INFLUENCE OF MYOCARDIAL ACTIVITY ON THE RATE OF ONSET OF OUABAIN ACTION

¹ Pharmakologisches Institut der Universität Bern, Bern, Switzerland

The relationship between beat interval and the rate of onset of the positive inotropic effect of ouabain was examined in guinea-pig left atria maintained in Tyrode's solution at 35°C. Atria were driven at one of seven beat intervals ranging from 0.3 to 300 sec in the presence of ouabain (2 x 10µ-7 g/ml) and the time course of the action was followed. The rate of onset of ouabain action was not dependent on the beat interval at beat intervals greater than 3.0 sec. On the other hand, the rate of onset of ouabain action was accelerated at beat intervals of less than 3.0 sec. Experiments were also performed with guinea-pig and rabbit atria exposed to ouabain during a 50-min rest period. Subsequent stimulation showed that ouabain produced a positive inotropic effect on the resting atria. The results suggest that ouabain exerts a basal, time-dependent, positive inotropic effect on cardiac muscle at rest or near-rest and that the rate of onset of ouabain action is measurably increased above this basal value only when the muscle contracts at a greater than critical frequency.