An Electrophysiologic Study of the Digoxin—Quinidine Interaction

To study the electrophysiologic mechanisms responsible for the digitalis-quinidine interaction, 27 mongrel dogs were given either quinidine alone, digoxin alone, or digoxin followed by the digoxin-quinidine combination, via the oral route for sufficient time to permit accumulation of steady-state plasma levels. As anticipated, digoxin levels increased significantly in the presence of quinidine (P less than 0.05). Whereas digoxin alone had no significant effect on the ECG, quinidine alone prolonged the Q-T interval (P less than 0.05), and the combination prolonged both the QRS complex and the Q-T interval (P less than 0.05). Digoxin alone had no significant effect on the Purkinje fiber transmembrane potential, whereas quinidine reduced action potential (AP) amplitude and maximum upstroke velocity (Vmax) significantly. The combination significantly reduced AP amplitude Vmax, and maximum diastolic potential and prolonged AP reduced AP amplitude, Vmax, and maximum diastolic potential and prolonged AP duration. The changes induced by the drug combination appeared to be the sum of changes induced by each drug alone.