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 phenyoin 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 μg/ml) caused a dose-dependent decrease in contractile force of isolated guinea-pig atria (9-120%, p<0.001), but no change on the rate of contractions. Ouabain alone (1.2 μg/ml) produced arrhythmia at 10 min and asystole at 21 min. Pretreatment with SV (200 μg/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.