Abstracts

Rationale: Status epilepticus (SE), which is a period of protracted seizure activity, produces lasting autonomic abnormalities, lethal cardiac effects, and increased risk of mortality in both patients and animals. Albeit, the mechanisms that increase mortality are unknown, accumulating evidence suggests that excessive stimulation of the sympathetic nervous system (SymNS) during SE contributes to cardiac dysfunction. Neurogenically mediated cardiac stunning is a reversible deficit in cardiac pumping efficiency that can result from adrenoceptor overstimulation by the SymNS. We previously observed cardiac myocyte damage and altered electrical activity of the heart in an animal model of SE. However, functional deficits in cardiac performance after SE have not been previously reported in animals. These studies were designed to determine if self-sustaining limbic status epilepticus (SSLSE) in rats produces cardiac stunning, which is mediated by the SymNS. Methods: SSLSE was induced in male, Sprague-Dawley rats by electrical stimulation of the left amygdala for 40min. After the first stage 4 (Racine Scale) seizure, rats were divided into 2 groups and administered either saline (SE-Sal) or the peripherally acting, ?-1 adrenergic antagonist atenolol (SE-AT; iv, 1mg/kg) that maintained heart rates at pre-seizure levels. SSLSE was terminated after 90 min by valproic acid (ip, 400mg/kg). Control (Cont) rats received similar treatments at concurrent time points, but no electrical stimulation. Following 24hr, rats were anesthetized with urethane (ip, 1.2mg/kg), and implanted with electrodes to record electrocardiographs (ECG), and a catheter in the right carotid artery to measure mean arterial pressure (MAP) and left ventricular performance. QT interval, corrected for heart rate (QTc; Bazett s formula), and dispersion (QTcd) were calculated from the ECG. Cardiac output (CO) was measured by thermodilution. MAP and left ventricular pulse pressures (LVPP) were recorded from the catheter in the aortic arch and ventricle, respectively. LVPP was used to determine ventricular performance by calculating the change in left ventricular max pressure divided by the change in time (dP/dt max). Results: In SE-Sal animals, CO and left ventricular dP/dt max were significantly decreased, while MAP, QTc, and QTcd were increased when compared with SE-AT and Cont rats 24 hr after seizures. There was no significant difference in heart rate in any group 24hr following SE. Conclusions: These studies demonstrate diminished cardiac ventricular function in a rat model of SE that is consistent with SE in humans. Further, these studies show that administration of the ?-1 receptor antagonist AT during SSLSE prevents the development of cardiac contractile dysfunctions within 24hr of SE. Finally, these data are consistent with the hypothesis that during SE high levels of plasma catecholamines induce adrenoceptor over-stimulation producing cardiac stunning. Together these results provide a therapeutic strategy for the prevention of adverse cardiac effects caused by SE, which may reduce the risk of death.