Ouabain-induced negative frequency-force relationship in the isolated, blood-perfused dog atrium

Effects of ouabain, CaCl2 and verapamil on the frequency-force relationship (FFR) were investigated in the isolated, blood-perfused dog atrial muscle preparation. When ouabain (3 and 10 micrograms) or CaCl2 (0.5, 1 and 2 mg/min) was given into the sinus node artery, the contractile force of the atrial muscle, driven at a constant pacing rate of 2 Hz, increased dose-dependently. Verapamil (1 and 3 micrograms) decreased the atrial contractile force dose-dependently. When the pacing rate was changed from 2 to 3.5 Hz, the atrial contractile force increased in parallel with the pacing rate (positive FFR). After treatment with ouabain and verapamil, the contractile force declined at higher frequencies (negative FFR). The verapamil-induced negative FFR was much steeper than the ouabain-induced relationship. An infusion of CaCl2 modified the FFR such that higher doses of CaCl2 elicited a negative FFR only at higher pacing rates. However, the CaCl2-induced FFR did not differ from the negative FFR induced by verapamil or ouabain. It was demonstrated that the cardiotonic agents ouabain and CaCl2, as well as verapamil induced negative FFR in the isolated dog heart.