Relationship between myocardial amiodarone concentration and antiarrhythmic effect in dogs with myocardial infarction and electrically induced ventricular arrhythmias

The relationship between the antiarrhythmic effect of amiodarone and its myocardial concentration was studied in dogs with 1-week-old myocardial infarction and reproducibly inducible sustained ventricular tachycardia or ventricular fibrillation. Three groups of animals (n = 10/group) received amiodarone, 40 mg∙kg−1∙day−1 (low-dose amiodarone), amiodarone 60 mg∙kg−1∙day−1 (high-dose amiodarone), or no amiodarone (control group). After 1 week of treatment, programmed electrical stimulation was repeated, and plasma and myocardial amiodarone and desethylamiodarone concentrations were measured. In the control group, sustained ventricular tachycardia or ventricular fibrillation was induced in six dogs (p = NS) when compared with baseline data. In the low-dose amiodarone group, sustained ventricular tachycardia or ventricular fibrillation was induced only in two dogs after 1 week of treatment (p < 0.01 vs. baseline data). Sustained ventricular tachycardia or ventricular fibrillation was induced in seven dogs after treatment with high-dose amiodarone (p = NS vs. baseline data). Plasma amiodarone concentration in the low-dose amiodarone group (2.54 ± 1.9 μg/mL) was significantly less (p < 0.01) than that in the high-dose amiodarone group (4.64 ± 1.66 μg/mL). Similarly, the plasma desethylamiodarone in the low-dose amiodarone group (0.32 ± 0.16 μg/mL) was significantly less (p < 0.001) than that in the high-amiodarone dose group (0.56 ± 0.23 μg/mL). The myocardial amiodarone concentration in the low-dose amiodarone group (49.7 ± 23.1 μg/g) was significantly lower (p < 0.001) than that in the high-dose group (98.4 ± 32.1 μg/g). There was no significant difference in the myocardial desethylamiodarone concentrations between the two treatment groups (25.1 ± 12.2 μg/g in the low-dose amiodarione group vs. 37.4 ± 16.4 μg/g in the high-dose amiodarone group). These data show that the high-dose amiodarone regimen, which produced high myocardial amiodarone concentration, didn't suppress sustained ventricular arrhythmias.Key words: amiodarone, ventricular arrhythmias, plasma and myocardial drug concentrations.