Abstracts

Rationale: Status epilepticus (SE) is a devastating neurological insult that frequently leads to sudden death. Deaths do not always occur during or immediately following SE, but within 30 days of the episode. The causes of sudden death are not clear, but lethal ventricular arrhythmias have been implicated. By understanding how SE damages the heart and alters normal cardiac function, cardiovascular therapies may be developed to reduce cardiac morbidity and mortality following SE. Ventricular arrhythmias are well established as a major underlying cause leading to sudden cardiac death, and can result from myocyte damage. Thus, a potential mechanism, and overriding hypothesis by which SE contributes to sudden death is that SE produces myocardial damage and lasting electrical instability in the heart. In addition, our lab has previously shown a decrease in parasympathetic tone 1-2 weeks post-SE, increasing the pro-arrhythmic tendency of the sympathetic nervous system. Therefore, the combination of increased sympathetic influence and cardiac damage caused by SE likely increases the risk of lethal arrhythmias. Although myocyte damage has been reported following severe, uncontrolled SE, the effects of more moderate seizure activity on cardiac tissue, and the susceptibility to arrhythmias have not been investigated. Therefore, we evaluated cardiac damage and susceptibility to ventricular arrhythmias following SE which was terminated at 90 min. Methods: SE was induced in conscious male Sprague-Dawley rats using Li-pilocarpine. The onset of seizure activity was monitored and seizures were ended at 90 min by i.p. injection of valproic acid. Cardiac myocyte damage was estimated by measuring plasma cardiac troponin I levels (TnI) in venous blood sampled 1 and 4 hrs after the initiation of SE. In addition, susceptibility to ventricular arrhythmias was evaluated 14 days after SE by monitoring electrocardiographic (ECG) activity during a 7 min infusion of the arrhythmogenic agent aconitine (5 µg/kg/min i.v.) while under sedation with α-chloralose. The latencies to the onset of premature ventricular contractions, bigeminy, salvo, ventricular tachycardia, and ventricular fibrillation were used as measures of susceptibility to arrhythmias. Rats received ECG implants and vascular catheterization immediately prior to testing. Results: TnI levels were elevated in rats 1 and 4 hrs after the initiation of SE. Furthermore, the latencies to the first premature ventricular contractions, bigeminy, salvo, ventricular tachycardia, and ventricular fibrillation were all decreased in animals 14 days following SE. Conclusions: These studies have demonstrated that SE results in significant cardiac damage within 90 min, which is associated with increased susceptibility to lethal ventricular arrhythmias for at least 14 days following seizure activity in the rat. These results suggest that seizure-induced myocyte injury is a mechanism for mortality during the period following SE.