ACUTE AMIODARONE TERMINATES VENTRICULAR-FIBRILLATION BY MODIFYING CELLULAR CA-PERFUSED RAT HEARTS(+ HOMEOSTASIS IN ISOLATED)

Intravenous amiodarone has an acute antiarrhythmic action, which may b e mediated by effects on intracellular calcium concentration [Ca++]i. We evaluated termination of pacing-induced Ventricular fibrillation (V F) and associated changes in [Ca++]i by acute amiodarone in isolated p erfused rat hearts loaded with the [Ca++]i indicator amino-5-methylphe noxy)ethane-N,N,N',N'-tetraacetic acid pentaacetoxymethyl ester. [Ca+]i was evaluated with surface fluorometry through fiberoptics placed o n the interventricular septum. Two minutes after VF induction, hearts were perfused with amiodarone (n = 12, 10 mu g/ml for 5 min followed b y 1 mu g/mg, low extracellular calcium concentration [Ca++]o (n = 12, 0.2 mM) or a control perfusate (n = 12, no treatment). VF termination during a 30-min observation period was significantly more frequent wit h amiodarone (92%) and with low [Ca++](o) (75%) compared with no treat ment (17%, P < .05). In nontreated hearts without recovery, [Ca++]i ex pressed as a percentage of the base-line amplitude, increased continuo usly from 206% +/- 44% to 529% +/- 138% during 30-min VF (P < .05). In hearts that recovered with amiodarone and low [Ca++]o, [Ca++]i decrea sed significantly from 273% +/- 55% and 273% +/- 99% before treatment to 122% +/- 95% and 50% +/- 80% before defibrillation, respectively (P < .05). VF frequency was also significantly decreased with amiodarone . The nature of [Ca++]i transients in VF has not been fully known. Pow er spectrum analysis disclosed that [Ca++]i transients responded to ev ery one or two electrocardiographic signals in VF with the highest fre quency of 22 Hz. Rapid [Ca++]i transients may be responsible for [Ca+]i overload in VF. However, amiodarone did not clearly change this sty le of response. We conclude that amiodarone and low [Ca++]o successful ly terminated VF and that this effect was preceded by a significant de crease in [Ca++]i. This suggests that reduced [Ca++]i was an antifibri llatory mechanism of amiodarone.