Effects of antidepressants on the intraventricular conduction and the incidence of arrhythmias induced by programmed ventricular stimulation in the dog heart after myocardial infarction.
The effects of mianserin, a tetracyclic antidepressant, and adinazolam, a new triazolobenzodiazepine which has antidepressant activity, on intraventricular conduction and the incidence of arrhythmias induced by programmed ventricular stimulation were studied in the dog heart after myocardial infarction and compared to the effects of amitriptyline, a standard tricyclic antidepressant. Amitriptyline at a dose of 1 mg/kg significantly slowed ventricular conduction in a frequency-dependent manner and at doses of 2 and 3 mg/kg significantly slowed ventricular conduction in infarcted ventricular myocardium. Amitriptyline also significantly slowed ventricular conduction in normal myocardium. Amitriptyline increased the incidence of ventricular arrhythmias induced by the programmed ventricular stimulation and prolonged the intraventricular delayed conduction resulting in re-entrant ventricular arrhythmia. On the other hand, mianserin and adinazolam at doses of 1-3 mg/kg had no significant effects on intraventricular conduction in infarcted and normal myocardium and on the incidence of arrhythmias induced by programmed ventricular stimulation. From these results, we can expect that mianserin and adinazolam may have a much lower cardiac toxicity than amitriptyline.
Nishimoto
M
M
Department of Pharmacology, Hamamatsu University School of Medicine, Japan.
Hashimoto
H
H
Ozaki
T
T
Nagashima
S
S
Nakashima
M
M
D000639:Amitriptyline / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000503:physiopathology; D001569:Benzodiazepines / Q000494:pharmacology; D004285:Dogs; D004558:Electric Stimulation; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006329:Heart Conduction System / Q000187:drug effects*; D008803:Mianserin / Q000494:pharmacology; D009203:Myocardial Infarction / Q000503:physiopathology*
D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D001569:Benzodiazepines; D000639:Amitriptyline; D008803:Mianserin; C039668:adinazolam