Experimental Evidence for the Antiarrhythmic Action of Indoramin

Abstract

The effects of indoramin on cardiac conduction and its antifibrillatory action were investigated and compared with those of mexiletine (class I antiarrhythmic agent), sotalol, and prazosin. In isolated guinea pig atria, indoramin 1 microgram/ml reduced spontaneous rate by 31 +/- 1.0% (mean +/- SE, n = 6) and maximal driving frequency by 25 +/- 1.2% (n = 4). Mexiletine 3 micrograms/ml reduced maximal driving frequency by 35 +/- 1.4% (n = 4) but reduced spontaneous rate by only 13 +/- 2.0% (n = 4). In isolated, perfused, electrically driven (2.5 Hz) guinea pig hearts, indoramin 1 microgram/ml increased the ST interval by 22 +/- 1.9% (n = 6) with no effect on the QRS interval. Higher concentrations (3 micrograms/ml) also increased the QRS interval by 21 +/- 4.0%. In anaesthetized cats, indoramin 6 mg/kg i.v. (infused over 30 min) reduced systolic blood pressure by 36 +/- 3.6% (n = 6) and heart rate by 35 +/- 2.2%, and increased the ST interval by 31 +/- 5.3% and the effective refractory period by 45 +/- 3.2% but had little or no effect on the QRS interval (12 +/- 2.9%) and diastolic electrical stimulation threshold (7 +/- 6.8%). Indoramin 10 mg/kg increased the QRS interval and diastolic electrical stimulation threshold by 20 +/- 2.8 and 23 +/- 2.5%, respectively. Analogous experiments with mexiletine 15 mg/kg showed little changes in cycle length (7 +/- 1.3%), effective refractory period (21 +/- 2.8%), and the ST interval (6 +/- 2.5%); however, there was a marked increase in diastolic threshold (91 +/- 8.9%). Sotalol 15 mg/kg had a cardiac profile similar to that of indoramin.(ABSTRACT TRUNCATED AT 250 WORDS)