Effects of Lidocaine, Propranolol, and Sotalol on Ouabain-lnduced Changes in Transmembrane Potential of Canine Purkinje Fibers

Abstract

Isolated canine papillary muscle-false tendon preparations stimulated at 95/min were perfused with Tyrode's solution containing ouabain, 2.1 x 10 -7 M. Action potentials of Purkinje fibers were recorded. Initially ouabain increased the slope of phase-4 depolarization. Subsequently it decreased the maximum diastolic potential and the rising velocity of phase 0, the amplitude, and the duration of the action potential. The slope of phase-4 depolarization increased progressively, and eventually the configuration of the action potential changed to resemble that of sinoatrial node fibers. Onset of enhanced phase-4 depolarization was delayed significantly by treatment before exposure to ouabain with lidocaine, 3.7 x 10 -5 M, or propranolol, 2.1 x 10 -5 M, but not with sotalol, 3.2 x 10 -4 M. Enhanced phase-4 depolarization produced by exposure to ouabain was reduced in slope by subsequent treatment with lidocaine or propranolol but not sotalol. Application of lidocaine or propranolol to fibers with action potentials in the configuration characteristic of sinoatrial node fibers returned the contour of the action potentials toward normal; sotalol was not effective in this regard. These results, coupled with the relative effectiveness of these drugs in intact animals with digitalis arrhythmias, support the hypothesis that enhanced phase-4 depolarization of Purkinje fibers is a factor in the production of digitalis-induced ventricular arrhythmias.