Abstracts

Rationale: Sudden unexpected death in epilepsy (SUDEP) is a devastating complication of drug-resistant epilepsy. Several mechanisms may contribute to SUDEP including sudden cardiac death. We have previously found decreased Kv4 potassium channel levels in the myocardium of epileptic rats. In this study we sought to determine whether there was an associated alteration in sympathetic drive and in myocardial excitability, thereby posing a risk for sudden death in this model. Indeed, previous work by others has shown that in primary cardiac pathology, alteration in myocardial Kv4 channels is associated with action potential prolongation and lethal arrhythmia. Methods: Surface electrocardiograms (EKG) were obtained in sham and piloparpine-induced 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. Atenolol (10mg/kg/day, i.p.) and vehicle were given to a subgroup of sham and epileptic rats for 1wk (n=4/group). Pre- and post-treatment EKG was obtained and HR, PR, QRS and QTc intervals were measured. Results: Epileptic rats exhibited increased resting HR compared with sham (273 16.5 vs. 238 3.6 beats/min, p<0.05). Compared with sham, epileptic rats also exhibited prolonged QRS (89 5 vs. 73 5 msec, p<0,05) and QTc (336 11 vs. 289 11 msec, p<0.01) intervals. Optical mapping showed slower conduction velocity (0.44m/s vs. 0.74m/s) in hearts from epileptic compared to sham rats. Stimulation induced ectopic beats in the epileptic but not in the sham heart preparation. In the epileptic rats, atenolol did not significantly lower HR (333 42 vs. 275 39.1 beats/min, pre vs. post atenolol, p=0.08), but the QTc was normalized (298 8 vs. 269 7 msec, p<0.05).