Tricyclic antidepressants directly depress human myocardial mechanical function independent of effects on the conduction system

Objectives: To measure the effect of tricyclic antidepressant drugs (TCAs) on human myocardial contractility. Methods: Human atrial tissue was obtaine d during cardiac bypass surgery. The tissue was harvested, suspended in a T yrode buffer at 37 degreesC, and perfused with a 95%/5% oxygen-carbon dioxi de mixture. Developed force was continuously measured using a force transdu cer and recorded by computer. After an equilibration period, escalating dos es of amitriptyline or desipramine were added to the bath. All strips were exposed to the following five concentrations of each drug: 0 (control) 0.4, 4, 40, and 400 muM. The results for each experiment were expressed as the difference between the developed force measured prior to the addition of ea ch concentration of drug and the developed force measured after a 30-minute exposure to the drug. Results: Desipramine decreased the developed force b y 27%, 49%, and 74% at concentrations of 0.4, 40, and 400 muM, respectively . Amitriptyline decreased the developed force by 38% at the 40-muM concentr ation and by 89% at the 400-muM concentration. Untreated strips retained 94 % of baseline developed force at 150 minutes. Conclusions: Tricyclic antide pressants depress human myocardial function in a dose-dependent fashion ind ependent of the effects on the cardiac conduction system. While previous wo rk has demonstrated the effect of therapies for the reversal of impaired ca rdiac conduction following TCA poisoning, to the best of the authors' knowl edge, no reports have documented the effects of therapy on direct myocardia l depression. Additional therapies targeted at reversing the direct cardiod epressive effects of TCA may improve outcome following TCA poisoning.