The effects of diazepam on rat isolated heart muscle.

Abstract

SUMMARY1. The effects of diazepam on spontaneously beating right atrium, left atrium and papillary muscle isolated from a rat heart were compared to those of chlorpro‐mazine and phenytoin.2. Arrhythmic contractions induced by threshold electrical stimulation in the rhythmic spontaneous contractions of the right atrium were prevented by diazepam (10 μg/ml). These arrhythmic contractions were not prevented by chlorpromazine (0.01–10 μg/ml), or by phenytoin (0.1–10μg/ml).3. The refractory periods of the heart muscle, estimated by use of Govier's method, was increased by diazepam (10 μg/ml) by 90.5% in the left atrium and 54.4% in the papillary muscles. Chlorpromazine (1.0 μg/ml) and phenytoin (10 μg/ ml) increased the refractory period of papillary muscle by 42.8 and 54.1%, respectively, but had little effect on the refractory period of the left atrium.4. The maximum driving frequency of the left atrium was decreased by diazepam (10 μg/ml) by 25.1% and by chlorpromazine (1.0 μg/ml) by 33.3%, while that of papillary muscle was little influenced by the drugs at these concentrations. Phenytoin (0.1–10 μg/ml) had little effect on the maximum driving frequency of the left atrium or of papillary muscle.5. The rate and force of spontaneous contractions of the right atrium were decreased by phenytoin (10 μg/ml) by 36.7% and 97.0%, respectively. Diazepam (0.1–10 μg/ml) had little effect on rate and produced a concentration‐dependent increase in force up to 151.5%. Chlorpromazine (0.01–1.0 μg/ml) had little effect on either the rate or force of spontaneous contraction of the right atrium.6. The contractile force of the left atrium and of papillary muscle driven by electrical stimulation was depressed by diazepam (20 μg/ml), chlorpromazine (2.0 μg/ml) and phenytoin (20 μg/ml)‐ Diazepam (0.5–10 μg/ml) produced a concentration‐dependent increase in force of up to 204.7% in the left atrium and 163.1% in papillary muscle. Chlorpromazine (0.01–1.0 μ/ml) had little effect on the force of the driven left atrium, but produced a concentration‐dependent decrease in force of papillary muscle down to 40.1%. Phenytoin (10 μg/ml) reduced the force of contraction by 84.6 and 92.7%, respectively, in the left atrium and papillary muscle.