Abstracts

RATIONALE: Generalized seizures are associated with autonomic dysfunction that may cause cardiac arrhythmias. We have described a narrow QRS complex cardiac arrhythmia that occurs during the immediate post-ictal period following MES-induced seizures in the rat. The severe irregularity of R-R intervals during the arrhythmia suggests it is mediated by autonomic abnormalities. To test this hypothesis, we studied the effects of atropine or propranolol pretreatment on the duration of arrhythmias evoked by MES-induced seizures in freely-moving rats.
METHODS: Sprague-Dawley rats (n=4 per group) were implanted with EEG and EKG electrodes under general anesthesia. One week later, rats were treated with either saline solution (1 ml/kg, i.p.), or atropine methylbromide (10 mg/kg, i.p.), or propranolol (10 mg/kg, i.p.), and fifteen minutes later, seizures were induced with MES (50 mA x 500 Hz x 0.3 sec) using earclips. The duration of arrhythmia was determined visually on the EKG trace. Nonparameteric (Friedman[scquote]s) testing was used to determine statistically significant changes in treated groups over saline-treated control animals.
RESULTS: In control animals, median seizure duration was 38.0 sec [plusminus]1.3; (SD). Pre-treatment with atropine (10 mg/kg; n=4) suppressed MES-evoked arrhythmia in all animals (P[lt]0.05). In contrast, propanolol (10 mg/kg; n=4) reduced arrhythmia duration by 50 % compared to control rats (22.0 sec [plusminus]1.3; P[lt]0.05).
CONCLUSIONS: Our data implicate the participation of both parasympathetic and sympathetic mechanisms in MES seizure-evoked arrhythmias. The elimination of arrhythmia by atropine methylbromide suggests that vagal activity may mediate seizure-induced arrhythmias. Further characterization of the neural mechanisms involved may help to identify therapies to prevent seizure-induced arrhythmias and potentially, sudden unexplained death in epilepsy (SUDEP).
Support: Southern Illinois University Central Research Committee