Effect of quinidine on positive inotropic action of digoxin

To determine whether digoxin-quinidine interaction alters the inotropic effect of the glycoside, the response of peak isometric force and maximal rate of force development (dF/dt) in isolated feline right ventricular papillary muscles to digoxin and quinidine alone, and in various combinations, was examined. The administration of 1.3 or 2.6 x 10(-5) M of quinidine after 2 x 10(-7) M of digoxin resulted in an increase in contractile performance in each animal. Although 1.3 x 10(-5) M of quinidine alone produced a positive inotropic effect, 2.6 x 10(-5) M of quinidine produced no such effect. Because myocardial digoxin content has been reported to decline after administration of quinidine these results suggest that the increase in contractile performance when quinidine was administered after digoxin is due to displacement of digoxin from less to more active myocardial sites. The administration of 2 or 4 x 10(-7) M of digoxin after 2.6 x 10(-5) M of quinidine resulted in a minimal increase in force and rate of force development. A similar inhibition of the inotropic effect of digoxin was found in rabbit papillary muscles pretreated with quinidine. Inhibition was not limited to digoxin because pretreatment of muscles with quinidine also inhibited the inotropic effect of acetylstrophanthidin. Thus, quinidine has diametrically opposite effects on digitalis-induced inotropy dependent on the sequence with which the drugs are administered.