Relation of autonomic and cardiac abnormalities to ventricular fibrillation in a rat model of epilepsy

Cardiac autonomic, conduction, and structural changes may occur in epilepsy and may contribute to sudden unexpected death in epilepsy (SUDEP), e.g. by increasing the risk for ventricular fibrillation (VF). In a model of chronic seizures in rats, we sought to study (1) cardiac and autonomic derangements that accompany the epileptic state, (2) whether chronically seizing rats experienced more significant cardiac effects after severe acute seizures, and (3) the susceptibility of chronically seizing rats to VF arising from autonomic and hypoxemic changes, which commonly occur during seizures. Sprague-Dawely rats were injected with saline or kainic acid to induce chronic seizures. At 2-3 months or 7-11 months after injection, these rats were studied with both 12-lead electrocardiography (to assess heart rate variability and QT dispersion) and echocardiography under ketamine/xylazine or urethane anesthesia. Hearts were subsequently excised, weighed, and examined histologically. Epileptic rats exhibited decreased vagal tone, increased QT dispersion, and eccentric cardiac hypertrophy without significant cardiac fibrosis, especially at 7-11 months post-injection. Of these three findings, vagal tone was inversely correlated with heart weights. Epileptic rats exhibited diminished systolic function compared to controls after severe acute seizures. However, animals with long-standing chronic seizures were less susceptible to autonomic/hypoxemia-driven VF, and their susceptibility inversely correlated with mean left ventricular wall thickness on histology. On the basis of this model, we conclude that cardiac changes accompany epilepsy and these can lead to significant seizure-associated cardiac performance decreases, but these cardiac changes actually lower the probability of VF.