Different Chronotropic and Inotropic Effects of EMD 57033 and EMD 53998, Ca²⁺ Sensitizers, on Isolated, Blood-Perfused Dog Heart Preparations

Abstract

To investigate whether a Ca²⁺ sensitizer increases sinus rate, we studied the effects of racemic thiadiazinone, EMD 53998 (a Ca²⁺ sensitizer with phosphodiesterase inhibitory action) and its (+)-enantiomer EMD 57033 (a relatively pure Ca²⁺ sensitizer) on isolated, blood-perfused spontaneously beating right atria and paced left ventricles of the dogs. EMD 53998 increased sinus rate dose-dependently, but EMD 57033 did not. Both substances increased atrial and ventricular contractile force. Propranolol did not affect the responses to each substance. These results suggest that the Ca²⁺ sensitizing action induced by EMD 57033 does not affect pacemaker currents directly.