The distribution of antibodies to streptokinase.

To determine the distribution of antibodies to streptokinase that might be anticipated in patients requiring treatment with streptokinase, specific anti-streptokinase antibody titres were determined in a group of subjects from the general population and in a group of patients presenting with acute myocardial infarction. Enzyme-linked immunosorbent assays were developed to measure specific anti-streptokinase IgG and subclass IgG1 in 95 subjects from the general population and in 160 patients presenting with acute myocardial infarction. Low titres of IgG1 were found in both the general population (median = 5; range: 0-490) and in the myocardial infarction group (median = 7; range: 0-2000). A minority of subjects in both groups had high titres. The findings suggest that low titres of antibody are widespread in the population. The minority of subjects in both groups who had high titres may explain the infrequent type III immune reactions encountered with streptokinase.

Overt and subclinical reactions to streptokinase in acute myocardial infarction.

The aims of this study were (1) to assess the possibility of predicting allergic reactions to streptokinase (SK) by measuring pretreatment antibody titers and by intradermal skin testing, and (2) to determine if SK is associated with subclinical changes in renal function. Specific anti-SK immunoglobulin G (IgG) and subclass IgG1 were assessed by enzyme-linked immunosorbent sorbent assays, and renal function was assessed by measurement of serum urea and creatinine in 204 patients with acute myocardial infarction. Twenty-six patients had 24-hour proteinuria loss and creatinine clearance assessed at presentation. Median IgG titer at presentation was 6 (range 0 to 10,000), and increased to 60 (range 0 to 18,000; p < 0.0001) on day 6. Fifteen of 180 patients (8.3%) had minor allergic reactions to SK; the median titer on admission for these patients was 5 (range 0 to 60), identical to those who tolerated SK uneventfully. No change was seen in serum urea or creatinine; for those treated with SK, the median value for proteinuria loss at day 0 was 0.45 g/liter (range 0.1 to 2), and decreased by day 5 to 0.1 g/liter (range 0.1 to 0.8; p = 0.0027). No significant proteinuria was seen in those who did not receive SK. The reactions to SK were minor, and could not be predicted on the basis of IgG titers at presentation. Significant proteinuria was found in the first 24 hours in SK-treated patients, but not in those who did not receive SK, and it resolved by day 5.

The significance of anti-streptokinase antibodies.

Antibodies to streptokinase (SK) are widespread in the population, but reports of their effect on the action of SK are conflicting. Specific anti-SK IgG was purified from the sera of 10 patients, five with low titres of anti-SK IgG and five with high titres. The effect of increasing specific anti-SK IgG antibodies on the action of SK was evaluated in vitro using a fluorimetric assay for plasmin and by a fibrin plate lysis assay. The inhibition of SK by whole plasma from a further group of patients was also assessed by the fibrin plate assay. There was a positive correlation between the serum antibody concentration and the quantity of specific anti-SK eluted (r = 0.797; P < 0.005). The addition of specific anti-SK IgG caused a dose-related decrease in SK activity (fluorimetric assay r = -0.93; P = 0.02; fibrin plate assay r = -0.98; P < 0.001). The addition of patient plasma to the fibrin plate assay also resulted in decreased lysis, which was dependent upon antibody titre (r = -0.95; P < 0.0001). Significant in vitro reduction of the activity of SK by specific antibody was demonstrated, and this was similar with plasma containing comparable amounts of antibody. The findings suggest that treatment with SK would be unlikely to induce an effective thrombolytic state when antibody titres are high (such as those seen within 2 years of an initial dose of SK).

Acute myocardial infarction in diabetic patients in the thrombolytic era.

To examine the benefits of thrombolytic therapy in diabetic patients with acute myocardial infarction a retrospective study of all diabetic and non-diabetic patients with acute myocardial infarction admitted to the coronary care unit of the General Hospital, Birmingham between January 1984 and December 1987 was made and findings compared to corresponding groups admitted between January 1990 and May 1992 when thrombolytic therapy was routine. In-hospital mortality and morbidity were assessed in 208 diabetic and 1029 non-diabetic patients with acute myocardial infarction admitted 1984 and 1987 and in 115 diabetic and 501 non-diabetic patients with myocardial infarction between January 1990 and May 1992. Following the introduction of thrombolytic therapy, there was a reduction in mortality among non-diabetic patients from 17% to 8.5%; p < 0.001 (observed reduction: 49%; 95% CI: 30-70%) and in the incidence of left ventricular failure (from 22% to 8%, p < 0.1 (observed reduction: 52%; 95% CI: 40-85.5%). Diabetic patients showed a reduction in mortality from 30% to 17%; p = 0.02 (observed reduction: 42%; 95% CI: 9.4-73.8%) and in the incidence of left ventricular failure from 39% to 21%; p < 0.01 (observed reduction: 45%; 95% CI: 20.3-72.5%). Thrombolytic therapy confers a major benefit on diabetic patients with acute myocardial infarction, although this group remains at a prognostic disadvantage compared to non-diabetic patients.

Why do patients develop reactions to streptokinase?

Minor reactions to streptokinase are not uncommon, although the etiology is unknown. It is widely presumed, however, that these, like the more serious immune reactions, are antibody-mediated. We measured specific anti-streptokinase IgG, subclasses IgG1, IgG2, IgG3, IgG4 and IgE by ELISAs, haemagglutination, indirect Coombs' test and immunoblotting in six patients who developed reactions to streptokinase. Evidence of complement activation by streptokinase was sought by a haemolytic complement assay and by measurement of C3, C4 and C3d. The patients who reacted to streptokinase presented with low titres of anti-streptokinase IgG (median = 5; range 0-32) and IgG1 (median = 3; range 0-14). No evidence of any other IgG subclass was found, nor of specific anti-streptokinase IgE. Anti-streptokinase IgG1 was found to fix complement; patients who reacted to streptokinase were found to have low levels of total complement 1 year post reaction. Probable aggregates and fragments of human albumin (added stabilizer) were found in the streptokinase preparation and proved to be antigenic in some patients, but were not found to be related to the development of reactions. The findings suggest that patients who develop reactions to streptokinase cannot be predicted on the basis of antibody titres at presentation. Minor reactions to streptokinase would not appear to be antibody-mediated, although complement activation may be involved.

Fatal myocardial infarction in hypertrophic cardiomyopathy associated with non-penetrating chest trauma.

Myocardial infarction as a result of injury to the coronary arteries is a rare complication of non-penetrating chest trauma. We report a case of fatal inferior wall myocardial infarction following traumatic injury to the right coronary artery, complicated by atrioventricular dissociation, in a patient with a combination of hypertrophic cardiomyopathy and non-occlusive coronary artery disease.

Immunoglobulin response to intravenous streptokinase in acute myocardial infarction.

OBJECTIVE: To devise assays to assess and follow the specific antibody response in patients treated with streptokinase for acute myocardial infarction. DESIGN: Venous blood samples were collected before treatment with streptokinase started and subsequently at regular intervals over one year. Specific IgG and subclass IgG1 were assessed by an enzyme linked immunosorbent assay. SETTING: Coronary care unit in a general hospital. PATIENTS: 48 patients with acute myocardial infarction: 22 patients had venous blood samples taken at presentation only; serial blood samples were taken from 20 patients who then received thrombolytic therapy with streptokinase and six patients who were unsuitable for thrombolytic therapy. RESULTS: Titres of antibodies to streptokinase were low at presentation in 36 (75%) of the 48 patients. Serial measurements made in 20 patients showed the virtual disappearance of antibody within the first 24 hours. This was followed by a steady increase in the specific IgG1 titre, which peaked at day 14 before gradually declining. Values at one year remained significantly higher than baseline values. There was no evidence of an IgM response in the patients studied. CONCLUSION: Low titres of antibodies to streptokinase were widespread in the population. Antibody was consumed after treatment and the subsequent immunoglobulin rise suggested a secondary immune responses; the recently described neutralising capacity to streptokinase is probably related to this antibody.

Influence of racial origin on admission rates of patients with suspected myocardial infarction in Birmingham.

All patients with suspected myocardial infarction admitted to hospital in four Birmingham health districts were studied to test the hypothesis that Asian patients would be overrepresented and Caribbean patients underrepresented compared with the indigenous population. One thousand four hundred and ninety six patients had a final diagnosis of myocardial infarction or severe angina pectoris. The relative risk of admission for Asian men compared with white men aged 45-64 years was 2.65 (95% confidence interval 2.20 to 3.19) and the risk for Asian men was high for both myocardial infarction and ischaemia when analysed separately. The relative risk of admission for Caribbean men compared with white men was 0.53 (95% CI 0.33 to 1.20). The relative risk for Asian women compared with white women in the same age group was 2.58 (95% CI 1.68 to 3.96), but this was due to an excess of admissions diagnosed as ischaemia rather than infarction in the Asian women. For Caribbean and white women the risk of admission was the same, although significantly fewer Caribbean women were admitted with myocardial infarction. The study was undertaken in 1986-87 and population data had to be derived from the 1981 census. The resident population changed in those five years and so the results were recalculated making allowances for these changes in the health districts involved. Based on these data the admission rate for Asian men with suspected myocardial infarction aged 45-64 was nearly twice that for white men (1.8): the relative risk of admission for Asian men compared with white men was 2.04 (95% CI 1.53 to 2.18). For Caribbean men the relative risk compared with white men was 0.45 (95% CI 0.29 to 0.71). For Asian women the relative risk of admission calculated from the adjusted census data resemble that in white women aged 45-64 years. The relative risk for admission with coronary heart disease in Asians is higher than expected work; one possible explanation for this is that the Asian population resident in the area under study was larger than estimated. The single major difference in risk factors was the high prevalence of diabetes mellitus in Asians (19.5% compared with 8.3% for white residents) but this did not wholly account for the excess of admissions from the Asian community.

Association of transient abnormal Q-waves during exercise testing with a stenosis of the main stem of the left coronary artery.

Transient electrocardiographic changes resembling acute myocardial infarction, with Q-waves and ST-segment elevation, have been reported in a variety of clinical situations in which evidence for acute myocardial necrosis was not apparent. Such electrocardiographic changes resolved to normal within minutes. We report a case in which exercise testing induced a painless reversible electrocardiographic abnormality identical to acute anterior myocardial infarction, and subsequent angiography revealed a severe stenosis in the proximal left coronary artery. We suggest that patients presenting with this type of electrocardiographic exercise response should proceed to urgent coronary angiography.

A controlled trial of GL enzyme in the treatment of acute myocardial infarction.

GL enzyme (hyaglosidase) is a highly purified component enzyme of hyaluronidase. A therapeutic trial was carried out in the treatment of suspected myocardial infarction among 1,488 patients presenting within 6 h of the onset of symptoms. No significant reduction in mortality at 6 months was observed in the GL group (15.7%) compared with the placebo group (16.4%). Mortality at 2 weeks was also unaffected by treatment (GL 10.3%; placebo 10.9%).

Myocardial infarct size and mortality in diabetic patients.

The mortality rate from myocardial infarction is disproportionately high in diabetic patients. One explanation for this may be that diabetic patients incur more extensive myocardial necrosis. This possibility was examined in a three part study. Firstly, peak serum aspartate aminotransferase concentrations of all diabetic and non-diabetic patients admitted with myocardial infarction over a 16 year period were compared retrospectively. Secondly, peak aspartate aminotransferase concentrations in a series of diabetic patients and controls matched by age and sex were examined retrospectively. Thirdly, creatine kinase MB release and electrocardiographic measures of infarct size were investigated prospectively in a case/control study. Although cardiac failure and death were more common in the diabetic groups, there were no significant differences in estimates of infarct size between diabetic and non-diabetic patients in any of the studies. Therefore, the high case fatality rate amongst diabetic patients is not caused by increased myocardial damage. Presumably survival is prejudiced by factors operating before the infarction.