Influence of temperature and rate on the effectiveness of nifedipine in isolated rat heart preparations.

The negative inotropic effect of nifedipine (0.1-2.5 mg/l) was studied on isolated atria at different temperatures (36 degrees, 29 degrees, 22 degrees C) and frequencies of stimulation (20, 60, 180/min). The effect on peak force and dF/dt increased with dose, frequency and cooling from 36 degrees to 29 degrees. Rate of contraction was affected slightly more than rate of relaxation. The effect on time to peak was small, dose and frequency independent but potentiated by lowering the temperature. An analysis of mechanical transients showed that at 22 degrees C and 180/min stimulation the effect of nifedipine gradually diminished and only slowly reappeared upon transition to 20/min stimulation. In spontaneously beating perfused hearts the effects of nifedipine (0.5 mg/l) in general did not differ significantly at 36 degrees and 23 degrees C. The heart rate was reduced and atrioventricular conduction prolonged. At constant heart rate, nifedipine considerably depressed contractions, shortened the action potential duration and reduced the height of plateau. These effects of nifedipine are similar to those of verapamil in other animal species and the results support the idea that calcium antagonists might have secondary intracellular effects apart from direct consequences of slow current inhibition.