Cardiotoxicity of tricyclic antidepressants in primary cultures of rat myocardial cells

Abstract

Primary cultures of myocardial cells were used to evaluate the cardiotoxic potential of various tricyclic antidepressants (TCA). Lactate dehydrogenase (LDH) leakage, cellular viability and beating rates were measured to compare the cardiotoxicity of amitriptyline, desipramine, imipramine and nortriptyline. TCA were added to the cultures to give final concentrations of 1 .times. 10-5, 1 .times. 10-4 and 1 .times. 10-3 M. Treatments lasted 1 and 4 h. All TCA caused significant release of LDH and decreased cellular viability when added at 1 .times. 10-3 M for 1 and 4 h. Amitriptyline was the only compound that caused significant LDH release 4 h after exposure to lower doses. Decreased viability was observed 4 h after exposure to all TCA at 1 .times. 10-4 and 1 .times. 10-3 M. Arrhythmias were observed 1 h after exposure to 1 .times. 10-5 and 1 .times. 10-4 M amitriptyline. All doses of amitriptyline inhibited beating 4 h after exposure. Imipramine, desipramine and nortriptyline at 1 .times. 10-5 M decreased the beating rates of cultured myocytes 1 and 4 h after exposure. Arrhythmias and/or total inhibition of beating were observed when the cultures were exposed to higher concentrations of these compounds. Based on these data, the rank order of cardiotoxicity was amitriptyline > imipramine = desipramine > nortriptyline.