Abstracts

Rationale: Epilepsy is associated with significant morbidity and mortality. Many pathological mechanisms possibly contribute including sudden cardiac death, which can result from arrhythmias. Alternatively, altered cardiac structure and function leading to impaired cardiac output could result in death. Increasing evidence suggest that alterations in the autonomic nervous system and subtle electrocardiogram (EKG) changes are associated with epilepsy in human and animals models, which could increase susceptibility to arrhythmia and sudden death. In these studies we evaluated sudden death, altered cardiac structure and function, and arrhythmia in a model of temporal lobe epilepsy.Methods: SE was induced using pilocarpine (300mg/kg, i.p.) in male Sprague-Dawley rats. Cardiac MRI was performed in pilocarpine- or vehicle-treated (sham) animals 3wks after SE and prior to the onset of recurrent seizures (n=4) and age-matched sham (n=3). Cardiac ultrasound was performed in rats with established epilepsy (n=3) and age-matched shams (n=3). Indices of cardiac function (ejection fraction, shortening fraction) and structure (ventricular wall and intraventricular septum thickness, ventricular mass) were examined. Surface electrocardiograms (EKG) were obtained in sham and epileptic rats. Heart rates (HR), PR, QRS and QTc intervals were measured (n=15/group). Ex vivo optical mapping of the myocardial action potential was performed in a subset of animals (n=2/group). Conduction velocity, action potential duration and the presence of induced ectopic beats were evaluated.Results: Epileptic rats exhibited a significant decrease in survival with median survival time of 20mo (n=24) compared with 26mo for sham (n=31). Cardiac MRI and ultrasound demonstrated no differences in function and structure between epileptic and age-matched sham animals. Compared with sham, epileptic rats exhibited increased resting HR (273 16.5 v. 238 3.6 beats/min, epileptic v. sham, p<0.05), prolonged QRS (89 5 vs. 73 5 msec, epileptic v. sham, p<0,05) and QTc (336 11 vs. 289 11 msec, epileptic v. sham, p<0.01) intervals. Optical mapping showed slower conduction velocity (0.44m/s vs. 0.74m/s) in hearts from epileptic compared with sham rats. Stimulation induced ectopic beats in the epileptic but not in the sham heart preparation.Conclusions: Under baseline conditions, no discernible differences in cardiac structure and function were observed between epileptic and sham animals. However, subtle alterations of cardiac conduction were observed in epileptic animals as reflected in the surface EKG. Under stimulated conditions, the myocardium of the epileptic rats exhibited increased arrhythomogenicity, likely exacerbated by the underlying conduction abnormalities. Together, these findings recapitulate clinical observations and further support cardiac arrhythmia as a cause for sudden death in individuals with epilepsy. Support: R01NS049427, RO1NS039943, Epilepsy Foundation