effect of sodium valproate on ouabain-induced arrhythmia in isolated guinea-pig atria

sodium valproate (sv), an antiepileptic drug has several mechanism of action. it inhibits voltage sensitive na+ channels and reduces intracellular na accumulation. these actions are similar to that of both phenytoin and carbamazepine. we have investigated the direct cardiac action of sv and its effects on ouabain-induced arrhythmia in isolated guinea-pig atria. the guinea-pig atrium was dissected out and suspended in modified krebs solution under physiologic conditions. drug was added into the solution. the changes in rate and contractions were measured using a physiograph. sv (100-300 µ g/ml) caused a dose-dependent decrease in contractile force of isolated guinea-pig atria (9-120%, p<0.001), but not any change on the rate of contractions. ouabain alone (1.2 µ g/ml) produced arrhythmia at 10 min and asystole at 21 min. pretreatment with sv (200µg/ml) significantly increased time of onset of arrhythmia to 29 min and asystole to more than 38 min. sv may have a direct  cardiac effect to reduce the membrane conductance through ion channels which may decrease ouabain toxicity in isolated guinea-pig atria.