[Cardiac disorders induced by mianserin in guinea pigs. Comparison with imipramine]

Infusion of mianserin to anesthetized guinea-pigs induced electrocardiographic changes (auriculo-ventricular and intraventricular conduction lenghthening, bradycardia, QRS axis and T axis rotations) quite identical to those induced by imipramine. However they appeared later and mianserin produced cardiac arrest at higher dose (133 mg/kg) than did imipramine (73 mg/kg). In vitro, increasing concentrations of mianserin suppressed the electrical response of stimulated, isolated ventricular heart strips, but this suppression was obtained by a higher concentration (172 micrograms/ml) than with imipramine (80 micrograms/ml). Transmembrane potentials were not affected by a 5 or 10 micrograms/ml mianserin or a 5 micrograms/ml imipramine perfusion. With 20 micrograms/ml mianserin or 10 micrograms/ml imipramine, only a reduced duration of the action potential was obtained. With 50 micrograms/ml mianserin or 20 micrograms/ml imipramine, the resting potential was reduced. However, with imipramine only it was preceded by a decrease in the maximal velocity of depolarisation. These results show that mianserin induces transmembrane permeability changes which appear to differ from and to be less marked than those induced by imipramine. Molar sodium bicarbonate reversed in vivo and in vitro the electrophysiologic changes elicited either by mianserin or by imipramine, but with mianserin the transient improvement was followed by an aggravation of the cardiac troubles.