Antidepressants Cause Bradycardia and Heart Block in GD 13 Rat Embryos In Vitro

Abstract

This study investigated the effects of a range of antidepressant drugs on the heart of gestation day 13 rat embryos in vitro. The general hypothesis was that the drugs would adversely affect the function of the embryonic heart since they all have some cardiac ion channel blocking activity in addition to their main pharmacological effect on neurotransmitters. The results showed that all the tested drugs caused bradycardia in a generally concentration-dependent manner. At higher concentrations most of the drugs caused some degree of heart block consistent with sodium channel blockade and some drugs also showed negative inotropy associated with blockade of the L-type calcium channel. One drug, trazodone, caused arrhythmia consistent with blockade of the hERG (human ether-a-go-go related gene) potassium channel. In general the effects on the embryonic rat heart were only seen at "free drug" concentrations much greater than those likely to occur in pregnant women taking antidepressant medication. The least margin of safety was seen with the tricyclic antidepressants and the serotonin antagonist and reuptake inhibitor trazodone.

Effects of Macrolide Antibiotics on Rat Embryonic Heart Function In Vitro

“…As in previously published studies (Abela et al., ; Nilsson et al., , ; Ababneh et al., ; Gunnstrom et al., ), the video recordings of the embryonic hearts were examined and analyzed using software developed at the University of Uppsala (Khan et al., ; Khan Niazi et al, 2011). In this software, the atria and ventricles of the heart are identified on the video image and are manually marked.…”

“…Following previous published studies (Abela et al, 2010;Nilsson et al, 2010;Ababneh et al, 2012;Gunnstrom et al, 2012;Nilsson et al, 2013), the pregnant dams were killed on GD 13 by CO 2 inhalation and the embryos were prepared for culture. The uterus was removed and placed in warm (37°C) phosphate-buffered saline.…”

A comparison of drug-induced cardiotoxicity in rat embryos cultured in human serum or protein free media

“…The concentrations to be tested for the other drugs were selected from previous publications as concentrations that caused a significant reduction in heart rate when the drug was administered in DMEM (Ababneh et al, 2011;Abela et al, 2010;Gunnstrom et al, 2012).…”

“…In this assay, whole rat embryos are exposed to therapeutic drugs with ion channel blocking properties and the effect on the function on the embryonic heart is observed and recorded (Ababneh, Ritchie, & Webster, 2011;Abela et al, 2010;Gunnstrom, Ababneh, Webster, Oakes, & Ritchie, 2012). The impetus for these studies is that many therapeutic drugs block ion channels, sometimes as a desired therapeutic effect or as an unwanted side-effect.…”

“…All the tested drugs blocked hERG potassium and/or sodium ion channels (not necessarily as their therapeutic effect) and caused a concentration-dependent bradycardia in the rat embryonic heart (Ababneh et al, 2011;Abela et al, 2005;Gunnstrom et al, 2012). For each drug we determined the concentration that caused severe bradycardia down to the no-effect concentration.…”