Abstracts

Rationale: Clinical observations and experimental data suggest that cardiac alterations occur in epilepsy. Studies have shown that epileptic individuals exhibit altered autonomic nervous system input to the heart and intrinsic electrical properties of the heart. These changes are exacerbated during seizures, reflected in the presence of ictal and peri-ictal arrhythmias. Therefore, individuals with drug-resistant epilepsy may have progressive cardiac changes resulting in propensity for fatal arrhythmias. However, little is known regarding the onset and the progression of cardiac manifestation in epilepsy. Animal data suggest that cardiac changes occur early following pilocarpine-induced status epilepticus (SE). However, whether these changes persist during early epileptogenesis remains undefined. Therefore we prospectively investigated cardiac changes in a cohort of epileptic and age-matched sham animals using the SE model of acquired epilepsy. Methods: Juvenile male Sprague-Dawley rats (150-200g) underwent 1h of SE by intraperitoneal kainate (16mg/kg, i.p.). At 2 and 4wks following SE, animals were sedated using ketamine/xylazine/acepromazine i.p. and single channel EKG recordings were obtained. Heart rate (HR), PR, QRS and QTc intervals were manually calculated. Descriptive statistics and Student t-test were performed for each variable. Two-way ANOVA was performed to evaluate HR, PR, QRS and QTc changes over time in the sham and the SE groups. Values were expressed as mean±SEM. Results: At 2wks following SE, compared with the age-matched sham animals, the SE group exhibited elevated HR (281±6 vs. 311±10 bpm, sham vs. SE, n=10-14/group, p<0.05), increased QRS (59±4 vs. 80±5 msec, sham vs. SE, n=10-14/group, p<0.01) and QTc (244±12 vs. 307±12 msec, sham vs. SE, n=10-14/group, p<0.01). At 4wks following SE, both sham and SE animals exhibited age-related decreases in HR. Additionally, the SE animals exhibited some normalization of QRS and QTc intervals. However, compared with the sham animals, the SE group still exhibited higher HR (259±4 vs. 279±3 bpm, sham vs. SE, n=10-13/group, p<0.001), longer QRS (53±4 vs. 69±5 msec, sham vs. SE, n=10-13/group, p<0.05) and QTc (234±7 vs. 297±28 msec, sham vs. SE, n=10-13/group, p<0.01). Conclusions: Our findings suggest that SE induces early cardiac changes. These alterations persist in the early epileptogenesis; raising the possibility that cardiac remodeling may occur concurrently with the development of epilepsy in this model. Studies are ongoing to examine whether the appearance of recurrent seizures later in life will exaggerate the cardiac phenotype in the epileptic animals.