Ventricular fibrillation in a conscious canine preparation of sudden coronary death--prevention by short- and long-term amiodarone administration.

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Abstract
The antifibrillatory properties of short-term i.v. (10 mg/kg per h) and long-term (10 mg/kg per day for 24 days) oral amiodarone administration were examined in a conscious canine preparation of sudden coronary death. Here, ventricular fibrillation was produced by electrically induced left circumflex intimal injury and thrombosis in the presence of previous anterior myocardial infarction. On day 4 after anterior myocardial infarction animals were assigned to receive short-term i.v. or long-term oral amiodarone treatment. Animals within each group were randomly assigned to control or drug treatment. Neither short-term i.v. or long-term oral amiodarone treatment prevented the development of ST segment changes or premature ventricular beats, but both short-term i.v. amiodarone and long-term oral amiodarone administration significantly reduced the incidence of ventricular fibrillation (short-term i.v. amiodarone (n = 10), incidence of 60% vs. control (n = 10) incidence of 100%; P < 0.05; long-term oral amiodarone (n = 10), incidence of 20% vs. control (n = 11) incidence of 91%, P < 0.002). Both short-term i.v. and long-term oral amiodarone administration produced increases in the PR and rate-corrected QT intervals. However, prolongation of the corrected QT interval in the group receiving long-term oral amiodarone (61 .+-. 18 ms) was greater than in the group receiving short-term i.v. drug (31 .+-. 11 ms, P < 0.05). This discrepancy between effects of long-term oral and short-term i.v. amiodarone could not be based on differences in plasma (1.9 .+-. 0.2 vs. 2.7 .+-. 0.5 .mu.g/ml, respectively) or right ventricular myocardial concentrations (13 .+-. 2 vs. 24 .+-. 4 .mu.g/g, respectively). Apparently, while both long-term oral amiodarone and short-term i.v. amiodarone prevent ventricular fibrillation in the conscious dogs subjected to acute myocardial ischemia in the presence of previous anterior myocardial infarction, long-term oral amiodarone may have an additional electrophysiologic action and therefore greater efficacy.