We evaluated a diagnostic strategy by studying 481 patients suspected of having had an acute myocardial infarction; the prevalence of infarction by independent criteria was 0.43. This strategy is based on the sequential application of: (a) clinical criteria; (b) total creatine kinase determinations in two serum samples drawn within 10 to 20 h of the onset of acute symptoms; and (c) creatine kinase B-subunit (S-CK B) determinations after immunoinhibition with antibodies to creatine kinase M-subunit in the reaction medium in all samples found to have increased total creatine kinase activity. Discrimination limits of 150 U/L total creatine kinase for women and 200 U/L for men gave a diagnostic sensitivity of 0.99. Activities less than these limits in samples identified 68% of the 274 non-infarct cases (posterior probability of a negative result of 0.99) within 20 h. Subsequent determination of S-CK B in 292 patients who were positive by the discrimination limits for total creatine kinase verified myocardial infarction in 99% of 207 cases for which S-CK B exceeded the discrimination limit of 12 U/L. The strategy excluded 98% of all non-infarct cases at a posterior probability of 0.99.
Tocainide is structurally related to lidocaine but may be used orally as well as intravenously. A therapeutic plasma concentration range of 25 to 45 mumole/l has been suggested. Tocainide kinetics were studied in 6 healthy subjects and 16 patients with acute myocardial infarction. There was good accordance in kinetics of healthy subjects and patients. After intravenous administration the mean t1/2 was about 14 hr, volume of distribution about 3.0 l/kg, and corrected renal clearance about 140 ml/min. An average of 35% of the dose was recovered unchanged in urine. After oral administration the absorption rate was rapid relative to the elimination rate, extent of bioavailability was complete, and the apparent volume of distribution was the same as that after intravenous injection. A dose regimen of 750 mg intravenously directly followed by 800 mg orally and subsequently 400 mg 3 times daily resulted in therapeutic plasma levels within 15 min. The plasma levels remained within the therapeutic range throughout a period of observation from 48 to 168 hr.
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