Comparison of the cardiac electrophysiologic effects of amitriptyline and clomipramine in the dog after myocardial infarction.
The effects of the tricyclic antidepressants amitriptyline and clomipramine on intraventricular conduction, effective refractory period and incidence of ventricular arrhythmias induced by programmed stimulation, were studied in the dog heart after myocardial infarction. Amitriptyline, at doses of 1 to 3 mg/kg, significantly slowed ventricular conduction of the infarcted zones in a frequency-dependent and a dose-dependent manner. Amitriptyline, at doses of 2 and 3 mg/kg, slightly slowed conduction in normal zones. The effective refractory period was prolonged by amitriptyline at a dose of 2 mg/kg. Amitriptyline increased the incidence of ventricular arrhythmias induced by programmed stimulation. On the other hand, the depressant effect of clomipramine, at doses of 1 to 3 mg/kg, on the conduction of infarcted zones was lower than that of amitriptyline, whereas the severely depressed conduction in the infarcted zone was obviously slowed by clomipramine. The incidence of ventricular arrhythmias did not significantly increase with clomipramine. From the present results, clomipramine seems to have a lower cardiac toxicity than amitriptyline, although clomipramine produces a slight depression of conduction in infarcted zones.
Hashimoto
H
H
Department of Pharmacology, Hamamatsu University School of Medicine, Japan.
Nishimoto
M
M
Ozaki
T
T
Ohara
K
K
Nakashima
M
M
D000639:Amitriptyline / Q000494:pharmacology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D002997:Clomipramine / Q000494:pharmacology*; D004285:Dogs; D004558:Electric Stimulation; D004562:Electrocardiography; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology; D012032:Refractory Period, Electrophysiological / Q000187:drug effects
D000639:Amitriptyline; D002997:Clomipramine