Sudden unexplained death in epilepsy (SUDEP), where the death of a patient cannot be attributed to any other cause, is a relatively poorly understood phenomenon. Sudden death is over 20 times more prevalent in people with epilepsy than in the general population and is of considerable concern to those at risk and their families. The mechanism of SUDEP is unknown, but ictal respiratory depression, autonomic dysfunction and fatal arrhythmia are all hypothesised to have a role. Using the Tetanus Neuro-Toxin (TeNT) model of temporal lobe epilepsy, we examined the affect of chronic epileptic seizures on the electrocardiogram (ECG) of freely moving rats.Adult male Wistar rats were injected with 2.5ng TeNT in 1μl phosphate buffered saline with bovine serum albumin at 200nl.min-1 (toxin omitted in controls) into the ventral hippocampus. Electrocorticogram and ECG were continuously recorded via dual-biopotential Telemetry Research radiotelemeters (Millar Instruments, US) implanted ~2 weeks before injection. Both surgeries were performed under isoflurane anaesthesia (5% induction, 2-3% maintenance). Animals were housed with naïve companion rats and video-recorded for seizure classification. Seizure-related changes in heart rate and the incidence of arrhythmias were analysed. Data are given as mean±SEM. Seizures lasted 75.3±2.9 s. They induced dramatic changes in heart rate: ictal bradycardia occurred in 89% of seizures with the heart rate as low as 70 bpm, along with ictal tachycardia (447.5±4.7 bpm) that persisted 863.5±86.7s post-ictally. Seizure-induced arrhythmias occurred in 71% of seizures, with missed beats (59%), ventricular premature depolarisations (22%) and ventricular fibrillation (17%) seen both in isolation and in concert. The ECG waveform also changed, with the P-wave absent for many heartbeats in the majority of seizures. Our results demonstrate that repeated brief epileptic seizures have substantial effects on heart rate, with arrhythmias present during the majority of seizures. Similar cardiac consequences of seizures have been seen in human patients. We conclude that the TeNT model provides a valuable tool to investigate autonomic mechanisms implicated in SUDEP.
Physiology 2014 (London, UK) (2014) Proc Physiol Soc 31, PCA048
Poster Communications: Cardiac effects of brief seizures in a chronic model of temporal lobe epilepsy
A. Ashby-Lumsden1, W. Chang1, T. Lovick2, J. Jefferys1
1. School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, United Kingdom. 2. School of Physiology and Pharmacology, University of Bristol, Bristol, United Kingdom.
View other abstracts by:
Where applicable, experiments conform with Society ethical requirements.