Cardiac consequences of epileptic seizures in the tetanus neurotoxin model of temporal lobe epilepsy

Thesis

Death is the most destructive outcome of epilepsy. Around 18% of deaths in those with epilepsy cannot be attributed to the disease itself; these deaths are collectively categorised as Sudden Unexplained Deaths in Epilepsy (SUDEP). Currently, the cause of SUDEP is hypothesised to involve seizure-induced respiratory or cardiac failure. Ictal (during seizure) central and obstructive apnoea, decreases in ictal oxygen saturation, changes in blood pressure, heart rate, autonomic control and cardiac conductivity in both patients and animal models have all been observed. In order to explore the effects of seizures on the autonomic control and cardiac conductivity, tetanus neurotoxin was injected into the ventral hippocampus of male Wistar rats; previously implanted with biopotential radiotelemeters.

Continuous recordings of electrocardiogram, electrocorticogram, and video were made for six to eight weeks post induction of epilepsy. The conductivity of the heart was analysed by calculating the PR, QT, corrected QT (QTc) intervals and QRS width. The central control of the heart was explored by analysing the interictal heart rate and calculating various time-based Heart rate variability measures. Statistical analysis was performed using One-Way ANOVA with Bonferroni post-hoc comparisons.

Increases in the PR interval, QRS width, RR interval, QT and QTc intervals were observed between preinduction and 150th seizure. The change in PR interval, RR interval, and QT interval persisted into the Post Seizure State. Significant differences were not observed for any of the Heart Rate Variability measures. The increase in QT and QTc intervals indicate a pathological change in the time taken for cardiac ventricular depolarisation and repolarisation to occur. The changes in PR and RR intervals and QRS width are not physiologically significant. Due to large variation between animals, meaningful conclusions about changes in central control of the heart could not be drawn. This study ultimately shows that the tetanus neurotoxin model of temporal lobe epilepsy induces changes in cardiac conductivity, and could aid in investigating the mechanisms through which SUDEP occurs.

Authors: Ashby-Lumsden, A

• Type of award: MSc by Research
• Level of award: Masters
• Awarding institution: University of Oxford
• Language: English