Effects of dothiepin on delayed conduction produced by ventricular arrhythmia in the canine heart after myocardial infarction.
1. In order to clarify the arrhythmogenic effects of antidepressants, the authors examined the effects of dothiepin and amitriptyline on the ventricular activation time (VAT), effective refractory periods(ERP) and incidence of arrhythmias induced by programmed electrical stimulation(PES) in the dog heart in situ after myocardial infarction. 2. Myocardial infarction was produced by two-stage ligation of the left anterior descending coronary artery. Seven days after ligation, bipolar electrodes were sutured on the ventricular surface of the infarcted and normal zones to apply an electrical stimulation or record ventricular activation. An electrical stimulation with coupling interval 250 or 180 ms was applied on the ventricular surface, and AT was measured. 3. Dothiepin at doses of 1-3 mg/kg increased the heart rate. The VAT of coupling interval 180 ms in the infarcted zone was increased by the administration of 3 mg/kg dosulepin. Dothiepin at 3 mg/kg increased the incidence of ventricular arrhythmias induced by PES. 4. Amitriptyline, at doses of 1-3 mg/kg, significantly increased the heart rate. Amitriptyline increased the VAT dose- and frequency-dependently(2,3 mg/kg zone), and prolonged the ERP and QT c interval. Amitriptyline at doses of 1-3 mg/kg increased the incidence of ventricular arrhythmias by PES. 5. These results indicate that dothiepin, 1-3 mg/kg, has lesser effects on cardiac delayed conduction produced by ventricular arrhythmia than amitriptyline.
Nishimoto
M
M
Department of Clinical Pharmacology, Hamamatsu University School of Medicine, Japan.
Hashimoto
H
H
Ikeda
Y
Y
Umemura
K
K
Nakashima
M
M
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects* / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004308:Dothiepin / Q000009:adverse effects* / Q000494:pharmacology; D004558:Electric Stimulation; D006339:Heart Rate / Q000187:drug effects*; D009203:Myocardial Infarction / Q000503:physiopathology* / Q000662:veterinary; D016276:Ventricular Function / Q000187:drug effects
D000929:Antidepressive Agents, Tricyclic; D004308:Dothiepin