Myometrium contractility in epilepsy and effect of antiepileptics on contractility of myometrium isolated from wag/rij epileptic rats

Whether myometrial contractility in epilepsy is different from healthy individuals and anti-epileptics (AEDs) have a direct influence on the contractility and thereby may lead to obstetrical complications beyond the concerned fetal neurodevelopmental impairments, remains unclear. Hence we isolated myometrial strips from both non-pregnant and pregnant absence epileptic WAG/Rij and control Wistar rats and investigated contractility, through comparison of the spontaneous contractility and responses to oxytocin (OT), and possible effects of phenytoin, levetiracetam and valproic acid alone and in combination on OT-induced contractions. Myometrial strips were removed from WAG/Rij and Wistar rats and placed in an organ bath and isometric contractions were recorded. After adaptation, developed spontaneous contractions were evaluated and contractions were stimulated by OT. The effects of cumulative concentrations of the selected AEDs including phenytoin, valproic acid and levetiracetam on area under the curve (AUC), amplitude and frequency of contractions were evaluated by 10-minute periods. Data were analyzed using one-way ANOVA and Tukey HSD test. As a result, spontaneous contractility and responses to OT showed species difference: spontaneous contractility of non-pregnant WAG/Rij preparations was significantly higher and upon stimulation with OT WAG/Rij myometrium showed significantly lower sensitivity, compared with preparations from Wistars (p<0.01). Phenytoin and valproic acid caused a concentration-dependent significant attenuation (p<0.05) in spontaneous and OT-induced contractions of myometrium from WAG/Rij and Wistar rats, both non-pregnant and pregnant. Levetiracetam did not cause significant inhibition despite higher than clinically relevant concentrations. Key Words: Antiepileptic Drugs, Experimental animal model, Epilepsy, Myometrial contraction