Effect of sertraline on ouabain-induced arrhythmia in isolated guinea-pig atria

Abstract

The effect of sertraline a selective serotonin reuptake inhibitor antidepressant was studied on ouabain-induced toxicity (arrhythmia) in spontaneously beating isolated guinea-pig atria. The guinea-pig atrium was dissected out and suspended in modified Krebs solution under physiological conditions. Drugs were added into solutions. The changes in rate and force of contractions were measured using a physiograph. Sertraline (2-16 microg/mL) caused a dose-dependent decrease in the rate of contractions (17-46%) and in the contractile force (26-48%). Ouabain alone (1.2 microg/mL) produced arrhythmia at 7.8 min and asystole at 22 min. Pre- administration of the atria with sertraline (8 microg/mL) significantly increased the time required to produce arrhythmia by ouabain to 20.5 min, prolonged the beating of atria to more than 64.5 min and delayed the occurrence of asystolia. The pattern of contractile force induced by sertraline + ouabain was more regular than that produced by ouabain alone. These findings indicate that sertraline produces direct cardiac action, probably due to the inhibition of cardiac Na(+) and Ca(2+) channels. Our results suggest that sertraline may reduce the membrane conduction through inhibition of ionic channels which decrease ouabain-induced arrhythmia.