EFFECT OF LIDOCAINE ON CONDUCTION IN CANINE PURKINJE FIBERS AND AT THE VENTRICULAR MUSCLE-PURKINJE FIBER JUNCTION

¹ Departments of Pharmacology and Medicine, College of Physicians and Surgeons, Columbia University, New York, New York

The purpose of this study was to determine in Purkinje fibers (PF) the effects of lidocaine on conduction and its determinants and to measure its effects on conduction and refractoriness at the ventricular muscle-Purkinje fiber junction (VM-PFJ). Preparations of papillary muscle and false tendon (Purkinje fibers) were obtained from dog hearts, placed in a bath perfused with Tyrode's solution, stimulated electrically and studied under control conditions and during perfusion with lidocaine. Transmembrane voltage (TMV) of ventricular muscle and of PF was recorded with microelectrodes. The effects of lidocaine on the characteristics of PF phase O depolarization, membrane responsiveness, conduction velocity and on conduction and refractoriness at the VM-PFJ were studied. A 1 x 10^-5 M lidocaine concentration produced effects thought to be equivalent to those seen after therapeutic doses in vivo. In PF, this concentration reduced automaticity and produced a maximal decrease in the duration of the action potential and effective refractory period without showing significant effects on maximal diastolic TMV or action potential amplitude and overshoot. This concentration of lidocaine had three effects on membrane responsiveness: 1) it shifted V_i (the least negative TMV at which the PF can be activated) to more negative values; 2) it steepened the slope of the relationship between phase 0 V_max and membrane activation voltage (MAV); and 3) it increased peak V_max. Conduction velocity in PF either increased or did not change after application of 1 x 10^-5 M lidocaine and conduction was markedly enhanced and refractoriness abbreviated at the VM-PFJ. High concentrations (1 x 10^-4 M) produced decreases in maximal diastolic TMV and in the amplitude, overshoot and V_max of phase 0 depolarization. These concentrations: 1) caused shifts in V_i to even more negative values of TMV; 2) shifted V_h (the TMV at which V_max is half the peak value) to more negative TMV; and 3) decreased peak V_max. At these concentrations, PF conduction velocity was significantly reduced and conduction and refractoriness at the VM-PFJ were prolonged over the values found at lower lidocaine concentrations.

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