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Abstract

Introduction: Sudden unexpected death in epilepsy (SUDEP) accounts for as high as 30% of epilepsy-related death. Sudden cardiac death from fatal arrhythmias has been proposed as a potential SUDEP mechanism based on the observation that epileptic individuals exhibit resting tachycardia and prolonged QTc. However, whether these changes predispose to stimulation-induced ventricular tachycardia (VT) and whether β blocker, the therapy for VT prevention in long QT syndrome, is effective remain unknown. Methods: We induced status epilepticus (SE) in rats using pilocarpine (300mg/kg, i.p.). Serial EKGs were obtained at various time points following SE. Atenolol (10mg/kg, i.p. bid) or normal saline (NS) were given for 2 d prior to electrophysiological (EP) studies. In vivo EP studies were performed between 7 and 14 mo following SE on the following groups: 1) sham+NS, 2) sham+atenolol, 3) epileptic+NS, 4) epileptic+atenolol. Programmed electrical stimulation (PES) was used to induce VT. An animal was considered to be more susceptible to stimulation-induced arrhythmias if 2 out of 3 trials resulted in VT. Continuous variables were analyzed using Student t-test or 2-way ANOVA. Categorical variables were analyzed using Chi square test. The results are expressed in mean±SEM Results: Compared with the age-matched sham rats, epileptic rats began to exhibit elevated 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. These differences persisted chronically (n=17–18/group, p<0.05). Atenolol decreased HR (12.9 ± 2%, n=6, p<0.01) and shortened QTc (12.7 ± 1.6%, n=6, p<0.01) in the epileptic rats. PES induced VT in 31% sham+NS, 0% sham+atenolol, 65% epileptic+NS and 22% epileptic+atenolol (n=4–17, p<0.05). Conclusions: Cardiac changes are associated with increased stimulation-induced VT suggesting that sudden cardiac death from arrhythmias may contribute to SUDEP. QTc shortening and decreased VT incidence with β blocker in this model suggests a potential therapy in epileptic individuals with prolonged QTc.