effect of paroxetine on ouabain-induced toxicity in isolated guinea pig atria

ABSTRACT

It has been reported that selective serotonin reuptake inhibitors [SSRIs] possess some cardiac effects. In the present study we have investigated the effect of paroxetine [PX], a potent SSRI agent, on spontaneously as well as ouabain-induced arrhythmia beating isolated guinea-pig atria. The Guinea-pig heart was rapidly removed; the auricles were dissected out in oxygenated modified Krebs solution. The rate and force of spontaneous contractions were recorded isometrically with a photosensitive transducer. PX [1-16 micro g/ml] caused a dose-dependent decrease in the rate of contractions [14-70%] and contractile force [8-16%]. Ouabain alone [1.2 micro g/ml] produced arrhythmia at 7.2 +/- 1.5 min and asystole at 20.1 +/- 3.1 min. Pretreatment with PX [4 micro g/ml] significantly increased the time of arrhythmia onset to 19.8 min. In addition, PX prolonged the duration of action beating from 20.1 +/- 3.1 min to 43.1 +/- 2.6 and delayed the occurrence of asystole. The pattern of contractile force by PX + ouabain treatment was more regular than that observed after administration of ouabain alone. The above findings may the probably be due to the inhibition of cardiac Na[+] and Ca[2+] channels or autonomic nervous system. Results also suggest that PX may reduce the membrane conductance through inhibition of ionic channels to prevent ouabain-induced arrhythmia