Electrophysiological effects of droperidol in different cardiac tissues

The effect of droperidol in concentrations between 0.05 and 5 mg/I was evaluated on different electrophysiological variables in auricular preparations of the guinea-pig, papillary muscles of dog and cat, Purkinje fibres of the dog, cow and sheep. At low concentration (0.25 to 0.5mg/I) droperidol decreased pacemaker activity and prolonged the effective refractroy period. The inhibition of pacemaker activity was not accompanied by a reduction in the rate of early diastolic depolarization, but was related to an inhibition of the depolarization process during late diastole. At high concentrations (5mg/I) resting potential, action potential amplitude, (dV/dt)max and conduction velocity were reduced. Reduction of dV/dt during the upstroke was more pronounced at lower membrane potentials, the inactivation curve was shifted to more negative membrane potentials. The action potential was lengthened or shortened, the effect being dependent on the frequency, dose, exposure time and animal species. Droperidol had no deleterious effect on Ca-mediated action potentials. The antiarrhythmic activity of droperidol in therapeutic concentrations (0.25 and 0.5mg/I) can be explained by the reduction of pacemaker activity and the lengthening of the effective refractory period. In terms of changes in ion conductance most effects can be explained by a reduction in Na conductance. No simple explanation can be offered for the complex changes in action potential duration.