Contraction Dependency of the Positive Inotropic Action of Cardiac Glycosides

The concept that the positive inotropic effect of cardiac glycosides is dependent on the contractile state of the myocardium was tested. Isolated left atria of rabbits, when driven electrically at 15, 30, 60 and 120/min (at 30, 33, or 37°C), responded to ouabain (I µ/ml) in proportion to the number of contractions and not to the time of exposure or frequency of drive. Contraction-related effects were proportional to concentration of ouabain, acetylstrophanthidin, and digoxin. A contraction-related effect of ouabain was observed in anesthetized dogs with surgical A-V block, ventricular electrical drive and right ventricular contractile force recording. Quiescent rabbit atria exposed to ouabain for 30 min at 30°C and then washed in ouabain-free medium, showed minimal positive inotropic effect when stimulation was resumed. Toxic concentration of ouabain (5 µg/ml) in contact with quiescent atria for 30 min and then washed out, on resumption of stimulation had an immediate positive intropic (but no toxic) effect which diminished progressively, in contrast to the rapid development of toxic effects (ectopic contractions and contracture) in atria exposed to this dose of auabain during repetitive contractions. It is concluded that a major part of the positive intropic effect of cardiac glycosides is contraction dependent.