Influence of Ouabain on the Forcefrequency Relationship in Cardiac Muscle

The effects of different concentrations (10-8 to 10-5M) of ouabain on frequencydependent positive inotropy were studied in rabbit papillary muscles. In the absence of ouabain an increase in the frequency of stimulation (from 15/min 30, 60, 90, and 120/min) produced a frequencydependent increase in the contractility in papillary muscles. Ouabain (10-8M), which did not produce any change in the contractility, also did not produce any change in the frequencydependent increase in the contractility. However, in the presence of 10-1M of ouabain the frequencydependent increases in the contractility were greater than those in the absence of ouabain. At a concentration of 10-6M of ouabain the frequencydependent inotropic effect was positive only at low frequencies (30, 60/min) whereas at higher frequencies (90, 120/min) the positive effect was transient. In the presence of still higer concentrations (2, 5×10-6M and 10-5M) of ouabain the frequencydependent positive inotropy was changed to negative inotropy and this effect was dependent upon the concentrations of ouabain. This ouabaindependent change to negative inotropic effect of frequency increases was not due to the lack of oxygen or energy supply. Also the negative inotropy for the same concentration of ouabain was directly related to the frequency of stimulation. There results indicate that the frequencydependent increase in the cardiac contractility is mediated through an inhibition of the sarcolemmal Mg++-dependent, Na+-K+-ATPase. Preinhibition of this enzyme system abolishes the frequencydependent positive effect and the latter shows an inverse relationship with the degree of preinhibition.