Abstracts

Rationale: We investigated ictal apnoeas in an acute rat seizure model, expanding findings on ictal apnoea mechanism gained using a rat model of temporal lobe epilepsy, previously reported at AES 2023. The relationship between seizures and respiratory dysfunctions could shed light on the mechanisms involved in SUDEP.

Methods: Six adult Wistar rats of both sexes were implanted with intranasal thermocouple, electrodes in dorsal hippocampus and contralateral neocortex, and EMG leads intra-abdominally (for diaphragm) and subcutaneously (dorsal rostrolumbar) during aseptic surgery. All sensors connected to a socket cemented to the skull. After recovery from surgery, video-EEG recordings were made through a bespoke preamplifier (Digitimer Ltd), wires and counterbalanced slip rings, and digitized by a CED1401 running SPIKE2 (CED Ltd). Each rat received injection of pentylenetetrazole (PTZ, 75 mg/kg i.p.).

Results: PTZ injection initiated seizures after 39-220 s, lasted 55.3±32.4 s and recurred until death after 40-150 min. Mean apnoea duration was 9.3±13.6 s. Diaphragm EMG during apnoeas was mostly atonic (27 of 35 apnoeas), consistent with the loss of central respiratory drive. The remaining 8 apnoeas had an additional initial tonic EMG component (8.5±15.0 s). All apnoeas that initiated with a tonic signal progressed into an atonic EMG. In all but one rat, terminal apnoeas are caused by atonic diaphragms. One case shows evidence of transient obstructive apnoeas lasting 23 s, 128 s before the terminal apnoea. Median tonic diaphragm EMG_RMS is 35.2±5.7 µV, inspiratory peak EMG_RMS is 15.1±20.4 µV, and expiratory trough is 3.7±1.5 µV. Apnoeas during the tonic phase appear to have EMG_RMS greater than during eupnoeic respiration; those during the atonic phase appear at the lower end of eupnoeic EMG_RMS. We analyse EMGs: tonic-diaphragm apnoeas EMGs differ from the expiratory EMG minima (Wilcoxon Signed Rank test P=0.012) but do not differ significantly from inspiratory maxima (P=0.161); atonic-diaphragm-EMG apnoeas differ from both maxima and minima of eupnoeic EMGs (P< 0.001). Atonic apnoea EMGs overlap expiration more than inspiration. The median absolute difference of apnoea EMG from expiration is 1.07±2.4 µV, significantly less than the absolute difference from inspiration of 9.4±5.2 µV) (Related-Samples Wilcoxon Signed-Rank Test P< 0.001).