Abstracts

Rationale: The main theories for mechanisms of SUDEP are dysfunction of the respiratory and/or cardiac systems. We used a chronic model of temporal lobe epilepsy in rats to monitor respiration, ECG and cortical activity by radiotelemetry in freely moving rats. The aim was to identify changes in heart rate and respiration during and following spontaneous seizures. Methods: Under isoflurane anaesthesia electrodes were implanted on the chest wall to record ECG (leads 1 and in some cases also lead 2), respiratory rate was monitored by measuring changes in air temperature using a thermocouple implanted into the nasal passage, and ECoG was recorded by electrodes positioned in bur holes over the hippocampal region. Leads from all devices were tunnelled to a subcutaneous "Bionode" radiotelemetry device developed in-house. During the same surgery 20 ng tetanus neurotoxin (TeNT) in 800 nl buffered saline was injected into the hippocampus under stereotaxic guidance. After recovery, recordings were made for at least 4 weeks. Results: Rats in this experiment started seizing 14 - 21 days after injection. We focussed on seizures with secondary generalisation with repeated rearing and falling. Currently we have analysed 8 seizures (2 or 3 from each of 3 rats). As reported previously seizures were characterised by irregularities in heart rate (tachycardia up t0 340 min-1 and bradycardia down to 125 min-1, as well as arrhythmias). There was prolonged postictal tachycardia, from a preictal baseline of 318 min-1 to 427 min-1 (means of 8 seizures), with widely dispersed durations from 6 min up to 30 min.Respiratory rate accelerated during seizures, from a preictal mean of 50 min-1 to 108 min-1, with a marked reduction in amplitude of the temperature fluctuations. Respiration then became irregular, with ictal apnoeas in 2 of 8 rats, lasting 20 and 30 s. Postictal respiration accelerated to a mean of 144 min-1. The amplitude of the temperature fluctuations varied considerably postictally, consistently smaller than preictal respiration in on rat, and consistently bigger in the other two. Postictal respiratory changes lasted a minimum of 2 min and up to 17 min. Conclusions: Secondarily generalised seizures in the rat TeNT model of temporal lobe epilepsy are associated with disrupted respiration and cardiac function. Funding: Supported by Epilepsy Research UK, NSF and DARPA