The effect of local anaesthetics on strophanthidin toxicity in canine cardiac Purkinje fibres

Abstract

1. Canine Purkinje fibres were superfused in vitro and the electrical and mechanical effects of the local anaesthetics benzocaine and procaine were studied in the absence and in the presence of other agents.2. Both benzocaine (1 x 10(-4)-5 x 10(-4)m) and procaine (6 x 10(-5)-2.5 x 10(-4)m) decreased slightly the amplitude of the upstroke and markedly the duration of the action potential. The plateau was shifted to more negative values and the force of contraction was decreased. These effects were dose-dependent.3. The local anaesthetics abolished the spontaneous activity induced by strophanthidin (5 x 10(-7)m) by flattening the oscillatory potential in diastole and increased the force of contraction under these circumstances.4. The local anaesthetics significantly delayed the time of the onset of the spontaneous activity induced by strophanthidin (10(-6)m). Also, the intensity of the stimuli had to be increased and the rate of discharge of intoxicated fibres was slower in the presence of local anaesthetics. In contrast, the positive inotropic effect was little affected.5. The local anaesthetics reduced but did not block the inotropic action of norepinephrine and high Ca; and did not abolish (while Mn did) small action potential in 27 mm-K-depolarized fibres.6. In fibres treated with local anaesthetics, lowering [Ca](o) did not result in a force rebound and administration of caffeine or exposure to low Na resulted in a larger increase in force.7. In fibres loaded with Ca, local anaesthetics caused an increase in force.8. Local anaesthetics decreased the force more when the external Na concentration was lower.9. This work shows that the local anaesthetics alter the mechanical performance of Purkinje fibres and lead to a depression of the strophanthidin induced oscillatory potential. As for the mechanism for these changes, the present experiments support the hypothesis that local anaesthetic agents have an antiarrhythmic action by decreasing intracellular Na and therefore intracellular Ca as suggested by Perry, McKinney & DeWeer (1978) on the basis of experiments on nerve.