Fibrinolysin immobilized by a solid polysaccharide carrier capable of controllable biodegradation is shown to exert a local effective thrombolyzing action. Certain results of clinical studies of immobilized streptase (streptodecase) are presented. They show essential advantages of the new preparation over the known native enzymes. Experiments with animals show that the immobilized thrombin may be applied in therapeutic embolization for the hemorrhage cessation.
The Ontario Medical Association (OMA) guidelines for intravenous thrombolysis in acute myocardial infarction were released in March 1988 and contributed to a government decision against special per-case funding to assist hospitals using tissue-type plasminogen activator (tPA). In October 1988, 1512 cardiologists, internists and physician-administrators who were OMA members were mailed a questionnaire seeking their views on the OMA guidelines and related issues. Of the 419 questionnaires (28%) that were returned, 392 contained usable responses. Among the respondents 268 (68%) had used thrombolytic drugs in the preceding 12 months; the mean number of cases was 10.6 (standard deviation 12.9). A strong or a mild preference for tPA over streptokinase was registered by 64% of the respondents; 28% had no preference. However, the self-reported ratio of actual streptokinase:tPA use was about 3:1, and 73% indicated that the government's funding policy had limited the availability of tPA in their hospital. The respondents were almost equally divided as to whether the policy should be changed. The guidelines were deemed helpful by 85% of the noncardiologists, as opposed to 52% of the cardiologists (p less than 0.005). OMA involvement in developing and circulating such guidelines was supported by 74% of the respondents and opposed by 18%; opposition was more likely to come from those who found the guidelines unhelpful (p less than 0.001). Support for involvement by the College of Physicians and Surgeons of Ontario was much weaker (supported by 32%, opposed by 62%). Overwhelming opposition to government involvement was evident.
The usefulness of several different methods for detecting immune complex formation and complement activation in the circulation were applied to samples from patients receiving intravenous Streptokinase therapy for myocardial infarction. Streptokinase is a foreign antigen and can cause immune reactions. We collected samples from 13 patients, before Streptokinase administration (baseline), at the end of infusion (1 h), 12 h later and on day 7. We measured IgG containing immune complexes (IgG-IC), free C3d and antibodies to Streptokinase by ELISA, and CR1, C3d and C4d on erythrocytes by flow cytometric assay. Antibodies to Streptokinase are common, as all but two of the patients had measurable antibody levels. During Streptokinase treatment there was a drop in antibody levels, most prominent in those patients who had high baseline levels. At the same time increased levels of free C3d and erythrocyte-bound C3d were observed. After 12 h free C3d was usually back to baseline level, but C3d on erythrocytes was still raised. These data indicate the formation of Streptokinase immune complexes in patients with high Streptokinase antibody levels, and show that these complexes are cleared rapidly from the circulation, leaving more persistent signs of complement activation. We conclude that free C3d is a good indicator of ongoing complement activation, whereas C3d on erythrocytes indicates that complement activation has recently taken place.
Guidelines for the use of intravenous thrombolytic agents in acute myocardial infarction. Ontario Medical Association Consensus Group on Thrombolytic Therapy.
A consensus group convened under the auspices of the Ontario Medical Association produced guidelines for the use of intravenous thrombolytic agents in acute myocardial infarction. The guidelines, updated to December 1988, include the following points. 1) Any hospital that routinely accepts the responsibility for looking after patients with acute myocardial infarction could offer thrombolytic therapy if monitoring facilities are available and if the staff are experienced in the treatment of cardiac rhythm disturbances. 2) Before treatment, all patients must be carefully screened for factors predisposing to hemorrhagic complications. 3) A physician should be clearly designated as responsible for the care of the patient receiving an infusion and be available in the event of problems. 4) For the two approved agents the usual dosages are as follows: streptokinase, 1.5 million units given over 1 hour; and tissue-type plasminogen activator (tPA), 100 mg over 3 hours, delivered as 60 mg in the first hour (of which 6 to 7 mg should be given as a bolus in the first 1 to 2 minutes) and then an infusion of 20 mg/h over the next 2 hours. 5) Intravenous thrombolytics should be considered for any patient with presumed acute myocardial infarction, as suggested by prolonged chest pain or other appropriate symptoms and typical electrocardiographic changes. Expeditious treatment is critical, since myocardial necrosis occurs within hours. 6) Emergency angiography is indicated for patients with hemodynamic compromise and no apparent response to streptokinase or tPA and in those with recurrent chest pain suggestive of acute myocardial infarction despite an apparent response to intravenous thrombolysis. Angiography before discharge is recommended for patients with postinfarction angina or evidence from noninvasive testing of significant residual ischemic risk. 7) There is insufficient evidence to choose between streptokinase and tPA on the basis of the two most important outcome measures: patient survival and myocardial preservation. More conclusive evidence comparing tPA, streptokinase and another promising agent, acylated plasminogen-streptokinase activator complex, will be available in 1989-90.
Evidence of the potential impact of intravenous thrombolytic therapy on short-term revascularization rates among patients with acute myocardial infarction was sought. Because nonrandomized comparisons with conventional treatment would be subject to various confounders, a meta-analysis of randomized controlled trials was performed. Seven trials were included, applying standard doses of either tissue plasminogen activator or streptokinase without an aggressive revascularization protocol. Follow-up ranged from 14 to 30 days. The revascularization rates among treated patients in all trials were lower than in the conservative arm of the Thrombolysis in Myocardial Infarction Phase II trial, which established the current procedural benchmarks for postthrombolysis management. However, the aggregate volume of bypass surgery and angioplasty in patients treated with tissue plasminogen activator was more than double that of controls (odds ratio, 2.25; 95% confidence interval, 1.31 to 3.94), with a smaller but still significant increase for streptokinase-treated patients (odds ratio, 1.66; 95% confidence interval, 1.08 to 2.59). Combining all trials, the increase in mechanical revascularization was 80% (95% confidence interval, 33% to 144%). Thus, for patterns of practice currently accepted in North America, intravenous thrombolysis for myocardial infarction leads to a significant short-term increase in clinical and angiographic indications for revascularization as compared with conventional treatment.
The relationship between lytic state variables and ex vivo clot lysability was investigated in blood drawn from patients during streptokinase administration for acute myocardial infarction. A lytic state was already evident after 5 min of treatment and after 20 min the plasminogen concentration had decreased to 24%, antiplasmin to 7% and fibrinogen 0.2 g/l. Lysis of radiolabeled retracted clots in the patient plasmas decreased from 37 +/- 8% after 5 min to 21 +/- 8% at 10 min and was significantly lower (8 +/- 9%, p
In order to assess the impact of thrombolytic therapy on return to work 18 months after a first myocardial infarction 32 patients treated with streptokinase were compared to 30 patients not treated with streptokinase. The study was designed as a historical cohort study. The patients in both groups had continuous chest pain of less than six hours prior to admission and electrocardiographic changes consistent with acute myocardial infarction. The two groups were comparable with respect to medical variables related to their myocardial infarction and to educational level. A total of 17 patients (53%) in the streptokinase group and 16 (53%) among controls had stopped working 18 months after their MI. An association between the treatment and the working status could not be found (relative risk = 1.0) nor could it be found if the figures were corrected for deaths and retirements because of age. In conclusion, this study could not demonstrate any beneficial effect of thrombolytic therapy on the return to work 18 months after an initial myocardial infarction.
The streptokinase titrated initial dose (TID) was estimated in 31 2 patients consecutively admitted to a medical department in Oslo. 93% had a TID below 250,000 IU, 97% below 425,000 IU and 98.5% below 650,000 IU. No differences were found between the two sexes. The highest values were found in patients 50--60 years old. Otherwise, no differences were found between different age groups from 10 to 90 years of age. Two patients with extremely high TID values were both anamnestically prone to streptococcal infections. It is concluded that our standard initial dose of 250,000 IU of streptokinase is sufcient for the great majority of our patients. Pre-treatment test for TID is recommended only when recent streptococcal infections are suspected.
Since July 1994 the primary health care service in the municipality of Nordkapp has been conducting a study on the feasibility of prehospital thrombolytic treatment of acute myocardial infarction. The diagnosis of infarction was verified in all nine patients included in the study up until February 1998. In one patient the treatment was ended because of serious complications; in the other eight the treatment was without complications. There was a significant time saving for these patients compared to being given the same treatment in hospital. The authors argue that thrombolytic treatment of acute myocardial infarction should be defined in standard procedures and administered by general practitioners.
Increasing the period of myocardial ischaemia prior to conduction of reperfusion adequality induces complicated healing of experimental myocardial infarction, thereby resulting in postinfarctional aneurysm of the heart. Complicated healing of myocardial infarction upon of coronary blood re-circulation after 3 or more hours of ischaemia, happens due to disbalance of necrotic and reparative processes in the infarct zone. Conduction of reperfusion induces activation of necrotic processes with retention and slowdown of reparative processes.