Abstracts

Rationale: Sudden unexpected death contributes significantly to mortality in epilepsy. Clinical observations suggest that epilepsy is associated with cardiac manifestations such as resting tachycardia and QTc prolongation. However, the onset of cardiac changes in epilepsy and whether these changes contribute to lethal arrhythmias is not fully investigated. Therefore, we evaluated the onset of cardiac changes and their contribution to ventricular arrhythmias in a model of acquired epilepsy.Methods: Status epilepticus (SE) was induced in the juvenile Sprague-Dawley rats using pilocarpine (300mg/kg, i.p.). Sedated EKG recordings were obtained at various time points following SE. HR, PR, QRS and QT intervals were measured. QTc was calculated using Brazet s formula. In vivo EP studies were performed on age-matched sham and epileptic rats between 7 and 14 mo following SE. Standard EP measurements were obtained after a 10 min acclimatization period under anesthesia. To induce ventricular arrhythmias, pacing was performed at cycle lengths of 100 ms for 8 beats (S1) followed by 1 extra-stimulus (S2) at shorter coupling intervals. An animal was considered to be more susceptible to stimulation-induced arrhythmias if 2 out of 3 trials resulted in ventricular tachycardia (VT). Continuous variables were analyzed using either Student t-test or 2-way ANOVA. Categorical variables were analyzed using the Fisher exact test. The results are expressed in mean SEM.Results: Compared with the age-matched shams, the epileptic rats began to exhibit increased resting HR (271.5 4.4 vs 254.6 3.7 bpm, n=20-21/group, p<0.01) and prolonged QTc (314 7 vs 264 10 ms, n=20-21/group, p<0.01) at 2 mo following SE, coinciding with the appearance of recurrent seizures. The resting tachycardia and QTc prolongation in the epileptic rats were persistent over time. Furthermore, 71% of epileptic rats (10 of 14) developed reproducible VT induced by extra-stimuli whereas only 27% of sham (3 of 11) had inducible VT (p<0.05).Conclusions: There are early and persistent EKG changes in the pilocarpine model of acquired epilepsy. Furthermore, there is an increased susceptibility to ventricular arrhythmias in the epileptic rats. Additional studies are planned to evaluate the role of increased sympathetic tone and the molecular mechanisms underlying these findings in the acquired epilepsy model.