Abstracts

Rationale: Status epilepticus (SE) is a devastating neurological insult that frequently leads to sudden death in the period following seizure activity. The mechanism by which prolonged seizures contribute to these deaths is unknown. However, lethal cardiac arrhythmias have been implicated. We propose that SE results in cardiac dysfunction, which increases susceptibility for lethal cardiac arrhythmias. One mechanism which may explain this is sympathetic overstimulation during SE, wherein increased oxygen demand during seizure-induced tachycardia is not met, resulting in cardiac damage and possibly arrhythmogenic cardiac electrical activity. Previous work has shown that SE results in cardiac damage and increased susceptibility to lethal arrhythmias following SE. The present studies were designed to extend these findings by determining if SE produced arrhythmogenic cardiac electrical activity, which might be prevented by beta-blocker therapy, and thereby decrease susceptibility to experimentally induced ventricular arrhythmias. Methods: Two groups of male Spraque-Dawley rats received either Li-pilocarpine, to induce SE, or saline, for controls (Cont). Half of each group was further treated with atenolol (SE-Aten; Cont-Aten), which prevents seizure-induced tachycardia, or saline (SE-Sal;Cont-Sal) every 30 min during SE. 14 days after SE, rats were anesthetized and implanted with subcutaneous electrocardiographic (ECG) electrodes in the chest, and a femoral vein catheter for an infusion of the arrhythmogenic agent aconitine. Changes in cardiac electrical activity were evaluated from 10 min baseline ECG recordings by measuring the mean QT interval, which represents the total time for both ventricular depolarization and repolarization to occur. QT intervals were corrected for variation in heart rate (QTc), and the mean dispersion of QTc (QTcd) was calculated by subtracting the minimum QTc from the maximum QTc. QT interval prolongation is clinically accepted as a prognostic indicator of arrhythmogenic electrical activity of the heart which places patients at risk for arrhythmias. Susceptibility to ventricular arrhythmias was then determined by measuring the latency to the 1st premature ventricular contractions, ventricular tachycardia, and ventricular fibrillation during a 7 min infusion of aconitine (5 µg/Kg/min). Results: Both QTc and QTcd were significantly (p<0.05) longer in SE-Sal (QTc=152±7ms; QTcd=12±1ms) than in SE-Aten (QTc=106±8ms; QTcd=8±1ms), Cont-Sal (QTc=106±9ms; QTcd=8±1ms), and Cont-Aten (QTc=109±3ms; QTcd=9±1ms) rats. Additionally, the latency to all experimentally-induced arrhythmias was shorter in SE-Sal rats than SE-Aten, Cont-Sal, and Cont-Aten animals. Conclusions: These data demonstrate that SE can alter cardiac electrical activity, which increases susceptibility to lethal arrhythmias, and which can be prevented with beta-blocker therapy. These findings support the hypothesis by demonstrating that sympathetic stimulation during seizures increases susceptibility to the arrhythmias which may be a mechanism for sudden death following SE.