Acute and chronic effects of amiodarone on delayed afterdepolarization and triggered automaticity in rabbit...

The effects of amiodarone on delayed afterdepolarization (DAD) and triggered automaticity induced by low potassium (0.5 mEq/L) were evaluated on isolated rabbit right ventricular muscles, by means of standard microelectrode techniques. Triggered automaticity was induced in 6 of 10 muscles in the control group, in four of eight in the amiodarone-superfused group, and in three of four in the Tween 80-pretreated group. In contrast, triggered automaticity could be induced in only 2 of 10 of amiodarone-pretreated muscles (n = 10) (20 mg/kg intraperitoneally, daily for 4 weeks; p less than 0.05 compared to control and amiodarone-superfused groups). The amplitude of DAD was significantly lower in muscles isolated from rabbits pretreated with amiodarone compared to those from nontreated control rabbits (n = 17). The degree of reduction was significant during all three cycle lengths of stimulation tested (800, 600, and 400 msec), that is, 2.5 +/- 1.8 vs 5.1 +/- 1.8, 2.4 +/- 2.1 vs 5.5 +/- 2.3, and 3.3 +/- 3.4 vs 9.3 +/- 4.3, respectively (values are in millivolts of mean +/- SD). Superfusion with amiodarone (3 micrograms/ml; n = 8) significantly (p less than 0.05) reduced the amplitude of DAD at 800 msec cycle length, but had no significant effect at cycle lengths of 600 and 400 msec. Tissue concentrations of amiodarone in the pretreated group were significantly (p less than 0.05) lower than those in the superfused group (10 +/- 6.8 vs 21 +/- 3.1 micrograms/gm).(ABSTRACT TRUNCATED AT 250 WORDS)