Abstracts

Rationale: Sympathetic predominance represents a potential mechanism underlying cardiac remodeling in epilepsy. In acquired epilepsy models in which initial status epilepticus (SE) is followed by recurrent seizures (epilepsy) later in life, longer corrected QT interval (QTc) duration and higher beat-to-beat QTc interval variability have been described under conditions of sympathetic predominance at 2 weeks following SE, a period that corresponds to epileptogenesis. In this study we sought to examine whether attenuating sympathetic nervous system activities following SE will ameliorate these early ventricular abnormalities associated with epilepsy. Methods: We induced SE in male Sprague-Dawley rats by administrating intraperitoneal kainate (15mg/kg). Following SE, the animals were fed with standard chow (n=13) or chow containing atenolol (n=14) for 2 weeks. As control, sham rats were also fed either standard chow or atenolol-containing chow (n=12/group). We obtained electrocardiographic (ECG) recordings at 2 weeks following SE. In addition to standard ECG parameters (heart rate, PR, QRS, and QTc intervals), we measured 10 consecutive QT and RR intervals per ECG. Beat-to-beat QTc interval variability was calculated as (Σ|QTcn+1 - QTcn|)/(N x √2), where |QTcn+1 - QTcn| is the absolute difference between the 2 successive beats and N is number of heartbeats. Data were analyzed using ANOVA with post hoc Tukey and expressed as mean±SEM. Results: Atenolol treated sham and SE rats consumed 14.6 ± 0.5mg/kg/day of atenolol. Sham-vehicle and sham-atenolol groups exhibited comparable QTc interval duration and variability. In contrast, compared with the sham-vehicle group, SE-vehicle rats exhibited longer QTc interval (224.2 ± 5.2 ms vs. 260.8 ± 7.5 ms, sham-vehicle vs. SE-vehicle, p < 0.01) and higher variability (9.4 ± 1.1 ms vs. 17.2 ± 1.7 ms, sham-vehicle vs. SE-vehicle, p < 0.01). Atenolol treatment in the SE rats for 2 weeks decreased QTc interval duration (260.8 ± 7.5 ms vs. 217.2 ± 6.1 ms, SE-vehicle vs. SE-atenolol, p < 0.001) and variability (17.2 ± 1.7 ms vs. 12.1 ± 1.3, SE-vehicle vs. SE-atenolol, p < 0.05). Conclusions: Our findings suggest that sympathetic nervous system activities following SE contributes to early ventricular repolarization abnormalities in this acquired epilepsy model. Therefore, attenuating sympathetic nervous system activities may be a potential therapeutic target for the prevention of cardiac remodeling associated with epilepsy. Funding: R01NS081053; K08NS063117