Effects of verapamil on canine Purkinje fibres and ventricular muscle fibres with particular reference to the alternation of action potential duration after a sudden increase in driving rate

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Abstract
Effects of verapamil on the action potential configuration of canine Purkinje fibres and ventricular muscle fibres were determined using microelectrode methods. Verapamil, in a concentration of 0.5 mg·litre−1 (about 1 x 10−6 mol·litre−1), shifted the action potential phase 2 to less positive potential levels in Purkinje fibres and caused the slope of phase 2 to increase. Verapamil, 2 mg·litre−1and 4.5 mg·litre−1, induced more marked changes in the action potential phase 2, remarkable slowing of repolarisation during phase 3 and the decreases in the maximum rate of depolarisation, action potential amplitude and the maximum diastolic potential of the Purkinje fibres. Verapamil showed similar effects on ventricular muscle fibres. But the ventricular muscle fibres seemed to be less sensitive to the drug than the Purkinje fibres, and the slowing of phase 3 by verapamil was unremarkable in the ventricular muscle fibres. When the driving rate was suddenly increased, successive action potentials showed an alternation of APD_60 mV (the time required for repolarisation to -60 mV from the rise of phase 0). It was found that this alternation had two types: the first was characterised by longer APD_60 mV of odd beats after a sudden increase in driving rate and the second was characterised by longer APD_60 mV of even beats. The former type occurred more prominently in ventircular muscle fibres than in Purkinje fibres and lasted longer than the latter type. Under certain conditions the types of the alternation in Purkinje fibres and of the alternation in ventricular muscle fibres were different from each other. It is quite possible that these phenomena aggravate arrhythmias. Verapamil, 0.5 mg·litre 1, had a marked inhibitory effect on the alternation characterised by longer APD_60 mV of odd beats. This effect may be one of the factors behind its preventive action on ventricular fibrillation.