title: The effects of thioridazine on electrical and ischemic ventricular fibrillation in the dog heart in situ.
abstract: 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.
mesh_terms: 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
chemical_list: D013881:Thioridazine; D011188:Potassium