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

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Abstract
Canine Purkinje fibers were superfused in vitro and the electrical and mechanical effects of the local anesthetics benzocaine and procaine were studied in the absence and presence of other agents. Both benzocaine (1 .times. 10-4 to 5 .times. 10-4 M) and procaine (6 .times. 10-5 to 2.5 .times. 10-4 M) slightly decreased the amplitude of the upstroke and markedly decreased 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. The local anesthetics abolished the spontaneous activity induced by strophanthidin (5 .times. 10-7 M) by flattening the oscillatory potential in diastole and increased the force of contraction under these circumstances. The local anesthetics significantly delayed the time of the onset of the spontaneous activity induced by strophanthidin (10-6 M). The intensity of the stimuli had to be increased and the rate of discharge of intoxicated fibers was slower in the presence of local anesthetics. The positive inotropic effect was little affected. The local anesthetics 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 fibers. In fibers treated with local anesthetics, lowering [Ca]0 did not result in a force rebound and administration of caffeine or exposure to low Na resulted in a larger increase in force. In fibers loaded with Ca, local anesthetics caused an increase in force. Local anesthetics decreased the force more when the external Na concentration was lower. The local anesthetics alter the mechanical performance of Purkinje fibers and lead to a depression of the strophanthidin-induced oscillatory potential. The hypothesis that local anesthetic agents have an antiarrhythmic action by decreasing intracellular Na and therefore intracellular Ca is supported.