The effect of C1 spinal cord transection or bilateral adrenal vein ligation on thioridazine-induced arrhythmia and death in the cat.
The phenothiazine thioridazine 1 mg/kg/min was infused intravenously into three groups of cats: (1) thioridazine alone (N = 5), (2) after bilateral adrenal ligation (N = 4), and (3) after spinal cord section at the atlanto-occipital junction (C1; N = 6). The times to arrhythmia and death with thioridazine alone were 47.8 +/- 7.8 and 72.8 +/- 5.6 minutes respectively. After bilateral adrenal ligation, arrhythmia and death occurred at 41.1 +/- 5.2 and 53.1 +/- 5.8 minutes, respectively, which showed no increase (P greater than .05) from thioridazine alone. After spinal cord section, thioridazine-induced arrhythmia and death occurred at 74.0 +/- 13.7 and 85.7 +/- 13.8 minutes, respectively, which were not increased (P greater than .05) when compared with thioridazine alone. The results of this study suggest that neither adrenomedullary catecholamines nor the central sympathetic component above C1 plays a significant role in acute thioridazine-induced arrhythmia. The action of thioridazine to induce arrhythmia in spite of transection of the spinal cord or bilateral adrenal vein ligation suggests that its cardiotoxicity is a result of a direct myocardial effect. Thioridazine depressed blood pressure without producing the sustained reflex tachycardia normally seen with hypotension. This suggests that the agent may modify the baroreceptor reflex arc.
D000313:Adrenal Medulla / Q000098:blood supply / Q000503:physiopathology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000502:physiology; D002415:Cats; D002490:Central Nervous System / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008026:Ligation; D008297:Male; D013116:Spinal Cord / Q000601:surgery; D013564:Sympathetic Nervous System / Q000503:physiopathology; D013881:Thioridazine / Q000633:toxicity*; D013997:Time Factors; D014680:Veins
D002395:Catecholamines; D013881:Thioridazine