DISSOCIATION OF CARDIAC INOTROPIC AND TRANSMEMBRANE ACTION POTENTIAL EFFECTS OF OUABAIN

¹ National heart and Lung Institute, Bethesda, Maryland

The positive inotropic effect of ouabain may be due to a change in the distribution of ionized Ca⁺⁺ within the myocardial cell. The role of Ca⁺⁺ in the cardiac action of ouabain was explored in a preparation of intact ventricular myocardium allowing analysis of some cellular mechanisms as well as organ responses. The positive inotropic effects of ouabain and catecholamines were also compared to note possible differences in basic mechanisms. Tension development, dT/dt and transmembrane action potentials were recorded from right ventricular papillary muscles from normal and chronically denervated cat hearts. Ouabain. 4 x 10^-7 M. in Krebs' solutions with Ca⁺⁺ concentrations ranging from 0.15 to 2.5 mM was added to the muscle bath. In both normal and denervated papillary muscles outbain produced a negative inotropic effect of -14% at 0.15 mM Ca⁺⁺ and -11% at 0.30 Ca⁺⁺. Above 0.60 mM Ca⁺⁺. ouabain produced an increasing positive inotropic effect reaching a plateau at +28% at 2.5 mM. The effect on the transmembrane action potentials normally seen with ouabain (an acceleration of repolarization) was noted even in the face of a negative inotropic effect at low Ca⁺⁺ concentrations. In contrast to ouabain. both norepinephrine and isoproterenol produced positive inotropic effects at 0.15 mM Ca⁺⁺. These data demonstrate that in low Ca⁺⁺ it is possible to have a dissociation of the inotropic effect of ouabain and its cellular effect as manifested by a change in electrical parameters.