Intravenous Infusion Of Streptokinase Research Articles

Killip classification and baseline heart rate can be used to predict streptokinase‑induced hypotension in acute myocardial infarction

Streptokinase is the thrombolytic therapy of choice for acute myocardial infarction in hospitals without cardiac facilities. Streptokinase‑induced hypotension is one of the common adverse drug reactions and is usually observed within 30 min of an intravenous streptokinase infusion. The present study aimed to identify predictive clinical parameters for the development of hypotension in patients with acute myocardial infarction. The present retrospective study involved data transcription from National Indicator Approach (NIA) records of acute myocardial infarction recorded between 2015 to 2018. Multivariate analysis was performed to evaluate potential predictors of streptokinase‑induced hypotension and to determine the association between selected clinical variables in patients with streptokinase‑induced hypotension. The present study included a total of 412 patients with acute myocardial infarction administered streptokinase. The majority (n=258, 62.6%) did not develop any complication from the therapy, whereas 109 (26.5%) developed hypotension at 18.5 (interquartile range, 10.00) min from the initiation of therapy. Multiple logistic regression analysis revealed that with every one‑unit increment in the baseline heart rate, the risk of hypotension was reduced by 2.6%. Additionally, patients classified as Killip class III and IV were at an increased risk (5‑fold) of developing hypotension as compared with those classified as Killip I. Therefore, as demonstrated herein, these predictive factors may assist clinicians in identifying susceptible individuals and may encourage vigilance when delivering streptokinase therapy.

Acute myocardial infarction associated with right bundle branch block and changeable trifascicular block: a case report

Rationale: Acute myocardial infarction in the presence of right bundle branch block. Patient concerns: A 70-year-old, male heavy smoker presented with angina and hypertension. Interventions: Electrocardiography, intravenous nitroglycerin infusion, intravenous streptokinase infusion. Diagnosis: Acute myocardial infarction in the presence of with changeable trifascicular heart block. Outcomes: Dramatic clinical improvement with electrocardiographic ST-segment (whether elevation or reciprocal ST-depression) resolution. Lessons: Acute myocardial infarction may be associated right bundle branch block. Accompanied trifascicular heart block had pre-streptokinase left anterior fascicular block with left axis deviation and post-streptokinase left posterior fascicular block with right axis deviation.

Acute Myocardial Infarction During Thrombolysis of Mechanical Aortic Valve Thrombosis Associated With Heparin-Induced Thrombocytopenia

We report a case of a 60-year-old man with obstructive aortic prosthetic valve thrombosis (APVT). He was treated with low-dose (25 mg) slow infusion (6 hours) of intravenous tissue plasminogen activator (t-PA), and he suffered acute anterior myocardial infarction (MI) at the fourth hour of t-PA infusion. Infusion was kept on, and coronary reperfusion and successful lysis of APVT were achieved. Intravenous unfractionated heparin (UFH) was then started, however, on the third day following heparin treatment, heparin-induced thrombocytopenia (HIT) was recognized by a drop in the platelet count and rethrombosis of the prosthetic valve. Although no nonheparin anticoagulant was available, intravenous continuous infusion of streptokinase (SKZ) 250,000 U per day was administered for 5 days followed by transition to warfarin therapy. Successful lysis of the APVT was again achieved with this regimen and the patient was discharged after uneventful recovery. The patient remained well at 6 months and 1 year follow-up.

Intravenous streptokinase infusions in acute myocardial infarction. Restoring patency of occluded thrombotic coronary vessels (author's transl)

Intravenous treatment over 30 minutes with 500 000 U streptokinase was given to 21 patients with acute myocardial infarction. Serial measurements of serum CK-MB activity made recanalisation of the infarcted artery likely in 3 patients. Selective coronarography was performed in 18 patients during the acute infarction phase. Angiographic follow-up investigations were done 24 hours and after 3 weeks. In 3 cases only subtotal occlusion of the infarcted coronary artery was seen during the acute phase. A thrombus demonstrated in two patients could be lysed. In 8 out of 15 patients with complete coronary artery occlusion the infarcted vessel was reopened 20-60 minutes after onset of intravenous streptokinase infusion. In a further 4 patients recanalisation was observed 60-140 minutes after passing a guide wire or during an additional intracoronary infusion of streptokinase. The infarcted vessel remained occluded in 3 patients, one of whom died following myocardial rupture. In 12 patients with recanalisation of the infarcted artery during the acute phase a premature maximum of serial CK-MB serum activity was seen after 13.5 +/- 2.9 hours in comparison with 20.9 +/- 5.3 hours in 122 patients treated conventionally. Serial enzyme determinations allow indirect conclusions as to a rapid recanalisation of an infarcted blood vessel.

Development and Pathophysiological Basis of Thrombolytic Therapy in Acute Myocardial Infarction: Part IV

Acute and day 10 to 14 recanalization rates with intracoronary thrombolytic and/or spasmolytic therapy were determined in the First Mt. Sinai‐N.Y.U. Reperfusion Trial (1984). Recanalization of total occlusion was accelerated by intracoronary streptokinase, the first proven potentially beneficial effect of thrombolytic therapy. Intravenous administration of thrombolytic agents, including t‐PA, was less effective in accelerating recanalization than intracoronary streptokinase as assessed by 90‐minute rates of TIMI‐III flow. In clinical practice the greater ease of intravenous administration outweighed this disadvantage, but intracoronary administration was uniquely suited to analyze the pathophysiological principles of reperfusion therapy. The first randomized trial (n = 533) to establish the benefits of early reperfusion, the Netherlands Randomized Trial, achieved infarct vessel patency in 85% of patients within 200 minutes of symptom onset by administering intracoronary streptokinase alone or following a rapid intravenous infusion of streptokinase. Ejection fraction improved significantly and mortality at 28 days was reduced (6% vs 12%). The ISIS‐2 Trial (1988) showed mortality reduction with intravenous thrombolytic therapy up to 24 hours after infarct onset, but did not explain the benefit of late reperfusion. In the Second Mt. Sinai‐N.Y.U. Reperfusion Trial (1989; n = 393), intracoronary streptokinase administered 4 to 14 hours after infarct onset increased thallium uptake. Streptokinase improved ejection fraction in patients with collateralized total occlusion but not in those with noncollateralized total occlusion. Preintervention antegrade flow was associated with ejection fraction improvement regardless of treatment assignment. We concluded that thrombolytic therapy after > 4 hours of infarction salvages myocardium in patients with collateralized total coronary artery occlusion. Total coronary occlusion was associated with collateral flow in 33% at acute angiography, but in 90% at day 10 to 14 angiography, indicating a second phase of collateral growth. An angioplasty model was developed to assess appearance and disappearance of collateral flow immediately after controlled coronary occlusion and reflow in humans. Using this model we demonstrated limitation of ischemia by collateral recruitment prospectively.

Coronary Thrombolysis

The clinical description of acute myocardial infarction (AMI) by Herrick 1 Herrick JB. Clinical features of sudden obstruction of the coronary arteries. JAMA. 1912; 59: 2015-2020 Crossref Google Scholar in 1912 embodied the concept that acute coronary thrombosis was responsible, and this view was widely adopted. The first trial of IV administration of thrombolytic therapy was published in 1959 2 Fletcher AP Sherry S Alkjaersig N et al. The maintenance of a sustained thrombolytic state in man: II. Clinical observations on patients with myocardial infarction and other thromboembolic disorders. J Clin Invest. 1959; 38: 11-19 Google Scholar and the first of intracoronary use was published in I960. 3 Boucek HJ Murphy WP. Segmental perfusion of the coronary arteries with fibrinolysin in man following a myocardial infarction. Am J Cardiol. 1960; 5: 525-533 Abstract Full Text PDF Google Scholar Over the next 25 years, 24 randomized studies of IV thrombolytic therapy were conducted, primarily in Europe, 4 Yusuf S Collins R Peto R et al. Intravenous and intracoronary fibrinolytic therapy in acute myocardial infarction: overview of results on mortality, reinfarction and side effects from 33 randomized controlled trials. Eur Heart J. 1985; 6: 556-585 PubMed Google Scholar the results varying from statistically significant benefit to no suggestion of benefit, and thrombolytic therapy was rarely used. In the late 1970s, there was a reawakening of interest in thrombolytic therapy for AMI, initially directed at intracoronary administration. 5 Chazov EL Mateeva LS Mazaer AV et al. Intracoronary administration of fibrinolysis in acute myocardial infarction. Ter Arkh. 1976; 48: 8-19 PubMed Google Scholar ,6 Rentrop KP Blanke H Karsch KR et al. Selective intracoronary thrombolysis in acute myocardial infarction and unstable angina pectoris. Circulation. 1981; 63: 307 Crossref PubMed Google Scholar The reality that most hospitals do not have cardiac catheterization laboratories and the recognition of the economic and logistic impediments to emergency cardiac catheterization, even in referral hospitals, stimulated a reevaluation of IV thrombolytic therapy. 7 Schroeder R Biamino G Leitner E-R et al. Intravenous short-term infusion of streptokinase in acute myocardial infarction. Circulation. 1983; 67: 536-548 Crossref PubMed Google Scholar ,8 Lo YSA. Intravenous versus intracoronary streptokinase in acute myocardial infarction. Clin Cardiol. 1985; 8: 609-619 Crossref PubMed Google Scholar

Comparative immunogenicity and thrombolytic properties toward arterial and venous thrombi of streptokinase and recombinant staphylokinase in baboons.

Streptokinase is a routinely used thrombolytic agent that is immunogenic and relatively inefficient toward platelet-rich thrombus, whereas staphylokinase is a poorly studied fibrinolytic agent. Here, the comparative immunogenicity and thrombolytic properties toward arterial platelet-rich thrombus and venous whole blood clots of streptokinase and recombinant staphylokinase were studied in baboons. The inhibitory capacity of baboon plasma (in a human plasma-based clot lysis assay) was 0.39 +/- 0.25 microgram streptokinase and 0.04 +/- 0.05 microgram recombinant staphylokinase per milliliter of plasma (mean +/- SD, n = 9). Intravenous infusion over 1 hour of 0.300 mg/kg of streptokinase at 0, 1, 2, 3, and 5 weeks in five baboons given heparin and the antiplatelet agent ridogrel increased the streptokinase-neutralizing titer from 0.22 +/- 0.18 microgram/mL plasma at baseline to 3.8 +/- 4.4 micrograms/mL after 2 weeks (p = 0.043 versus baseline by Wilcoxon signed rank test) and to 4.4 +/- 4.6 micrograms/mL after 5 weeks, whereas the thrombolytic potency toward a 125I-fibrin-labeled plasma clot inserted into an extracorporeal arteriovenous loop was reduced from 84 +/- 7% at baseline to 45 +/- 8% after 2 weeks and to 36 +/- 8% after 5 weeks (p < 0.01 versus baseline). Administration over 1 hour of 0.065 mg/kg recombinant staphylokinase at 0, 1, 2, 3, and 5 weeks in four baboons did not induce measurable staphylokinase-neutralizing activity in three of the four animals after 5 weeks. In the fourth baboon, a staphylokinase-neutralizing activity of 0.8 and 1.5 micrograms/mL was found at 3 and 5 weeks, respectively. Repeated staphylokinase administration was not associated with inhibition of clot lysis (43 +/- 4% lysis at baseline, 52 +/- 9% at 3 weeks, and 61 +/- 14% at 5 weeks; p = NS versus baseline). Repeated administration of streptokinase but not of staphylokinase caused a marked (> 50%) decrease in blood pressure, requiring administration of steroids and intravenous fluids, and a marked increase in leukocyte count and hemoglobin concentration. Intravenous infusion of streptokinase or recombinant staphylokinase over 1 hour in doses ranging between 0 and 1.0 mg/kg in three groups of four baboons each induced dose-dependent lysis of a 125I-fibrin-labeled autologous jugular vein blood clot (50% lysis requiring 0.140 mg/kg streptokinase and 0.058 mg/kg recombinant staphylokinase, representing equimolar amounts of 3.25 nmol/kg) without systemic fibrinogen depletion. The thrombolytic potency toward platelet-rich arterial thrombus of streptokinase and recombinant staphylokinase were studied in a femoral arterial eversion graft model. Arterial recanalization with recombinant staphylokinase was more frequent and more persistent than with streptokinase (all p < 0.05). Intravenous infusion of 1.0 mg/kg streptokinase or 0.25 mg/kg recombinant staphylokinase in two groups of four baboons each given intravenous heparin (200-unit bolus and 50 units.kg-1 x hr-1) and aspirin (10 mg/kg) did not produce a significant prolongation of the median template bleeding time. Recombinant staphylokinase has a thrombolytic potency toward jugular vein blood clots in baboons comparable to that of streptokinase, but it is less immunogenic and less allergenic and it does not induce resistance to lysis upon repeated administration; it is significantly more efficient than streptokinase for the dissolution of platelet-rich arterial eversion graft thrombi. Recombinant staphylokinase, which can be easily obtained in active form by expression in Escherichia coli, may constitute a potentially useful alternative to streptokinase for the treatment of acute myocardial infarction.

Comparison of results of intravenous infusion of anistreplase versus streptokinase in acute myocardial infarction

This randomized study compares the coronary perfusion rate in patients with acute myocardial infarction (AMI) treated with 2 different intravenous thrombolytic agents: streptokinase 1.5 million U given over 60 minutes and anisoylated human plasminogen streptokinase activator complex (anistreplase) administrated as a bolus of 30 U over 5 minutes. One hundred seventy-five patients (149 men and 26 women, mean age 54 years) have been included in this study. Eightynine patients were treated with anistreplase and 86 patients with streptokinase. AMI was inferior in 54 patients (61%) in the anistreplase group and in 54 patients (63%) in the streptokinase group. It was anterior in 35 (40%) and 32 (37%) patients, respectively. Coronary angiography and ventriculography were performed at a mean time (± SEM) of 207 ± 11 minutes after the beginning of thrombolysis in 170 patients. A perfusion score grade of 2 or 3 according to the Thrombolysis in Myocardial Infarction trial was found in 63 patients (72%) in the anistreplase group and in 56 patients (68%) in the streptokinase group (p = MS). Severe bleeding occurred in 7 patients (8%) after anistreplase and in 6 patients (7%) after streptokinase. No cerebral hemorrhage occurred. Nine patients (5%) died during their hospital stay: 6 after anistreplase and 3 after streptokinase. It is concluded that intravenous administration of anistreplase or streptokinase is efficient and safe. Coronary patency 207 minutes after fibrinolysis, incidence of adverse events and mortality are similar in both groups.

Predictive value of ventricular arrhythmias for patency of the infarct-related coronary artery after thrombolytic therapy.

In animal studies reperfusion of coronary arteries is commonly accompanied by ventricular arrhythmias. It is not certain, however, whether ventricular arrhythmias can be used as a reliable non-invasive marker of reperfusion in humans. Two-channel Holter recordings were obtained from the start of an intravenous infusion of streptokinase until coronary angiography (2.8 (2.7) hours (mean SD)) afterwards) in 57 patients with acute myocardial infarction of less than four hours who were generally not treated with antiarrhythmic drugs. Ventricular arrhythmias occurred in 21 (37%) of the 57 patients: accelerated idioventricular rhythm in 13 patients and non-sustained ventricular tachycardia in 15 patients. Seven patients had both accelerated idioventricular rhythm and non-sustained ventricular tachycardia. Coronary angiography showed a patent infarct-related vessel in 12 (92%) of the 13 patients with accelerated idioventricular rhythm (95% confidence interval 66 to 99%), in 22 (50%) of the 44 patients without accelerated idioventricular rhythm (95% CI 34 to 66%), in 11 (73%) of the 15 patients with non-sustained ventricular tachycardia (95% CI 45 to 92%), and in 23 (55%) (95% CI 39 to 71%) of the 42 patients who did not have non-sustained ventricular tachycardia. Seventeen (81%) of the 21 patients with accelerated idioventricular rhythm, or non-sustained ventricular tachycardia, or both, had a patent infarct-related vessel (95% CI 58 to 94%) as did 17 (47%) of the 36 patients with no ventricular arrhythmia (95% CI 29 to 65%). In patients with accelerated idioventricular rhythm after thrombolysis the infarct-related vessel is almost certain to be patent; but the infarct-related coronary artery can still be patent when no arrhythmia is seen.

Comparative Fibrinolytic Properties of Staphylokinase and Streptokinase in Animal Models of Venous Thrombosis

The thrombolytic and pharmacokinetic properties of staphylokinase were compared with those of streptokinase in hamsters with a pulmonary embolus produced from human plasma or from hamster plasma, and in rabbits with a jugular vein blood clot produced from rabbit blood. In both models, a continuous intravenous infusion of staphylokinase and streptokinase over 60 min in hamsters or over 4 h in rabbits, induced dose-dependent progressive clot lysis in the absence of significant systemic activation of the fibrinolytic system. The results of thrombolytic potency (clot lysis at 30 min after the end of the infusion, in percent, versus dose administered, in mg/kg) were fitted with an exponentially transformed sigmoidal function (formula: see text) and the maximal percent clot lysis (c), the maximal rate of lysis (z = 1/4 ac.eb) and the dose at which the maximal rate of lysis is achieved (b) were determined. In hamsters with a pulmonary embolus produced from human plasma, streptokinase had a somewhat higher thrombolytic potency than staphylokinase, as revealed by a higher z value (2,100 +/- 1,100% lysis per mg/kg streptokinase administered versus 1,100 +/- 330% lysis per mg/kg for staphylokinase). In hamsters with a pulmonary embolus produced from hamster plasma, staphylokinase had a somewhat higher thrombolytic potency than streptokinase (z = 1,600 +/- 440 versus 1,200 +/- 370% lysis per mg/kg). Staphylokinase had a higher thrombolytic potency than streptokinase in rabbits,as revealed by a higher z-value (950 +/- 350% lysis per mg/kg staphylokinase administered versus 330 +/- 39% lysis per mg/kg for streptokinase) and a lower b-value (0.035 +/- 0.010 mg/kg staphylokinase versus 0.091 +/- 0.008 mg/kg for streptokinase.(ABSTRACT TRUNCATED AT 250 WORDS)

Intravenous Streptokinase

Streptokinase, the first of the thrombolytic agents to be used in acute myocardial infarction, has now been administered to many thousands of patients with this condition. Since early intervention and accessibility of care is paramount in these patients, intravenous infusion of streptokinase has largely replaced intracoronary use. Results of major trials (GISSI, ISIS-2 and ISAM) comparing streptokinase with standard treatment in more than 30,000 patients prove convincingly that intravenous streptokinase increases patient survival after myocardial infarction. The largest trial, ISIS-2, demonstrated a 23% reduction in 5-week vascular mortality after streptokinase use. The greatest benefits occur where streptokinase infusion is initiated early after symptom onset, although late benefit has been observed in patients treated up to 24 hours after pain onset. Importantly, mortality is further decreased by combining streptokinase with aspirin, as shown by a 53% reduction in mortality using the combination in the ISIS-2 trial. Mortality has also been reduced in trials investigating the use of the thrombolytic agents rt-PA and anistreplase. Streptokinase and rt-PA produced similar reductions in mortality in the recent GISSI-2 and International t-PA/Streptokinase Mortality trials, findings which may be further clarified by ongoing comparative trials such as ISIS-3. Reperfusion of about 50 to 60% of occluded coronary arteries occurs with intravenous streptokinase, and left ventricular function is improved. Direct comparisons with rt-PA show a superior effect for the newer agent on early reperfusion, but a similar ability to salvage myocardial function. The complexities of the relationship between reperfusion, left ventricular function and mortality constitute an area of considerable clinical interest requiring further study to clearly differentiate between the drugs available to the physician. The most common adverse events observed during intravenous streptokinase infusion are bleeding complications. An incidence of 3.6% for minor bleeding and 0.4% for major haemorrhage (requiring transfusion) is derived from the combined results of the GISSI and ISIS-2 studies. Bleeding does not appear to be more frequent or severe with intravenous streptokinase than with the more fibrin-selective agent, rt-PA. While the risk to benefit ratio of sequential heparin following streptokinase therapy remains equivocal, the adjuvant use of aspirin confers a clinical advantage over streptokinase alone. In conclusion, streptokinase has now been proven to reduce mortality in patients with acute myocardial infarction, with an acceptable risk of bleeding complications. Given the substantial data that have now accumulated with extensive clinical experience, intravenous streptokinase should be considered a first-line agent in suitable patients.

Precordial ECG Mapping in Acute Myocardial Infarction (AMI) After Intravenous Infusion of Streptokinase (s)

Repeated precordial ECG mapping (42 leads) and CK-MB serum measurements were done in 40 patients with anterior and/or anterolateral acute myocardial infarction. Twenty patients serving as controls, were treated with routine anticoagulant therapy. In 20 patients (the s group), randomly selected, a short-term IV infusion of 1,500,000 IU streptokinase was administered and followed by the same anticoagulant treatment as in controls. Ten subjects from each group underwent coronary arteriography one month later. From the analysis of ECG mapping the number of leads (N) and the sum of measurements (sigma) for each parameter were calculated. Before treatment there were no significant differences for all measured parameters between the two groups of patients. Seven days later, ST elevations were statistically different for NST and sigma ST with lower values for the s group. Higher values for NR and sigma R were also noted in this group. No statistically significant difference was found for NQ and sigma Q. CK-MB curve showed an earlier peak in the s group than in the control group. Five patients from the s group showed a patency of the infarct-related vessel. In conclusion, the results of this study show that patients receiving s have a significant benefit with ECG improvement. On the other hand, the CK-MB curve indicates an eventual recanalization to a certain degree in the obstructed coronary artery, which is the final goal.

Short-term infarct vessel patency with aspirin and dipyridarnole started 24 to 36 hours after intravenous streptokinase

The duration of intravenous heparin therapy required to maintain patency of the infarct-related artery after intravenous streptokinase is uncertain. Twenty-eight patients were prospectively treated with 1.5 million unite of intravenous streptokinase within 4 hours of onset of chest pain. Intravenous heparin was begun after the streptokinase infusion was complete and was discontinued within 36 hours. Aspirin, 325 mg daily, and dipyridamole, 75 mg three times a day, was begun before the heparin was discontinued. Coronary angiography was performed both at 2 hours after completion of the streptokinase infusion and again at a mean of 8.7 (± 3.2) days after the initial catheterization. One patient died after treatment with streptokinase but before early angiography. In 21 of 27 patients (78%), Thrombolysis in Myocardial Infarction trial (TIMI) grade 2 or 3 perfusion in the infarct vessel was observed on initial angiography. Repeat angiograms were available in 17 of the 21 patients with initially patent vessels. Continued patency (TIMI grade 2 or 3) was found in 15 of the 17 patients (88%). Two of the four patients who did not undergo repeat angiography died, and the remaining two patients required coronary artery bypass grafting for unstable angina. Bleeding complications occurred in 6 of 27 patients (22%), with two (7%) requiring surgical evacuation of a groin hematoma. There were no instances of intracerebral bleeding and only two patients required transfusions. Thus, the combination of aspirin and dipyridamole following 36 hours of systemic heparinization after intravenous streptokinase infusion is associated with a reocclusion rate comparable to that which has been reported for more prolonged systemic anticoagulation with fewer hemorrhagic complications.

Streptokinase Lysis of Arterial Thrombus Threatening Renal Allograft — A Case Report

This case report describes a diabetic patient with an arterial thrombus lo cated in the common iliac artery, just proximal to the takeoff of the renal artery to a transplanted kidney. The clinical problem was how to preserve both lower extremity perfusion and allograft function while lysing the thrombus. Thera peutic options considered were: (1) blind femoral thrombectomy using a Fo garty Catheter, (2) renal artery isolation and open thrombectomy, (3) selective intraarterial streptokinase infusion, and (4) systemic intravenous streptokinase infusion. The fourth option was chosen and resulted in complete dissolution of the thrombus while avoiding further distal embolization and renal transplant infarction.

The typical staccato phenomenon of myoglobin in acute myocardial infarction disappears under thrombolytic treatment

Myoglobinemia in acute myocardial infarction (AMI) shows atypical profile in its time course. Multiple peaks are noted during the early phase of AMI, which is called ‘staccato phenomenon’. We observed that this phenomenon changed under thrombolytic treatment (streptokinase, 500 000 to 1000 000 IU as a single dose i.v.) within the first 4 h after onset of symptoms. Out of a group of 22 patients (8 control subjects), 14 received intravenous short term infusion of streptokinase. Six of them showed 1 peak (298.33 ± 23.58 min after onset of symptoms), six showed 2 peaks (after 192 ± 17.72 and 220.2 ± 63.84 min), one streptokinase patient died during the investigation, one showed 4 peaks in the myoglobin curve and, remarkably, also 3 peaks in the CK-time course. In the control group we observed 3–4 peaks in the myoglobin curve. Myoglobin was assessed by use of radioimmunoassay. Our findings indicate a possible relation between the presence of a thrombus and the discontinuity of myoglobin release. Successful reperfusion is reflected in the disappearance of the typical staccato phenomenon.

Randomized factorial trial of high-dose intravenous streptokinase, of oral aspirin and of intravenous heparin in acute myocardial infarction

619 patients with suspected acute myocardial infarction (MI) were randomized to receive either a high-dose short-term intravenous infusion of streptokinase (1.5 MU over one hour) or placebo. Using a '2 × 2 × 2 factorial' design, patients were also randomized to receive either oral aspirin (325 mg on alternate days for 28 days) or placebo and separately randomized to receive either intravenous heparin (1000 1U h-1 for 48 hours) or no heparin. Streptokinase (SK) was associated with a nonsignificant (NS) increase in non-fatal reinfarc–tion (3.9% SKvs 2.9% placebo) and decrease in mortality (7.5%vs9.7% in hospital plus 6.1%vs 8.7% after discharge). After SK, there were significantly fewer strokes (0.5% vs 2.4%; 2P<0.05), but significantly more minor adverse events (e.g. hypotension and bradycardial, allergies, bruises or minor bleeds, nausea). Aspirin was associated with fewer non-fatal reinfarctions (3.2% aspirin vs 39% placebo; NS), deaths (in hospital: 61% vs 10.5%; 2P<0.05, and after discharge: 7.0% vs 6.9%; NS), and strokes (0.3% vs 2.0%; NS). Heparin was associated with a decrease in reinfarction (2.2% heparin vs 4.9% no heparin; NS), though not in mortality (in hospital: 8.0% vs 8.5%; NS, and after discharge: 7.0% vs 6.9%; NS), and with a trend towards more strokes (1.6% vs 0.7%; NS) and more bruising and bleeding (14% vs 12%; NS). To assess more reliability the effects of aspirin and of this SK regimen on mortality, about 400 hospitals worldwide are now collaborating in a large (about 20 000 patients planned ) randomized trial ( ISIS-2). for which the present study was a pilot.

Fibrinolytic therapy for femoral arterial thrombosis after cardiac catheterization in infants and children

The charts of 79 patients who required femoral arterial (FA) thrombectomy after cardiac catheterization were reviewed. Fifteen patients (19%) had poor pulses after thrombectomy and 2 had an extremity amputated. One thousand consecutive patients undergoing cardiac catheterization were also studied to prospectively determine the safety and efficacy of systemic fibrinolytic therapy for treatment of FA thrombosis. Among these, 771 patients underwent retrograde arterial catheterization, including 31 patients with left-sided obstructive lesions who had undergone transarterial balloon dilation procedures with large catheters. All patients were given heparin at the time of arterial cannulation. Patients who had a pulseless extremity 4 hours after catheterization continued to receive heparin therapy for 24 to 48 hours. If the extremity continued to have no palpable pulse and the systolic blood pressure was less than 50% of that in the contralateral leg, intravenous streptokinase infusion was begun. The overall incidence of FA thrombosis was 3.6% (28 of 771), including 39% (12 of 31) of all patients undergoing transarterial balloon dilation procedures; 97% (27 of 28) of patients weighed less than 14 kg and the majority weighed less than 10 kg. After an average treatment period of 33 hours, 16 patients continued to have a pulseless extremity and were treated with streptokinase for an average duration of 13 hours. Normal pulses and systolic blood pressure returned in 14 (88%) and were nearly normal in 1 other patient (6%). The incidence of bleeding at the arterial puncture site was 25% and was highest in the patients who had a transarterial balloon dilation procedure. No serious complications occurred.

High-dose, brief-duration intravenous infusion of streptokinase in acute myocardial infarction: Description of effects in the circulation

The effects in the circulating blood of a 1-hour intravenous infusion of 1.5 × 10 6 units of streptokinase (SK) were measured during the subsequent 24-hour period in 7 patients with acute myocardial infarction. At the end of the infusion, the activator activity, expressed in SK units, averaged 65 U/ml, all of the plasminogen had disappeared, only a small amount of free plasmin was still present and functionally active α 2 antiplasmin had been reduced to 21% of the preinfusion level. All of the native fibrinogen had been degraded and the thrombin-coagulable protein was composed entirely of fragment X species, but the circulating plasma also contained significant amounts of the more extensively degraded fragments Y, D and E. The biologic half-life of the SK-induced activator activity was 23 minutes and that of the fibrinogen degradation products was 6.3 hours. The lytic effects persisted for 4 hours before any signs of recovery from the hemostatic defect were evident; considerable recovery was present at 25 hours.

Combined Intravenous and Intracoronary Thrombolysis in Acute Transmural Myocardial Infarction

The effect of intravenous infusion of streptokinase (SK) (16 700 U min−1 for 90 min) started after diagnosis and followed by intracoronary administration (2000 U min−1) was assessed retrospectively in 55 consecutive patients with acute transmural myocardial infarction (MI). Another 46 patients with acute MI treated previously by intracoronary thrombolysis alone served as controls. Reperfusion at first coronary injection was observed after pretreatment with intravenous SK in 25 patients (45%) but in no control patient (P <0·001). Fifteen patients with successful pretreatment (group A), 20 patients with successful intracoronary thrombolysis alone (group B), and 9 patients with unsuccessful thrombolysis (group C) were restudied after 4 weeks. Data of patients with reinfarction, coronary bypass surgery, or percutaneous transluminal coronary angioplasty before restudy were excluded. Thallium-201 scintigraphy was performed before and 24 h after treatment, serum creatine kinase activity was measured every 8 h for 3 days, and regional ejection fraction (EF) of acute MI was determined before and 4 weeks after treatment. The scintigraphic, enzymatic and haemodynamic data before treatment indicated severe and comparable ischaemia in the three groups. The thallium-201 scintigraphy showed a tendency to a more marked reduction of the perfusion defect in group A than in groups B and C. Peak serum CK activity normalised by the perfusion area of infarct vessel was significantly lower in group A than in group C. Regional EF of acute infarcted area recovered more after 4 weeks in group A than in both other groups. Time to catheterisation from onset of symptoms was similar among the three groups; start of treatment and angiographic proof of reperfusion, however, were achieved earlier in group A than in group B. Thus, successful treatment with the combination of intravenous and intracoronary thrombolysis is effective in limiting infarct size by reducing the time of ischaemia.

The hypotensive effect of intravenous streptokinase in patients with acute myocardial infarction.

We studied the hypotensive effect of a rapid intravenous infusion of high-dose streptokinase in 98 patients with an acute myocardial infarction. The systolic blood pressure fell from 132 +/- 20 (range 90 to 174) to 97 +/- 21 mm Hg (range 58 to 152) at 15 +/- 8 min (range 4 to 40) after the commencement of the streptokinase infusion (p less than .001). A fall in diastolic blood pressure from 80 +/- 16 (range 51 to 105) to 61 +/- 15 mm Hg (range 32 to 92) accompanied the fall in systolic pressure (p less than .001). The fall in blood pressure was associated with an increase in heart rate (73 +/- 14 to 78 +/- 17 beats/min, p less than .001), preceded the appearance of clinical signs of reperfusion by 37 +/- 38 min and was similar in magnitude and timing in patients with anterior and inferior infarction. There were direct relationships between the rate of infusion of streptokinase and both the magnitude (r = .49, p less than .001) and the rate of fall of systolic blood pressure (r = .67, p less than .001) as well as both the magnitude and rate of fall of diastolic blood pressure. In most patients, the fall in blood pressure was transient (9 +/- 6 min, range = 2 to 30) and easily managed by slowing or stopping the infusion, placing the patient in the Trendelenburg position, or by administering an infusion of low-dose norepinephrine or dopamine. However, in four patients with severe left ventricular dysfunction, severe hypotension persisted for more than 60 min.(ABSTRACT TRUNCATED AT 250 WORDS)