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The role of intravenous streptokinase in acute arterial occlusions after cardiac catheterization.

Arterial occlusions after cardiac catheterization are usually treated surgically. We report four patients with femoral thrombosis or distal emboli that developed after cardiac catheterization. Each patient was treated successfully with intravenous streptokinase. Therapy was initiated 1-60 hr after the procedure. The duration of infusion lasted 4-42 hr (mean 27 hr). Pulses were restored 4-19 hr (mean 10 hr) after the beginning of infusion. There was no major hemorrhagic complication, even in patients with very early streptokinase infusion. Thus intravenous streptokinase may be an alternate choice to surgery for arterial occlusions after invasive procedures.

Adult↗

Intracoronary streptokinase therapy in the coronary care unit for acute myocardial infarction.

Intracoronary streptokinase was offered and preliminary coronary angiography performed in 14 patients who were seen with the clinical diagnosis of acute myocardial infarction within 4 h of onset of symptoms. The procedure was performed in the Coronary Care Unit (CCU) of St. Peter's Medical Center with the use of a portable C-arm fluoroscope. Angiography was recorded on video tape. Service was provided by an "on-call" team consisting of two physicians, a CCU nurse, and a radiology technician, on a 24-h service basis. Adequate visualization of coronary anatomy was obtained in all patients. Patency of occluded vessels was achieved in 10 of 11 patients who received intracoronary streptokinase. The initial streptokinase bolus was administered at a mean interval of 4.1 h from onset of symptoms. It is concluded that speedy and effective coronary thrombolytic therapy can be provided in the CCU on a 24-h service basis by an on-call team. The use of CCU for this purpose will make this therapy widely available across the country, without the need for Cardiac Catheterization Laboratory.

Adult↗

Intravenous versus intracoronary streptokinase in acute myocardial infarction.

Nine studies specifically dealing with the comparison of intravenous streptokinase (IVSK) and intracoronary streptokinase (ICSK) in the treatment of acute myocardial infarction (MI) were analyzed to determine if IVSK is as efficacious as ICSK in achieving thrombolysis. Pooled data from the studies yielded success rates of 73% for IVSK and 72% for ICSK. Considering that the studies which did not perform preintervention angiogram may have overestimated the thrombolytic success rate in IVSK patients, there is a possibility that ICSK may be slightly more effective in achieving acute reperfusion. Bleeding complications were similar, and a systemic lytic state was observed in both treatment groups. No definitive conclusions can be drawn regarding the differences between groups in improvements of left ventricular function and mortality rates. ICSK has the advantage of direct documentation of reperfusion and spares the patient the risk of anticoagulation should the attempt fail. On the other hand, IVSK is cheaper, easier to administer, and can logistically be given earlier (even in the emergency room or ambulance) than ICSK; it is therefore more widely available, and may be the preferred mode of treatment in community hospitals where cardiac catheterization facilities are not readily available, if streptokinase is to be given at all.

Cardiac Output↗

Cost and efficacy of intravenous streptokinase plus PTCA for acute myocardial infarction when therapy is initiated in community hospitals.

The costs and clinical results of a thrombolytic therapy protocol using intravenous (IV) streptokinase in small community hospitals prior to emergency transfer for cardiac catheterization for possible percutaneous transluminal coronary angioplasty (PTCA) were prospectively studied in 56 patients with an acute myocardial infarction [Tulsa Heart Center-Myocardial Infarction Study Team (THC-MIST) protocol]. Findings were compared to those for 53 similar patients receiving "conventional therapy" during the same study period. The reperfusion rate for IV streptokinase was 63%. Additional emergency PTCA yielded a total reperfusion rate of 95%. Despite emergency cardiac catheterization for all THC-MIST patients, average hospital charges were not significantly different between the two groups ($20,495 vs. $20,722; THC-MIST vs. conventional therapy, respectively). Total charges (hospital plus physician fees) were also not significantly different ($22,986 vs. $22,400; THC-MIST vs. conventional therapy, respectively). Intensive care unit (ICU) days and total hospital stays were significantly less for THC-MIST patients (3.1 vs. 5.8 ICU days, p less than 0.05 and 8.8 vs. 12.4 hospital days, p less than 0.05; THC-MIST vs. conventional therapy, respectively). Thus initiation of IV streptokinase in community hospitals for acute myocardial infarction with subsequent transfer for possible PTCA can yield high reperfusion rates without significantly increasing health care costs.

Adult↗

Tolerance and complications in a multicenter trial of intravenous APSAC and intracoronary streptokinase in acute myocardial infarction.

Adverse events data of a randomized, multicenter, angiographically controlled trial of intracoronary streptokinase and intravenous anistreplase, or anisoylated plasminogen streptokinase activator complex (APSAC) are presented. The frequency of severe adverse events is similar for streptokinase and anistreplase; no unexpected adverse experiences were reported with either drug. The most frequently encountered side effect was bleeding, overwhelmingly from the groin puncture site from angiography.

Acute Disease↗

Variability of thrombolytic coronary reperfusion: an angiographic study of streptokinase and anistreplase.

A total of 1,615 angiographic readings in 240 patients with acute myocardial infarction were analyzed from a randomized trial of intravenous anistreplase (Eminase), also known as anisoylated plasminogen streptokinase activator complex (APSAC), versus intracoronary streptokinase. Coronary arteriography was performed at baseline and at 15, 30, 45, 60, 75, and 90 minutes after drug infusion. Coronary flow in the infarct-related artery was defined using the TIMI criteria. Some serial change in perfusion was noted in 25% of the total patient population and in 49% of all reperfusion patients. Complete loss of perfusion (grade 2 or 3 to grade 0 or 1) occurred in 35% of all reperfused patients. Half of these patients ultimately developed complete loss of perfusion at the study endpoint. All of these changes in flow were statistically more common for the circumflex coronary artery and early treatment (less than 4 h), but did not differ for anistreplase or streptokinase. We conclude that frequent alterations in coronary blood flow occur early during reperfusion therapy and that these findings may explain reports with varying results of thrombolytic therapy. Any angiographic assessment of thrombolytic drug efficacy should take these variations as well as interobserver variability into account.

Adult↗

Specificity role of the streptokinase C-terminal domain in plasminogen activation.

Several pathogenic bacteria secrete plasminogen activator proteins. Streptokinase (SKe) produced by Streptococcus equisimilis and staphylokinase secreted from Staphylococcus aureus are human plasminogen activators and streptokinase (SKu), produced by Streptococcus uberis, is a bovine plasminogen activator. Thus, the fusion proteins among these activators can explain the function of each domain of SKe. Replacement of the SKalpha domain with staphylokinase donated the staphylokinase-like activation activity to SKe, and the SKbetagamma domain played a role of nonproteolytic activation of plasminogen. Recombinant SKu also activated human plasminogen by staphylokinase-like activation mode. Because SKu has homology with SKe, the bovine plasminogen activation activities of SKe fragments were checked. SKebetagamma among them had activation activity with bovine plasminogen. This means that the C-terminal domain (gamma-domain) of streptokinase determines plasminogen species necessary for activation and converses the ability of substrate recognition to human species.

Animals↗

Comparison of human VDAC1 with streptococcal streptokinase and bovine bactericidal permeability increasing protein: role of structural information in identifying functionally significant domains.

Comparison of the primary amino acid sequence of the human X-linked voltage-dependent anion channel, with other sequences in data base searches, identified regions of similarity in streptococcal streptokinase and bovine bactericidal permeability increasing protein. These regions of similarity were in different areas of the protein and were relatively short. However, examination of an empirically derived structural model of the channel showed that each region of similarity in streptokinase and bovine bactericidal permeability increasing protein corresponded to contiguous transmembrane domains within the channel protein. We speculate that these transmembrane domains may be functionally significant for streptokinase and bovine bactericidal permeability increasing protein. These investigations demonstrate the need for incorporation of information regarding secondary, tertiary, and quaternary structures, as well as function, in algorithms used for database searches.

Amino Acid Sequence↗

Intravenous streptokinase therapy in acute myocardial infarction: assessment of therapy effects by quantitative 201Tl myocardial imaging (including SPECT) and radionuclide ventriculography.

To evaluate a potential beneficial effect of systemic streptokinase therapy in acute myocardial infarction, 36 patients treated with streptokinase intravenously were assessed by radionuclide ventriculography and quantitative 201Tl myocardial imaging (including SPECT) in comparison with 18 conventionally treated patients. Patients after thrombolysis had significantly higher EF, PFR, and PER as well as fewer wall motion abnormalities compared with controls. These differences were also observed in the subset of patients with anterior wall infarction (AMI), but not in patients with inferior wall infarction (IMI). Quantitative 201Tl imaging demonstrated significantly smaller percent myocardial defects and fewer pathological stress segments in patients with thrombolysis compared with controls. The same differences were also found in both AMI and IMI patients. Our data suggest a favorable effect of intravenous streptokinase on recovery of left ventricular function and myocardial salvage. Radionuclide ventriculography and quantitative 201Tl myocardial imaging seem to be reliable tools for objective assessment of therapy effects.

Adult↗

Cleansing properties of stabilized trypsin and streptokinase-streptodornase in necrotic leg ulcers.

The cleansing effects on pus and debris of streptokinase-streptodornase and of stabilized crystalline trypsin were compared in 40 patients (12 males, 28 females) with necrotic varicose or arteriosclerotic leg ulcers. Both preparations produced significant partial or total cleansing of the ulcers of necrotic material, and both enhanced the granulation and epithelialization of most of the ulcers. Streptokinase-streptodornase was significantly more effective in removing freshly formed damp and smearing pus and debris. Neither preparation prevented the formation of or removed very deep adherent necrotic areas, especially in arteriosclerotic leg ulcers. Trypsin caused significantly more pain than streptokinase-streptodornase during the treatment period and on changing dressings. Both enzymes indirectly reduced the bacterial flora of the ulcers, probably by removal of necrotic wet material.

Aged↗

[Influence of a streptokinase-induced fibrinolysis on the extent of the acute experimental myocardial infarction (author's transl)].

In 17 unaesthetized dogs several side branches of the left descending coronary artery were ligated. The ST-segment elevation in the epicardial ECG ascended to 22 mV after 5 min and to 19 mV after 20 min. Aortic pressure, left ventricular enddiastolic pressure, heart rate and hemostasiological parameters (thrombin-time, thrombin-coagulase-time, reptilase-time, plasma-fibrinogen, staphylococcal clumping test) did not change significantly. 20 min after the beginning of coronary occlusion, the vessels were reopened. When ST-segment elevation had disappeared, a controlled fibrinolytic therapy (Streptokinase 1.5 Mega I.E. in 30 min, later on 0.75 Mega I.E./h) was induced. When an effective fibrinolysis could be demonstrated by the hemostasiological parameters, the same vessels were occluded again. Now the hemodynamic parameters too did not change significantly, but the ST-segment elevation was significantly diminished for more than 50% compared with simple ligation. A control group, which only got the solvent of the streptokinase, showed the same ST-segment elevation. This effect, induced by streptokinase is ascribed to fibrinogen degradation products and a diminution in the amount of fibrinogen which cause an improvement of microcirculation.

Animals↗

Thrombolysis with streptokinase during cardiopulmonary resuscitation: a single center experience and review of the literature.

OBJECTIVE: To report our experience with use of thrombolysis with streptokinase during cardiopulmonary resuscitation of patients with cardiac arrest due to myocardial infarction. DESIGN: A case series. METHODS: Thrombolytic therapy (streptokinase) was administered during cardiopulmonary resuscitation of 4 patients with suspected myocardial infarction as the cause of cardiac arrest. RESULTS: 3 of the 4 patients survived and were discharged from the hospital without any major complications or neurological sequela. CONCLUSION: Thrombolysis with streptokinase during cardiopulmonary resuscitation of patients with suspected acute myocardial infarction is associated with reduced mortality and favorable neurological outcome.

Adult↗

Exercise-induced ischemia in the streptokinase-reperfused myocardium: relationship to extent of salvaged myocardium and degree of residual coronary stenosis.

To assess the functional significance of residual stenosis at the site of the thrombolysed infarct-related coronary artery, 37 patients underwent exercise radionuclide ventriculography or stress-redistribution thallium-201 scintigraphy at an average of 7 weeks following streptokinase therapy during evolving myocardial infarction. The size of the initially jeopardized myocardium and the salvaged myocardium were quantitated on thallium-201 studies obtained immediately before and 10 days after streptokinase infusion. Exercise-induced ischemia (defined by reversible thallium-201 perfusion defects or stress-induced deterioration of regional wall motion) in the reperfused myocardium was absent in 46% of patients and was present in different degrees in the remaining 54%. A significantly lower proportion of patients, however, showed exercise-induced chest pain and/or ST segment depression (10% and 20%, respectively). By stepwise multiple logistic regression analysis, the quantitatively determined size of the salvaged myocardium (398 units versus 65 units, p less than 0.01) and the ratio of the salvaged myocardium/extent of initially jeopardized myocardium (70% versus 28%, p less than 0.01) were both independent predictors of stress-induced ischemia, whereas the extent of initially jeopardized myocardium (585 units versus 407 units, p = NS), incidence of greater than or equal to 99% coronary stenosis (37% versus 46%, p = NS), and ischemic time (160 versus 196 minutes, p = NS) did not provide additional predictive information. We conclude that exercise-induced ischemia, which is frequently present in the streptokinase-reperfused myocardium, cannot be detected accurately by exercise-induced chest pain or ST segment depression, nor can it be predicted by the severity of residual coronary stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Emergency room infusion of intravenous streptokinase in acute myocardial infarction: feasibility, safety, and hemodynamic consequences.

Between September 1, 1986, and December 31, 1987, sixty-four consecutive patients younger than 70 years, with early (less than 4 hours) symptoms and signs of myocardial infarction, were treated with 1.5 million units streptokinase intravenously in the emergency room (ER group) before admission to the coronary care unit. Data from these patients were compared in retrospect to those of 66 consecutive patients with myocardial infarction who were treated with intravenous streptokinase in the coronary care unit (CCU group) before September 1, 1986. Time between first symptoms and initiation of fibrinolytic therapy was significantly shorter in the ER group: 114 +/- 53 minutes vs 150 +/- 56 minutes in the CCU group (p less than 0.001). The incidence of in-hospital complications was similar in both groups. However, left ventricular stroke work index during the stay in the coronary care unit was 50 +/- 19 gm/m2 in the ER group vs 42 +/- 14 in the CCU group (p = 0.02). Also the echocardiographic left ventricular wall motion score at 48 hours after admission tended to be better in the ER group: 6.7 +/- 4.0 compared to that in the CCU group (7.6 +/- 4.5; p = 0.29). In conclusion, infusion of intravenous streptokinase in the emergency room is feasible and safe and results in a significant time gain leading to a better hemodynamic profile. Within the hospital the emergency room is the ideal place for intravenous fibrinolytic therapy in eligible patients with acute myocardial infarction.

Adult↗

Intravenous streptokinase in acute myocardial infarction at the community hospital: a six-year experience.

The efficacy of intravenous streptokinase in the initial management of acute myocardial infarction was evaluated over a 6-year period in 130 patients admitted to 3 community hospitals. Most patients were admitted within 2 hours of onset of symptoms and received 1.5 million units of streptokinase over a 30- to 60-minute period. Clinical observations and serial creatine phosphokinase-MB were indicative of vessel patency in 115 (88%) of the patients after initiation of thrombolysis. Of this group, 105 underwent catheterization, and recanalization was demonstrated in 97 (92%). Fifty percent of the patients who underwent reperfusion were subsequently maintained with medical therapy; 50% underwent either percutaneous transluminal coronary angioplasty or coronary artery bypass surgery. Major morbidity was confined to hematomas; no cerebral bleeding was encountered. There was 1 early death from cerebral thrombosis and 2 late deaths, 1 to cancer and 1 to myocardial infarction. These findings suggest the benefit of intravenous streptokinase thrombolysis in patients with acute myocardial infarction presenting within 3 hours of onset of pain, unless specific potential bleeding problems exist or in the case of certain very elderly persons. In addition, the trial demonstrated the feasibility of triaging patients who have undergone lytic therapy to a central facility for catheterization and management.

Adult↗

Partial resistance to anticoagulation after streptokinase treatment for acute myocardial infarction.

This study examines the response of 3 different groups of patients to anticoagulants: 50 patients previously treated with streptokinase for acute myocardial infarction (AMI) (group 1), 24 patients with AMI who had received anticoagulants without prior thrombolysis (group 2) and 11 subjects who received anticoagulants for noncoronary indications (group 3). No significant differences were detected between groups 2 and 3; therefore, they were combined for analysis. After streptokinase, patients required 37,755 +/- 1,516 (mean +/- standard error of the mean) U of heparin per day to achieve the desired activated partial thromboplastin time (APTT). The dosage was 30,294 +/- 1,089 U/day in patients without antecedent thrombolysis (p less than 0.001). Group 1 patients required 5 +/- 0.4 days until adequate anticoagulation was achieved, compared with 3 +/- 0.2 days in the control group (p = 0.01). Despite higher heparin requirements, group 1 patients had a lower APTT value than the other subjects (87 +/- 5 vs 101 +/- 6 seconds, p = 0.08). Group 1 patients required 5 +/- 0.3 days to reach anticoagulation with warfarin versus 4 +/- 0.2 days in groups 2 + 3 (p = 0.05). Comparison of groups 1 and 2 yielded similar, although smaller, differences. Patients treated with streptokinase for AMI seem to be partially resistant to anticoagulation, which may increase the risk of reocclusion.

Anticoagulants↗

Heparin and infarct coronary artery patency after streptokinase in acute myocardial infarction.

Anticoagulant therapy is frequently used after thrombolytic agents in the treatment of acute myocardial infarction (AMI) although it is unclear that such therapy will prevent subsequent infarct vessel reocclusion. The role of duration of heparin therapy in maintaining infarct artery patency was studied retrospectively in 53 consecutive AMI patients who received streptokinase therapy and underwent coronary angiography acutely and at 14 +/- 1 days. Of the 39 patients with initial infarct vessel patency, patency at follow-up angiography was observed in 100% (22 of 22) of those who received greater than or equal to 4 days of intravenous heparin but in only 59% (10 of 17) of those patients who received less than 4 days of heparin (p less than 0.05). Of the 14 patients not initially recanalized after streptokinase, patent infarct-related arteries at follow-up angiography were found in 3 of 8 (38%) treated with greater than or equal to 4 days of heparin therapy but in none of the 6 patients treated for less than 4 days (difference not significant). No significant difference in hemorrhagic complications was noted between the short- and long-term heparin treatment groups. Thus, greater than or equal to 4 days of intravenous heparin therapy after successful streptokinase therapy in AMI is more effective in maintaining short-term infarct vessel patency than a shorter duration of therapy and it may maintain the short-term patency of the infarct vessel in those patients who later spontaneously recanalize.

Angiography↗

Effects of early thrombolytic therapy (anistreplase versus streptokinase) on enzymatic and electrocardiographic infarct size in acute myocardial infarction. TEAM-2 Investigators.

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

Anistreplase↗