Abstracts

Rationale: Patients with epilepsy, especially those refractory to antiepileptic medications, have increased risk for sudden unexplained death in epilepsy (SUDEP). Many cases of SUDEP have been linked to altered autonomic control of the heart. However, the precise mechanisms whereby spontaneous seizures affect autonomic control of the cardiovascular system are not fully understood. We hypothesize that chronic spontaneous seizures increase sympathetic nervous system (SymNS) influence over the heart and vasculature, and thereby increase cardiac risk. Methods: Male Sprague-Dawley rats were allowed to develop spontaneous seizures following status epilepticus (SE) induced by intraperitoneal (i.p.) injections of pilocarpine following lithium. Control (Cont) animals did not receive pilocarpine. Following SE, animals were video recorded continusously to monitor development and frequency of spontaneous recurrent seizures (SRS). Immediately following SE, separate groups of Cont and pilocarpine-treated animals were given either a diet containing carbamazepine (CBZ, ≈300 mg/kg/day) or regular rat chow. Subsequently, SRS animals were selected for testing after they developed spontaneous seizures. Other groups (Cont, Cont/CBZ, and SE/CBZ animals) were tested at time points similar to (i.e. number of days post-SE) SRS animals. On the day before testing, rats were implanted with femoral venous and arterial catheters. SRS animals were tested only if at least 4 hr had elapsed since a seizure. Heart rate (HR) and blood pressure (BP), as well as their variability (HRV and BPV, respectively), intrinsic HR (i.e. HR without neural input), baroreflex sensitivity, and cardiac contractility-relaxation dynamics were measured to determine cardiac function and the autonomic contributions to HR. Results: SRS animals exhibited approximately 2-5 seizures/day. CBZ administration prevented the development of seizure activity (<1/day). Baseline HR and cardiac contractility were elevated, while BPV was decreased in SRS animals. These responses are consistent with increased cardiac SymNS tone, and/or decreased vascular SymNS tone. These variables were similar between CBZ-treated SE animal and both groups of Cont rats.