Abstract

Amitriptyline (Am) is a frequently prescribed tricyclic antidepressant drug associated with an increased risk of sudden death that has been presumed to be arrhythmia related. Little has been known about the effects of Am on left ventricular function. We studied i.v. Am (0.5, 1.0, and 1.5 mg/kg) in 10 conscious, resting, chronically instrumented dogs. Heart rate (HR) increased up to 70%; this increase was only partially prevented by propranolol. Left ventricular end diastolic pressure (LVEDP) decreased without, but not with, propranolol. Mean arterial pressure (MAP) increased by 10-13% transiently. The maximum rate of rise of left ventricular pressure (dP/dtmax) decreased by 16-18% without propranolol and by 14-29% with propranolol, indicating a moderate decrease in myocardial contractility. Changes in stroke volume were similar to changes in dP/dt. Thus, i.v. Am, at levels similar to therapeutic blood levels, causes a moderate depression of myocardial contractility, which is accentuated by propranolol. Tricyclic antidepressants, therefore, could have adverse effects on cardiac performance in patients with underlying myocardial dysfunction.

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