Influence of verapamil on the digoxin-induced inotropic effect in guinea-pig isolated atria

The nature of the digoxin-verapamil interaction was explored "in vitro" by determining the effect of verapamil on digoxin-induced inotropism in isolated guinea-pig atria. Verapamil, at concentrations (2.10(-8)-3.10(-8)M) too low to have any significant effect on the amplitude or frequency of the basal contractile activity, reduced the inotropic action of digoxin in all experimental circumstances, i.e. in spontaneously beating atria from reserpine-treated or untreated animals, in electrically driven (at 1 Hz frequency stimulation) left atria. The results obtained suggest that a competitive antagonism exists between verapamil and digoxin. In spontaneously beating atria an apparently competitive antagonism was also observed between verapamil and ouabain. The interaction observed between cardiac glycosides and the Ca++ channel blocker suggests that Ca++ movements across the sarcolemma may influence the inotropic effect of digitalis or its toxicity.