The effects of thioridazine on electrical and ischemic ventricular fibrillation in the dog heart in situ.
Lethal ventricular arrhythmias have occurred in patients taking thioridazine. Therefore, we studied two canine models to determine if thioridazine alters vulnerability to ventricular fibrillation. In 30 chloralose-anesthetized dogs, the repetitive response threshold was used to assess vulnerability during right ventricular stimulation with transvenous catheter electrodes. Placebo, 10 mg/kg of thioridazine (therapeutic dose) or 30 mg/kg of thioridazine (high dose) was infused i.v. (n = 10 each group). Repetitive response threshold, diastolic excitability, QRS, Q-Tc and plasma thioridazine concentrations were measured before and after drug. Both 10 and 30 mg/kg of thioridazine increased diastolic excitability threshold (P < .05) while only the 30 mg/kg dose widened QRS (P < .05) and prolonged Q-Tc (P < .05). RRT was unchanged. In 45 pentobarbital-anesthetized dogs, one stage ligation of the left anterior descending coronary artery was performed after pretreatment with placebo, 10 or 30 mg/kg of thioridazine (n = 15 each group). Spontaneous ventricular fibrillation occurred in 6 of 15 dogs (40%) after placebo, 8 of 15 dogs (53%) after 10 mg/kg of thioridazine and 14 of 15 dogs (93%) after 30 mg/ kg of thioridazine. Although thioridazine depressed excitability and had no effect on electrical fibrillation threshold, the 30 mg/kg dose increased the likelihood of spontaneous ventricular fibrillation during acute ischemia.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003331:Coronary Vessels / Q000502:physiology; D004285:Dogs; D004558:Electric Stimulation; D004562:Electrocardiography; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007511:Ischemia / Q000150:complications; D008297:Male; D011188:Potassium / Q000097:blood; D013881:Thioridazine / Q000633:toxicity*; D014693:Ventricular Fibrillation / Q000139:chemically induced* / Q000209:etiology / Q000503:physiopathology
D013881:Thioridazine; D011188:Potassium