Changes of the inotropic effect of digoxin induced by drugs and cations in isolated rabbit heart preparation

Abstract

We have investigated the inotropic effect of digoxin on isolated rabbit heart and changes caused by various drugs, Ca2+ and Mg2+. The isovolumetric left ventricular pressure was measured using a balloon in a modified Langendorff perfusion apparatus. Digoxin at 2.5 x 10-7 - 0.5 x 10-6 mM produced positive inotropic effect, whereas at 2 and 2.5 x 10-6 mM there was a positive lusitropic action before the positive inotropic effect. Changes in the level of Ca2+ and Mg2+ significantly altered digoxin inotropicity. 5.04 mM of Ca2+ increased the positive inotropic effect of digoxin. Lowering the Ca2+ level to 1.26 mM or adding Mg2+ at 2.5 mM in the perfusion solution inhibited the inotropic effect. Atropine at 0.5 - 3 x 10-5 M produced a weak positive inotropic effect. Verapamil (1 x 10-6 -3 x 10-5 M), lidocaine (5 x 10-6 - 3 x 10-4 M) and propranolol (5 x 10-6 - 3 x 10-4 M) produced a negative inotropic effect. Diazepam at 5 x 10-6 - 3 x 10-4 M had a positive inotropic effect preceded by a brief negative inotropic effect. In the interaction studies, atropine non-significantly decreased the positive lusitropic effect of digoxin, but did not exert any significant action on the positive inotropic effect of digoxin. Verapamil, lidocaine and propranolol increased the positive lusitropic effect and antagonized the positive inotropic action of digoxin. Diazepam non-significantly modified the activity of digoxin. These results show the dose-dependent inotropic effect of digoxin, which was increased by Ca2+ and inhibited by Mg2+, verapamil, lidocaine and propranolol. The clinical significance of such interactions (decreased therapeutic and increased toxic effects) should be considered.