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

The effects of 30 min zero-flow ischaemia and reperfusion onthe electrophysiological properties of amiodarone were studiedin 11 rabbits treated with oral amiodarone (mean 117 mg kg ^-1day ^-1) for 2–3 months, and 11 controls. Experiments wereperformed in vitro in the isolated perfused interventricularseptum, and preischaemic values were compared with those obtainedin right ventricular papillary muscles from the same hearts.Prior to ischaemia, mean values of action potential duration(APD₉₀ and effective refractory period (ERP) were prolongedby 13% in the amiodarone-treated septa. Action potential upstrokevelocity (V_max) was reduced by 14% in the septa, but by 42%in papillary muscles. Ischaemia resulted in shortening of APD₉₀in both control and amiodarone-treated septa, with a loss ofthe ability of amiodarone to prolong APD₉₀. In contrast, ischaemiaresulted in a greater fall in V_max, gross lengthening in conductiontime and increase in stimulation threshold in the amiodarone-treatedsepta compared with controls. Reperfusion resulted in a restorationof the action of amiodarone on repolarization, and resolutionof the marked effects on excitability and conduction. The electrophysiological properties of amiodarone are considerablyaltered in ischaemic myocardium, with a reversible loss of itsability to prolong repolarization, but evidence suggestive ofa marked enhancement of its effect on the inward sodium current.     

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

The effects of 30 min zero-flow ischaemia and reperfusion onthe electrophysiological properties of amiodarone were studiedin 11 rabbits treated with oral amiodarone (mean 117 mg kg ^-1day ^-1) for 2–3 months, and 11 controls. Experiments wereperformed in vitro in the isolated perfused interventricularseptum, and preischaemic values were compared with those obtainedin right ventricular papillary muscles from the same hearts.Prior to ischaemia, mean values of action potential duration(APD₉₀ and effective refractory period (ERP) were prolongedby 13% in the amiodarone-treated septa. Action potential upstrokevelocity (V_max) was reduced by 14% in the septa, but by 42%in papillary muscles. Ischaemia resulted in shortening of APD₉₀in both control and amiodarone-treated septa, with a loss ofthe ability of amiodarone to prolong APD₉₀. In contrast, ischaemiaresulted in a greater fall in V_max, gross lengthening in conductiontime and increase in stimulation threshold in the amiodarone-treatedsepta compared with controls. Reperfusion resulted in a restorationof the action of amiodarone on repolarization, and resolutionof the marked effects on excitability and conduction. The electrophysiological properties of amiodarone are considerablyaltered in ischaemic myocardium, with a reversible loss of itsability to prolong repolarization, but evidence suggestive ofa marked enhancement of its effect on the inward sodium current.