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1. The pharmacokinetics of streptokinase (SK) and anistreplase in conventional dosage regimens of 1.5 x 10(6) i.u. of SK infused over 60 min and 30 units of anistreplase over 5 min were studied in 24 consecutive patients presenting with acute myocardial infarction, using a functional bioassay to assess concentrations. 2. The two agents were found to have similar volumes of distribution (5.68 and 5.90 l), but SK was cleared significantly more rapidly than anistreplase, resulting in a shorter terminal phase half-life (0.61 vs 1.16 h) and a shorter mean residence time (0.76 vs 1.55 h). [ABSTRACT FROM AUTHOR]

Objective: To evaluate the influence of pretreatment streptokinase resistance titre and the concentration of IgG antibodies to streptokinase on the efficacy of thrombolytic drugs containing streptokinase in restoring coronary patency in acute myocardial infarction., Design: Comparative observational study., Setting: City general hospital., Patients: One hundred and twenty four previously unexposed patients presenting within six hours of onset of acute myocardial infarction., Interventions: Streptokinase, 1.5 MIU as intravenous infusion over 60 minutes (60 patients), or anistreplase, 30 units as intravenous injection over five minutes (64 patients)., Main Outcome Measures: Pretreatment streptokinase resistance titre and concentration of IgG antibodies to streptokinase were measured in 96 and 124 patients respectively and coronary patency assessed angiographically at 90 minutes and 24 hours., Results: Pretreatment streptokinase resistance titre and concentrations of IgG antibodies to streptokinase were low and skewed towards higher values. Those patients with coronary occlusion at 24 hours had a significantly higher median streptokinase resistance titre (100 v 50 streptokinase IU ml-1, P = 0.02). There were trends towards a higher streptokinase resistance titre in those patients with coronary occlusion at 90 minutes (50 v 20 streptokinase IU ml-1, P = 0.06) and higher concentrations of IgG antibodies to streptokinase in those with coronary occlusion at both 90 minutes and 24 hours (1.53 v 0.925, P = 0.03; 1.65 v 1.04 micrograms streptokinase binding ml-1, P = 0.06). Coronary patency rates were similar in the two treatment groups., Conclusions: In the range measured in previously unexposed patients the streptokinase resistance titre has a small, but significant, negative influence on the efficacy of streptokinase and anistreplase. This effect should be considered if retreatment with streptokinase or anistreplase is proposed.

Objective: To assess the clinical ability of general practitioners to decide to give thrombolytic therapy to patients with suspected myocardial infarction and to assess the contribution of the electrocardiograph (ECG) to this decision-making process., Setting: 7 practices on the North side of Glasgow and the coronary care unit of Stobhill General Hospital., Subjects: 137 patients presenting with chest pain who required direct admission to the coronary care unit., Main Outcome Measures: Agreement between the general practitioner's clinical decision to give thrombolytic therapy with or without reference to the ECG and the prescription of thrombolytic therapy in the coronary care unit., Results: The predictive accuracy of the general practitioner's assessment of the necessity for thrombolytic therapy was 71.5%. The ECG had no impact on the accuracy of this decision and there were problems with the recording and interpretation of the ECG. Clinical decision making was altered in six cases by the ECG: wrongly in four., Conclusion: The diagnostic accuracy among general practitioners would result in some patients who did not have acute myocardial infarction being given thrombolytic therapy. In this study the ECG did not contribute towards diagnostic accuracy. Substantial improvement in both the recording and interpretation of ECGs is needed before thrombolytic agents can be routinely prescribed at home.

Eighty patients (43 M, 37 F), aged 23-89 years who were referred for emergency echocardiography over a 12-month period were prospectively studied in order to determine the reasons for emergency echocardiography and the influence of its results on patient management. The most frequent emergency request was to clarify whether the basis for cardiomegaly in a haemodynamically unstable patient was pericardial effusion or left ventricular dilatation. Other reasons for requests were for assessment for source of systemic emboli, acute complications of myocardial infarction, endocarditis, valve dysfunction and cardiac trauma. As a consequence of the emergency echocardiography, management was immediately influenced in 19 patients. This study has provided information on the specific settings in which emergency echocardiography can be justified.

The incidence, amplitude, mechanism and relationship to prior exposure to streptococcal antigen of blood pressure changes to streptokinase-containing thrombolytic agents were investigated in 125 patients treated with either 1.5 x 10(6) IU streptokinase over 60 min or 30 U anistreplase over 5 min, within 6 h of onset of acute myocardial infarction. Twenty-one of 52 patients with anterior and 34 of 73 with inferior myocardial infarction had a hypotensive response. There were no significant differences in the incidence, duration or amplitude of hypotension between the two treatment groups. The maximum mean fall in systolic blood pressure was 16.9 mmHg (95% confidence limits, CL 12.2 to 24.5 mmHg), and the maximum mean fall in diastolic blood pressure was 13.7 mmHg (CL 10.3 to 17.1 mmHg), starting 4 min after start of therapy and resolving within 34 min. Blood pressure changes were well tolerated. Hypotension was not related to pretreatment streptokinase resistance titre, or anti-SK IgG concentration, to changes in plasma fibrinogen, B-beta 15-42 peptide, D-dimer--as indices of thrombin activation and fibrin (-ogen) breakdown--to plasma viscosity. The blood pressure changes following treatment with streptokinase-containing thrombolytic agents in acute myocardial infarction are frequent but well tolerated. The mechanism of hypotension remains unclear, but is not related to prior exposure to streptococcal antigen.

Background: Sumatriptan (GR43175) is a selective 5-hydroxytryptamine (5HT1) receptor agonist effective in the acute treatment of migraine. Recent in vitro experiments suggest that it has vasoactive properties in vascular beds distinct from the cerebral circulation. The object of this study was to assess the vasoactive effects of the standard 6-mg subcutaneous dose of sumatriptan used in migraine on the systemic and pulmonary circulations and the coronary artery vasculature., Methods and Results: Ten patients undergoing diagnostic coronary arteriography were studied with digital subtraction angiography and invasive hemodynamic monitoring. After subcutaneous injection of sumatriptan, there was no significant change in heart rate or ECG morphology. There was a significant rise in the systemic (20%, p < 0.05 by ANOVA) and pulmonary artery (40%, p < 0.05 by ANOVA) pressures. There was no change in cardiac output, but there was a significant increase in total systemic (27%, p < 0.05) and total pulmonary vascular resistance (40%, p < 0.05). Sumatriptan caused a significant reduction (p < 0.001 by ANOVA) in mean absolute coronary artery diameter, from 4.36 +/- 1.60 mm at baseline to 3.67 +/- 1.49 mm (16%) at 10 minutes and to 3.63 +/- 1.49 mm (17%) at 30 minutes after injection. There were no clinical sequelae., Conclusions: Sumatriptan, a 5HT1 receptor agonist administered by the subcutaneous route, causes a vasopressor response in the systemic and pulmonary arterial circulations and coronary artery vasoconstriction.

1. Sumatriptan (GR43175) is a selective 5-HT1-receptor agonist effective in the acute treatment of migraine. Vasoactive properties in other vascular beds have been suggested by recent in vitro studies. 2. Its effects on coronary artery dimensions and central haemodynamics were assessed in 10 patients undergoing diagnostic coronary arteriography using digital subtraction angiography and invasive haemodynamic monitoring. 3. Following a 10 min i.v. infusion of sumatriptan to a total dose of 48 micrograms kg-1 there was a significant increase (P < 0.05) in systemic and pulmonary arterial pressures. There was a significant reduction in coronary artery diameter from 4.3 +/- 1.6 mm to 3.6 +/- 1.6 mm 12.9 +/- 6.9% (P < 0.001). There was no significant change in heart rate or ECG morphology. 4. Sumatriptan, a 5-HT1-receptor agonist, causes a vasopressor response in the systemic and pulmonary arterial circulations and coronary artery vasoconstriction; in this study there were no clinical sequelae.

Objective: To examine the induction of antistreptokinase antibodies after giving streptokinase or anistreplase to patients with acute myocardial infarction., Design: Patients were randomly allocated to receive either 1.5 x 10(6) IU, streptokinase or 30U anistreplase in a double blind study. Blood samples were collected immediately before treatment and subsequently at intervals up to 30 months; plasma samples were assayed for streptokinase resistance titre (functional assay) and streptokinase binding by IgG (microradioimmunoassay)., Setting: Cardiology department in a general hospital., Patients: 128 consecutive eligible patients. Samples were collected for up to one year according to a prospective design: a subsection of 47 patients was selected for intensive study over the first 14 days. After one year, all available patients (67) were sampled on one further occasion., Results: Antibody responses to streptokinase and anistreplase were similar. Streptokinase resistance titres exceeded pretreatment concentrations five days after dosing, and values peaked at 14 days. By 12 months after dosing, 92% of resistance titres (n = 84) had returned to within the pretreatment range. Antistreptokinase IgG concentrations also exceeded baseline concentrations within five days and peaked at 14 days. Half of the individual values had returned to within the pretreatment range by 12 months (n = 84) and 89% by 30 months (n = 18)., Conclusion: Although we cannot be sure of the clinical significance, because of the increased likelihood of resistance due to antistreptokinase antibody, streptokinase and anistreplase may not be effective if administered more than five days after an earlier dose of streptokinase or anistreplase, particularly between five days and 12 months, and increased antistreptokinase antibody may increase the risk of allergic-type reactions.

Objective: To examine the efficacy, safety, and the pharmacokinetic profile of a bolus dose administration regimen of alteplase in the treatment of acute myocardial infarction., Design: An open pilot study., Setting: District general hospital., Patients: 33 suitable consecutive patients presenting within six hours of the onset of symptoms who satisfied the electrocardiographic criteria for acute myocardial infarction., Interventions: Two intravenous boluses of 35 mg alteplase, 30 minutes apart., Main Outcome Measures: Angiographic coronary patency at 90 minutes and 24 hours. Plasma alteplase concentration-time profile and pharmacokinetic analysis., Results: Coronary patency at 90 minutes: 26 of 30 arteries (87%, 95% confidence interval (CI) 74-99%). Coronary patency at 24 hours: 24 of 29 arteries (83%, CI 69-97%). Mean (SD) plasma tissue plasminogen activator (t-PA) concentration reached 4434.8 (2117.8) and 4233.3 (2217.5) ng/ml within 10 minutes of each bolus and fell to 425.8 (288.3) ng/ml between boluses. The estimated peak concentrations at two minutes after boluses were 12,389 (8580) ng/ml and 10,811 (6802) ng/ml. The derived pharmacokinetic variables were volume of distribution 3.11 (1.89) 1, clearance 21.3 (9.3) 1/h, half life 5.9 (1.7) minutes., Conclusions: This simple administration regimen achieved brief, high concentrations of plasma t-PA that were well tolerated. The regimen was associated with a high coronary patency rate at 90 minutes that was well maintained at 24 hours.

128 patients with acute myocardial infarction of duration 6 h or less were randomised in double-blind fashion to receive 30 U anistreplase over 5 min or 1.5 MU streptokinase over 1 h, both intravenously. Angiographic patency was assessed 90 min and 24 h from the start of therapy. 55% of patients who received anistreplase and 53% of patients who received streptokinase had patent infarct-related arteries (TIMI grade 2-3) at 90 min (95% CI 42-68% and 40-66%, respectively). At 24 h 81% and 87.5% of arteries were patent respectively (95% CI, 71-91% and 83.5-91.5%). Time to therapy had no significant effect on patency rates. There was one early reocclusion within 24 h in each treatment group and clinical evidence of reocclusion was recorded between 24 h and hospital discharge in a further 5 patients (streptokinase 3, anistreplase 2). With these regimens, therefore, anistreplase and streptokinase gave the same patency rates.

The effects of intravenous edrophonium on plasma noradrenaline were studied in 12 subjects with primary autonomic failure. 5 had clinical features of central autonomic damage, 4 with parkinsonism (PD) and 1 with multiple system atrophy (MSA); the other 7 had clinical features of progressive autonomic failure without detectable central neurological damage (PAF). After edrophonium all but 1 subject showed falls in heart rate of about 6 beats/min; there were no consistent blood pressure changes. The 5 PD/MSA patients all had normal plasma noradrenaline responses to edrophonium, with rises of 35-66% within 2-8 min of injection. 6 of the 7 PAF patients had no response or very small responses (-6 to +11%), while the other subject had a normal response (70% rise). The noradrenaline response to edrophonium may provide a simple way to differentiate between central and peripheral autonomic damage.