Prevention of tricyclic antidepressant-induced ventricular tachyarrhythmia by a specific bradycardic agent in a canine model.
Sinus tachycardia facilitates ventricular conduction delay and sustained ventricular tachyarrhythmias during tricyclic antidepressant overdose. We hypothesized that impeding sinus tachycardia with the specific bradycardia agent, UL-FS 49, would reduce the incidence of ventricular tachyarrhythmia caused by tricyclic antidepressant overdose and tested this hypothesis in a canine model of ventricular tachycardia (VT) induced by graded amitriptyline infusion (0.5-1.0 mg/kg/min) during continuous hemodynamic monitoring. Three groups were studied. A control group (group A, n = 8) received amitriptyline infusion alone. A pretreated group (group B, n = 8) received UL-FS 49 (1 mg/kg intravenously, i.v.) 45 minutes before amitriptyline infusion. A treatment group (group C, n = 5) received UL-FS 49 (1 mg/kg) during amitriptyline infusion after onset of ventricular tachyarrhythmia. Seven (88%) in group A had ventricular tachyarrhythmia at 35 +/- 6 min of amitriptyline infusion. Ventricular tachyarrhythmia did not occur in any (0%) animal in group B. Peak sinus heart rate (HR) was significantly higher in group A (160.0 +/- 9.8 beats/min) than in group B (92.8 +/- 5.3 beats/min; p < 0.0001). Unimpeded sinus tachycardia in group A was associated with a significantly longer QRS duration (158.8 +/- 7.4 ms) as compared with group B (101.0 +/- 2.3 ms; p < 0.0001). UL-FS 49 did not influence systolic blood pressure (SBP) at baseline or during amitriptyline infusion. In group C, 3 of 5 dogs with nonsustained VT (NSVT) had effective sinus rate slowing and suppression of all NSVT after UL-FS 49. UL-FS 49 did not terminate SVT in 2 of 5 group C dogs.(ABSTRACT TRUNCATED AT 250 WORDS)
Ansel
G M
GM
Division of Cardiology, Ohio State University Hospitals, Columbus 43210.
Meimer
J P
JP
Nelson
S D
SD
D000639:Amitriptyline / Q000506:poisoning*; D000818:Animals; D001552:Benzazepines / Q000627:therapeutic use*; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D004285:Dogs; D004562:Electrocardiography; D005260:Female; D008297:Male; D017180:Tachycardia, Ventricular / Q000139:chemically induced / Q000517:prevention & control*
D001552:Benzazepines; D002317:Cardiovascular Agents; D000639:Amitriptyline; C043636:zatebradine