THE ACTION OF SODIUM PENTOBARBITAL ON THE S-A NODAL ACTIVITY OF THE MAMMALIAN HEART

¹ Department of Pharmacology, Harvard Medical School, Boston, Massachusetts

The effect of sodium pentobarbital on the S-A nodal activity of the HLP of the dog and of isolated spontaneously beating guinea-pig atria was investigated. The mean heart rate of 10 control HLP (initial heart rate: 137 ± 14 beats/min; blood volume: 1200 ml) was not changed by the administration of 40 to 160 mg of sodium pentobarbital. These doses decreased the competence of the heart as indicated by the rise in right atrial pressure and a decrease in systemic output. The dose of 165 ± 33 mg sodium pentobarbital reduced the systemic output to 60% of its initial value.

If the heart rate was increased in the HLP by an infusion of 3 µg/minute norepinephrine (mean rate increase in 9 experiments 55 ± 20 beats/min), sodium pentobarbital had a rate-decreasing activity. The dose of 199 ± 30 mg of sodium pentobarbital inhibited by 50% the rate increase caused by the norepinephrine infusion. During the norepinephrine infusion 402 ± 97 mg of sodium pentobarbital were needed to reduce the systemic output to 60% of initial. The ratedecreasing action of sodium pentobarbital could be seen as well, when the heart rate was increased by release of endogenous norepinephrine due to the administration of either 3 mg of reserpine or 10 mg of guanethidine to the HLP.

The maximal rate increase in the HLP caused by the administration of 2 to 3 mg of ephedrine was reduced from 101 ± 9 beats/minute (8 experiments) to 83 ± 9 beats/minute (5 experiments) in the presence of 105 mg of sodium pentobarbital (blood volume: 800 to 1000 ml).

In isolated guinea-pig atria (Krebs-Henseleit solution, 37°C) sodium pentobarbital had a negative chronotropic action in concentrations of 0.01 to 0.1 mg/ml. The force of contraction was also strongly impaired by 0.06 to 0.1 mg/ml.

Dose-response experiments with norepinephrine in isolated guinea-pig atria showed that the maximal rate increase caused by the administration of norepinephrine was reduced from 104 to 93% ( P .001) in presence of 0.06 mg/ml of sodium pentobarbital.

In the HLP accelerated by infusion of norepinephrine and in spontaneously beating pig atria, the rate decrease caused by a given concentration of sodium pentobarbital is dependent upon the rate before the administration of the drug, i.e., only if the pacemaker activity exceeds a certain level can sodium pentobarbital exert a negative chronotropic effect. The S-A nodal rate of the normal HLP is close to this critical level.