentrations were greater on day 1, but the plasma PAI-1 rapidly decreased by day 5 and remained low on day 28 compared with day 1. The platelet PAI-1 concentration gradually decreased by day 5 and was further decreased by day 28. The serial changes of the plasma t-PA and t-PA PAI-1 complex during the course of AMI were similar to those of the plasma PAI-1. A positive correlation was found between the plasma and platelet PAI-1 in all 72 patients, but not in the AMI group alone. These results suggest that the PAI-1 that has accumulated in platelets at the onset of AMI might be released in large amounts into the plasma, resulting in an increase in thrombus formation.     

Accelerated plasminogen activator inhibitor may prevent late restenosis after coronary stenting in acute myocardial infarction

BACKGROUND: Although acceleration of plasma plasminogen activator inhibitor-1 (PA-1) level after emergent coronary angioplasty in acute myocardial infarction (AMI) has been documented, its pathophysiologic role is still unknown. HYPOTHESIS: This study was designed to elucidate the role of PAI-1 in the development of restenosis after primary coronary stenting in AMI. METHODS: We selected for this study 66 patients with AMI, who underwent primary coronary stenting for infarct-related coronary artery lesions in an emergent situation. In all patients, plasma PAI-1 level was measured at admission, and at 3 h, 24 h, 48 h, and 1 month after coronary stenting. RESULTS: At admission, the PAI-1 level was equivalent in 24 patients who experienced restenosis and in 42 patients without restenosis (28 +/- 4 vs. 29 +/- 4 ng/ml). In patients with restenosis, the levels did not change during the course after coronary stenting. In patients without restenosis, however, the level significantly increased at 3 h (48 +/- 9 ng/ml, p < 0.001), 24 h (42 +/- 9, p < 0.01), and 48 h (38 +/- 7, p < 0.05) after coronary stenting, and was restored to the level equivalent to that at admission (27 +/- 2 ng/ml) I month aftercoronary stenting. The PA-1 level at 3 h after coronary stenting in patients without restenosis was significantly higher (p < 0.05) than the level (33 +/- 6 ng/ml) in patients with restenosis. Multiple logistic regression analysis indicated that the PAI-1 level 3 h after coronary stenting was an independent predictor of restenosis (Wald chi2 = 3.826, p = 0.019, odds ratio 0.921, 95% confidence interval 0.866-0.961). CONCLUSION: Accelerated PAI-1 after coronary stenting in patients with AMI may protect against the development of late restenosis.     

Effect of activated protein C on plasma plasminogen activator inhibitor activity in patients with acute myocardial infarction treated with alteplase: comparison with unfractionated heparin

OBJECTIVES: We examined whether activated protein C (APC) is an effective conjunctive therapy to thrombolysis in patients with ST-segment-elevated acute myocardial infarction (AMl). BACKGROUND: Activated protein C possesses both systemic anticoagulant and anti-inflammatory properties. It has been also shown to enhance fibrinolysis by inhibiting plasminogen activator inhibitor (PAI) activity in vitro. METHODS: After successful thrombolysis with alteplase, study patients were assigned to receive one of the two conjunctive therapies for 48 h intravenously: human plasma-derived APC at 0.06 mg/kg per day (APC group, n = 9) or unfractionated heparin at 100 to 400 U/kg per day, adjusted to maintain an activated partial thromboplastin time at 1.5 to 2 times of the control level (heparin group, n = 10). RESULTS: Adverse events, including reocclusion of the recanalized infarct-related coronary artery and major or minor hemorrhagic complications, occurred more frequently in the heparin group (4 of 10 cases) than in the APC group (none of 9 cases) (p = 0.033). In the heparin group, plasma PAI activity (IU/ml, median value [range]) was increased continuously from 8 to 24 h after thrombolysis and peaked at 24 h (30.9 [11.3 to 38.5]); on the other hand, it was not increased in the APC group at 24 h after thrombolysis (11.3 [0.0 to 31.0], p < 0.01 vs. heparin group). CONCLUSIONS: Administration of APC suppressed increasing of plasma PAI activity observed after thrombolysis in patients with AMI. The effect of APC could be more eligible, compared with heparin, as a conjunctive regimen to thrombolysis in AMI patients.     

Streptokinase and tissue plasminogen activator in acute myocardial infarction

The use of thrombolytic agents for the treatment of myocardial infarction is increasing. Many community hospitals are infusing SK intravenously and those with cardiac catheterization laboratories often use intracoronary SK and angioplasty. Tissue plasminogen activator is undergoing extensive clinical trials, and reports of this research should add to our knowledge of this new therapy. Recently, benefits from thrombolytic therapy such as increased ejection fraction, improved regional wall motion, and short-term decreases in mortality have been documented. Both the GISSI trial that recruited 11,712 patients in Italy and the Netherlands trial documented significant short-term decreases in mortality after therapy with SK compared with control groups. As this information reaches the medical community, we may see an increase in the use of thrombolytic therapy during acute myocardial infarction. Additionally, community education service organizations should reemphasize the importance of seeking help early after the signs and symptoms of acute myocardial infarction appear to promote early treatment and potential salvage of greater amounts of myocardium. The long-term prognosis of patients who have been successfully reperfused and the best management after thrombolytic therapy is not yet known. Future problems and benefits from this therapy are still to be determined.     

Plasma fibrinopeptide A levels in patients with acute myocardial infarction treated with alteplase. Correlation with concomitant heparin, coronary artery patency, and recurrent ischemia. The European Cooperative Study Group.

BACKGROUND. Fibrin generation during and after therapy with alteplase may depend on the level of concomitant anticoagulation. The hypothesis that fibrinopeptide A (FPA) levels, as markers of ongoing in vivo fibrin formation, correlate with the angiographic and clinical outcome of thrombolysis is tested. METHODS AND RESULTS. Serial plasma FPA levels were determined in 334 patients of the randomized European Cooperative Study Group trial comparing heparin versus placebo plus alteplase and aspirin in patients with acute myocardial infarction. Median FPA levels (with the 10th to 90th percentiles) were 21 ng/ml (2-390 ng/ml) before treatment in placebo-allocated patients (n = 166) and increased to 49 (15-580), 34 (4-320), 27 (2-240), 29 (2-430), and 30 (3-390) ng/ml after 0.75, 3, 12, 24, and 36 hours, respectively. In heparin-allocated patients (n = 168), median baseline FPA values were 18 ng/ml (2-210 ng/ml) and decreased to 6 (1-110), 5 (1-75), 5 (1-60), 7 (1-100), and 10 (1-170) ng/ml at corresponding time points (p less than 0.0001 for the difference at each time point). Adequate anticoagulation, defined as no activated partial thromboplastin time value below twice the pretreatment value at 3, 12, 24, and 36 hours after initiation of treatment, was obtained in 48 patients assigned to heparin. It was associated with normal median FPA levels (less than or equal to 4 ng/ml) at all time points compared with 12 (2-80), 16 (2-240), and 15 (2-240) ng/ml at 12, 24, and 36 hours, respectively, in heparin-assigned but inadequately anticoagulated patients (n = 102, p less than 0.001 for each time point). In the heparin-treated group, median FPA values tended to be lower at all time points in patients with patent vessels than in patients with occluded arteries, but the difference was significant only at 24 hours (p = 0.04). FPA levels did not correlate with clinically apparent recurrent ischemia or with left ventricular thrombosis on two-dimensional echocardiography. CONCLUSIONS. During and after thrombolytic therapy with alteplase, the enhanced fibrin generation is suppressed by sustained concomitant anticoagulation with intravenous heparin. Adequate anticoagulation warrants individual titration of the heparin dose. High plasma FPA levels 24 hours after alteplase therapy are specific but insensitive markers of vessel occlusion in anticoagulated patients. They do not correlate with clinical outcome.     

Downregulated expression of plasminogen activator inhibitor-1 augments myocardial neovascularization and reduces cardiomyocyte apoptosis after acute myocardial infarction

OBJECTIVES: The aim of this study was to examine whether selective plasminogen activator inhibitor type 1 (PAI-1) downregulation in the acutely ischemic heart increases the myocardial microvasculature and improves cardiomyocyte (CM) survival. BACKGROUND: Endogenous myocardial neovascularization is an important process enabling cardiac functional recovery after acute myocardial infarction. Expression of PAI-1, a potent inhibitor of angiogenesis, is induced in ischemic heart tissue. METHODS: A sequence-specific catalytic deoxyribonucleic acid (DNA) enzyme was used to reduce PAI-1 levels in cultured endothelial cells and in ischemic myocardium. At the time of coronary artery ligation, rats were randomized into three groups, each receiving an intramyocardial injection (IMI) of a single dose at three different sites of the peri-infarct region consisting, respectively, of DNA enzyme E2 targeting rat PAI-1 (E2), scrambled control DNA enzyme (E0), or saline. Cardiomyocyte apoptosis, capillary density, and echocardiography were studied two weeks following infarction. RESULTS: The E2 DNA enzyme, which efficiently inhibited rat PAI-1 expression in vitro, induced prolonged suppression (>2 weeks) of PAI-1 messenger ribonucleic acid and protein in rat heart tissues after a single IMI. At two weeks, hearts from experimental rats had over five-fold greater capillary density, 70% reduction in apoptotic CMs, and four-fold greater functional recovery compared with controls. CONCLUSIONS: These results imply a causal relationship between elevated PAI-1 levels in ischemic hearts and adverse outcomes, and they suggest that strategies to reduce cardiac PAI-1 activity may augment neovascularization and improve functional recovery.     

Reactive protein,plasminogen activator inhibitor type-1 （PAI-1） levels,PAI-1 promoter 4G/5G polymorphism and acute myocardial infarction

Objective To investigate the relationship between CRP, plasminogen activator inhibitor type 1 （PAI-1） levels, PAI-1 gene promoter 4G/5G polymorphism and the type of acute myocardial infarction （ST elevation myocardial infarction, STEMI vs the non-ST elevation Myocardial infarction, NSTEMI）. Methods One hundred seventy-six consecutive patients with AMI were included for the study, of whom 60 had STEMI and 56 had NSTEMI, and 60 adults without cardiovascular and cerebrovascular disease were selected as controls. Blood samples were obtained from patients within 6 h of AMI and the plasma PAI-1, CRP, and the gene polymorphism were measured. Results Plasma levels of PAI- 1 and CRP were higher in AMI groups, compared those in the control group, and plasma levels of PAI-1 were significantly higher in patients with STEMI compared to those with NSTEMI （80.12ng/ml VS.73.01ng/ml, P 〈0.01）, while CRP levels were not significantly different between patient with STEMI and NSTEMI （3.87 ± 0.79 mg/ml VS.4.01 ±0.69mg/ml, P〉0.05）. PAI-1 levels presented a significant correlation with CRP levels in the NSTEMI subjects. However, PAI-1 and CRP levels could explain the lack of a significant relationship between them in control and STEMI subjects.The frequencies of 4G/4G genotype in the AMI group were higher than those in the control group and higher in patient with STEMI than in patient with NSTEMI. Plasma levels of PAI-1 in subjects with 4G/4G genotype were significantly increased as compared to those in subjects with 4G/5G and 5G/5G genotype. Conclusions Plasma PAI-1 levels were associated with different myocardial infarction type, and PAI-1 promoter 4G/5G polymorphisms and CRP may be related to plasma PAI-1 levels     

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.     

Spinal epidural hematoma associated with tissue plasminogen activator treatment of acute myocardial infarction.

We report a case of tissue plasminogen activator-associated spinal epidural hematoma in a patient who underwent treatment for myocardial infarction. Diagnostic magnetic resonance imaging was used within 24 hr of coronary artery stent implantation. We review the literature on thrombolytic-associated epidural spinal hematoma and discuss its management. Cathet. Cardiovasc. Intervent. 48:390-396, 1999.     

One-year follow-up after recombinant tissue plasminogen activator administered to patients with acute myocardial infarction

Of 106 patients seen within 4 h of chest pain with 107 episodes of acute myocardial infarction, nine died before or during hospitalization mainly from cardiogenic shock, and four died during the next year, three were sudden deaths. The 93 survivors were reviewed at a mean of 53 (range 49-70) weeks after infarction. Of these 93, 18 had had attempted angioplasty (successful in 12) and 15 had had coronary artery bypass grafting (including one patient who had coronary artery bypass grafting performed after unsuccessful angioplasty). The remaining 61 patients continued on medical therapy only. During the one-year follow-up two patients suffered reinfarction and a further 22 had one or more cardiac admissions, mostly for chest pain. At review, 22 patients had angina (16 New York Heart Association Grade I or II) and five dyspnoea (all NYHA Grade II). Forty-three patients were taking oral nitrates, 53 were receiving calcium antagonists, 54 were using betablocking agents and 73 used anti-platelet agents. However, many of these patients continued on anti-anginal therapy prophylactically after their myocardial infarction, without continuing chest pain. Thus after recombinant tissue plasminogen activator therapy and following hospital discharge the mortality rate for patients with acute myocardial infarction was four out of 97 (4.1%) and reinfarction rate among survivors was two out of 93 (2.2%). Although the incidence of cardiac symptoms was low this may be partly due to the high incidence of angioplasty and coronary artery grafting, together with the use of anti-anginal agents.     

纤溶酶原激活物抑制剂-1与急性心肌梗死关系的研究

目的探讨纤溶酶原激活物抑制剂-1(PAI-1)在急性心肌梗死(AMI)发病中的作用。方法应用发色底物法测定中国汉族AMI患者56例(男44,女12,平均年龄67±10岁)和正常对照组55例(男42,女13,年龄68±8岁)血浆PAI-1活性,并分析环境因素对PAI-1水平的影响。结果 (1)AMI组和正常对照组的血浆PAI-1水平分别为O.90±O.13Au/ml和O.72±O.13Au/ml,两组间比较有显著性差异(P<0.001)。(2)吸烟、高血压病史、既往血栓性疾病病史、冠心病家族史、体重指数(BMI)、三酰甘油(TG)、血糖水平均与血浆PAI-1水平呈正相关,多元逐步回归分析显示,高血压病史、冠心病家族史是血浆PAI-1水平的独立预测因素。结论血浆PAI-1水平增加是心肌梗死(MI)的危险因素;(2)高血压、冠心病家族史为PAI-1水平的独立决定因素。     

Vasculitis complicating treatment with intravenous anisoylated plasminogen streptokinase activator complex in acute myocardial infarction

Vasculitis developed in six of 253 patients treated with intravenous anisoylated plasminogen streptokinase activator complex (APSAC) after acute myocardial infarction. All patients recovered spontaneously with no evidence of renal impairment and no long term sequelae. Although leucocytoclastic vasculitis and serum sickness have been reported after streptokinase treatment, such allergic reactions have not been described as a complication of other thrombolytic agents.     

Association of patency of the infarct-related coronary artery with plasma levels of plasminogen activator inhibitor activity in acute myocardial infarction.

To examine the fibrinolytic capacity in patients with acute myocardial infarction (AMI), baseline levels of plasma plasminogen activator inhibitor (PAI) activity and tissue-type plasminogen activator (t-PA) antigen were measured in 47 patients with Q-wave AMI who underwent emergent coronary angiography 3.0 +/- 0.2 hours after the symptom onset. They received intracoronary injection of urokinase if their infarct-related arteries were occluded. They were classified into 3 groups according to the patency of the infarct-related artery before and after thrombolytic therapy: the patent group (13 patients), the recanalized group (23 patients) and the occluded group (11 patients). The mean level of plasma PAI activity (IU/ml) was higher in patients with AMI as a whole than in the control group (12.8 +/- 1.6 vs 5.4 +/- 0.5, p less than 0.01). The level was lower in the patent group (3.0 +/- 1.1) and higher in the recanalized (18.6 +/- 2.2) and occluded (10.8 +/- 2.5) groups than in the control group (each p less than 0.01). The level was lower in the occluded than in the recanalized group (p less than 0.01) and 62% of the patients in the occluded group had levels within range of the control group. The mean level of plasma t-PA antigen (ng/ml) was higher in patients with AMI as a whole than in the control group (10.3 +/- 0.8 vs 5.8 +/- 0.3, p less than 0.01). There was no difference in the level among the 3 groups with AMI.(ABSTRACT TRUNCATED AT 250 WORDS)