Diving responses elicited by nasopharyngeal irrigation mimic seizure-associated central apneic episodes in a rat model

Abstract

The spread of epileptic seizure activity to brainstem respiratory and autonomic regions can elicit episodes of obstructive apnea and of central apnea with significant oxygen desaturation and bradycardia. Previously, we argued that central apneic events were not consequences of respiratory or autonomic activity failure, but rather an active brainstem behavior equivalent to the diving response resulting from seizure spread. To test the similarities of spontaneous seizure-associated central apneic episodes to evoked diving responses, we used nasopharyngeal irrigation with either cold water or mist for 10 or 60 s to elicit the diving response in urethane-anesthetized animals with or without kainic acid-induced seizure activity. Diving responses included larger cardiovascular changes during mist stimuli than during water stimuli. Apneic responses lasted longer than 10 s in response to 10 s stimuli or about 40 s in response to 60 s stimuli, and outlasted bradycardia. Repeated 10 s mist applications led to an uncoupling of the apneic episodes (which always occurred) from the bradycardia (which became less pronounced with repetition). These uncoupled events matched the features of observed spontaneous seizure-associated central apneic episodes. The duration of spontaneous central apneic episodes correlated with their frequency, i.e. longer events occurred when there were more events. Based on our ability to replicate the properties of seizure-associated central apneic events with evoked diving responses during seizure activity, we conclude that seizure-associated central apnea and the diving response share a common neural basis and may reflect an attempt by brainstem networks to protect core physiology during seizure activity.

Keywords: Apnea; Autonomic; Cardiovascular; Diving reflex; Epilepsy; Respiratory.