Rationale: We investigate the presence of cardiac abnormalities in a rat model of temporal lobe epilepsy.
While respiratory dysfunction has dominated recent work on SUDEP, cardiac pathophysiologies do occur and may increase risk of SUDEP and other adverse outcomes.
Methods: Eleven adult male Wistar rats receive unilateral injections of tetanus toxin into ventral hippocampus. In the same aseptic surgery under general anaesthesia, we implant: an intranasal thermocouple, LFP electrodes in the dorsal ipsilateral hippocampus and/or contralateral ECoG electrodes, and subcutaneous ECG leads in a lead II configuration. All sensors are connected to a socket cemented into the skull. After the rats recover from the surgery, continuous video telemetry is acquired from a custom-built preamplifier (Digitimer Ltd. UK), umbilical wires and counterbalanced slip rings. This signal is digitized by a CED1401 signal acquisition system running SPIKE2 (CED Ltd, UK).
Results: As we previously report, we observe bradyarrhythmias during spontaneous seizures
1. In this new experiment we also compare the relationship between cardiac and respiratory pathologies during ictal events. Out of 613 convulsive seizures analysed, 315 are associated with apnoeas and bradycardia. Where both signals are available, apnoeas are always associated with significant slowing down of the heart rate.
The difference between the last R-wave before bradycardia and onset of hypopnoea is 2.3s ±8.8 (SD). During ictal events we observe premature ventricular contractions (PVC). In 40 random seizures analysed from 5 rats, 30 seizures are associated with PVCs, (median per seizure = 2, 3
rd quartile = 4, maximum = 18). PVCs occur both during ictal apnoeas (14/30), and during seizures without apnoeas (16/30). Seizures with the most PVCs (± 15) have their ectopic beats interspersed between sinus rhythm beats suggesting a ventricular arrhythmia (See Figure). This is in stark contrast to our control animals where no such events occur. These events were not observed interictally suggesting that the source of the pathology is ictally mediated.
Conclusions: We observe cardiac and respiratory pathologies in a chronic animal model of temporal lobe epilepsy. Every respiratory apnoea was coupled with a significant slowing of the heart rate. These events were closely linked temporally, suggesting a unified mechanism. The ictal PVCs we report here provide an additional cardiac dysfunction with potential clinical significance, possibly exacerbating the effect of respiratory dysfunction, increasing the risk of
SUDEP 1. Jefferys JGR, Ashby-Lumsden A, Lovick TA. Cardiac effects of repeated focal seizures in rats induced by intrahippocampal tetanus toxin: Bradyarrhythmias, tachycardias, and prolonged interictal QT interval. Epilepsia. 2020;61:798-809.
Funding: Czech Health Research Council, Ministry of Health of the Czech Republic grant NU21-04-00601