Effects of AY-22,241 (Actodigin) on electrical and mechanical activity of cardiac tissues

AY-22,241 (Actodigin) is a new rapid-acting semisynthetic cardiotonic steroid. In experiments on contractility of cat papillary muscle, Actodigin (2 times 10(-7) to 4 times 10(-6) M) produced a dose-dependent positive inotropic effect, a marked increase in the maximum rate of force development, and no change in resting tension. Electrophysiologic studies performed with microelectrode techniques on isolated Purkinje fibers superfused with Tyrode solution, revealed dose-dependent decreases in resting membrane potential, action potential amplitude and duration, and the maximum rate of rise of phase 0 (Vmax). Purkinje fibers superfused with extracorporeally circulated blood from a donor dog receiving 0.075 mg/kg/min Actodigin showed small decreases in resting membrane potential preceding the onset of donor premature ventricular contractions. Progressive decreases in resting membrane potential, action potential amplitude and duration, and Vmax accompanied donor ventricular tachycardia. All effects were rapidly reversible, and compared to ouabain, equi-inotropic concentrations of Actodigin caused significantly less electrophysiologic toxicity.