In vitrocardiac safety assessment of antidepressant drugs in intact rat hearts and after ischemia-reperfusion

Burcak Deniz Dedeoglu, Oner Suzer
Istanbul University, Cerrahpasa Faculty of Medicine, Dept. of Pharmacology and Clinical Pharmacology, Istanbul, Turkey

In this study different noradrenalin and serotonin reuptake inhibitor antidepressant drugs were used. Their dose dependent effects on isolated hearts were compared with increasing concentrations in intact hearts and following ischemia-reperfusion in order to get cardiac safety profile data. The animals were divided in to nine groups of six rats each. The hearts were perfused in Langendorff systems. In intact groups, after a stabilisation period, six different concentrations (1×10-7 to 1×10-4.5mol/L) for amitriptyline, fluoxetine, maprotiline, and trazodone were applied for five minutes in increasing concentrations. For ischemia-reperfusion experiments the hearts were subjected to normothermic global ischemia for 15 minutes where the hearts were kept in hypoxic normothermic Tyrode solution. The hearts were then reperfused for 30 minutes before drug application in the same setting as intact hearts. Haemodynamic variables and bipolar electrocardiograms were recorded continuously. Amitriptyline, fluoxetine and maprotiline depressed left ventricular developed pressure (respectively 8.3±6.9; 26.7±10.3 and 65.2±25.0% of baseline value for normoxic experiments; 15.1±4.7; 14.3±5.3 and 13.6±4.1% of baseline for ischemia-reperfusion experiments at the highest concentration) and +dp/dtmax in a dose dependent manner, whereas the depression was moderate with trazodone (left ventricular developed pressure values; 94.0±5.0; 59.5±10.4% of baseline respectively for normoxic and ischemia reperfusion groups), in both normoxic and ischemia reperfusion groups. All drugs decreased heart rate in higher concentrations. In conclusion trazodone seems to be a safer agent in this setting regarding all parameters measured.