The effect of Fluoxetine on Ouabain-induced toxicity in isolated atrium of guinea pig

Abstract

History and Objectives: Fluoxetine is an anti-depressant drug that specifically inhibits serotonin re-uptake. Since fluoxetine can lead to bradycardia and may have pro-arrhythmic and anti-arrhythmic properties, this study was carried out to evaluate the effect of fluoxetine on ouabain-induced arrhythmia in isolated atrium of Guinea pig. Materials and Methods: In this study, Guinea pigs from both sexes (350-600 g) were used. The animal’s atrium was totally isolated from the ventricle. Thirty-two isolated atria were studied in 4 groups, that is, control, fluoxetine, ouabain and ouabain in combination with fluoxetine. The isolated atria were inserted into modified Oxygenated Krebs solution. Therefore, the mentioned drugs were added to the bath and 20 min later, ionic content of the tissue was measured. Results: Fluoxetine (2-16 µg) can produce a short increase in contractile force (4 min), but finally decrease force and rate of isolated atrium. Ouabain (1.2 µg/ml) can lead to atrial arrhythmic after 1.5 min and after 16 min leads to total toxicity, asystole and atrial cease. Fluoxetine pretreatment (4 µg/ml) can delay the occurrence of arrhythmia up to 5 min (P<0.05). Meanwhile, survival time for atrium increased to greater than 40 min (P<0.05). Ionic measurement of atrial tissue showed that ouabain by itself can increase the level of sodium, but no such effect on potassium and calcium levels. In addition, fluoxetine in itself can significantly increase potassium level (P<0.05). Administration of fluoxetine and therefore, ouabain can attenuate the toxic effect of ouabain on ionic changes and even return it to normal level. Conclusion and Recommendations: It is concluded that fluoxetine has a direct negative inotropic and chronotropic effect on isolated atrium as a possible result of inhibition of sodium and calcium channels and it can probably prevent ouabain-induced toxicity and arrhythmia in atrium of Guinea pig through stabilization of cell membrane and/or prevention of ionic changes that is a quinidine-like effect