Cardiac effects of repeated focal seizures in rats induced by intrahippocampal tetanus toxin:bradyarrhythmias, tachycardias and prolonged interictal QT interval

Objective To determine electrical changes in the heart in a chronic, nonstatus model of epilepsy. Methods Electrocorticography (ECoG) and electrocardiography (ECG) of nine animals (five made epileptic by intrahippocampal injection of tetanus neurotoxin (TeNT) and four controls), are monitored continuously by radiotelemetry for up to 7 weeks. Results Epileptic animals develop a median of 168 seizures, with postictal tachycardias reaching a mean of 487 beats/min and lasting a mean of 661 seconds. Ictal changes in heart rate include tachycardia and in the case of convulsive seizures, bradyarrhythmias resembling Mobitz type 1 second‐degree atrioventricular block; notably the P‐R interval increased before block. Postictally, the amplitude of T wave increases. Interictally, QT dependence on RR is modest and conventional QT corrections prove ineffective. Interictal QT intervals, measured at a heart rate of 400 bpm, increased from 65 to 75 ms, an increase dependent on seizure incidence over the preceding 10‐14 days. Significance Repeated seizures induce a sustained tachycardia and increase in QT interval of the ECG and evoke arrhythmias including periods of atrioventricular block during Racine type 4 and 5 seizures. These changes in cardiac function may predispose to development in fatal arrhythmias and sudden death in humans with epilepsy.</p

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

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.</p

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

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.</p

Ictal bradycardia and tachycardia observed in the tetanus toxin model of temporal lobe epilepsy in the freely moving rat

Those with epilepsy have a higher risk of sudden death than the general population; however, the mechanism of these sudden deaths is unknown. Fatal arrhythmia generation during seizure, along with changes in autonomic tone, are hypothesised to be important factors. Six Wistar rats were stereotaxically injected with tetanus toxin into the ventral hippocampus, and implanted with radiotelemeters to record electrocardiogram and electroencephalogram. The heart rate was analysed in pre-ictal, ictal and post-ictal epochs with the aim of demonstrating the changes in autonomic tone during seizure. Ictal bradycardia was observed in 89% of the seizures analysed, with post-ictal tachycardia in 93%. Further, potentially lethal arrhythmias were observed during seizure. Missed beats (59%), ventricular premature depolarisation (22%) and ventricular fibrillation (17%) are risk factors for sudden death in the general population and their presence during seizure could potentially be fatal. Whilst this study has demonstrated changes in autonomic tone and cardioarrhythmia generation; the extent of the changes and their mechanism need to be explored further. Nevertheless, this research validates the tetanus toxin model of temporal lobe epilepsy as a tool for investigating sudden death in epilepsy