The influence of ischaemia on the electrophysiological properties of amiodarone in chronically treated rabbit hearts

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Abstract
The effects of 30 min zero-flow ischaemia and reperfusion on the electrophysiological properties of amiodarone were studied in 11 rabbits treated with oral amiodarone (mean 117 mg kg -1 day -1) for 2–3 months, and 11 controls. Experiments were performed in vitro in the isolated perfused interventricular septum, and preischaemic values were compared with those obtained in right ventricular papillary muscles from the same hearts. Prior to ischaemia, mean values of action potential duration (APD90 and effective refractory period (ERP) were prolonged by 13% in the amiodarone-treated septa. Action potential upstroke velocity (Vmax) was reduced by 14% in the septa, but by 42% in papillary muscles. Ischaemia resulted in shortening of APD90 in both control and amiodarone-treated septa, with a loss of the ability of amiodarone to prolong APD90. In contrast, ischaemia resulted in a greater fall in Vmax, gross lengthening in conduction time and increase in stimulation threshold in the amiodarone-treated septa compared with controls. Reperfusion resulted in a restoration of the action of amiodarone on repolarization, and resolution of the marked effects on excitability and conduction. The electrophysiological properties of amiodarone are considerably altered in ischaemic myocardium, with a reversible loss of its ability to prolong repolarization, but evidence suggestive of a marked enhancement of its effect on the inward sodium current.