Seizures induce obstructive apnea in DBA/2J audiogenic seizure-prone mice: Lifesaving impact of tracheal implants.
SUDEP
apnea
respiratory arrest
sudden death
Journal
Epilepsia
ISSN: 1528-1167
Titre abrégé: Epilepsia
Pays: United States
ID NLM: 2983306R
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
11
11
2019
revised:
29
12
2019
accepted:
30
12
2019
pubmed:
17
1
2020
medline:
11
7
2020
entrez:
17
1
2020
Statut:
ppublish
Résumé
The mechanism(s) for sudden death in epilepsy (SUDEP) remain(s) unknown, but seizure spread to brainstem areas serving autonomic and respiratory function is critical. In a rat model, we established a mechanism for SUDEP that involves seizure-induced laryngospasm and obstructive apnea lasting until respiratory arrest. We hypothesized that DBA/2J mice, which display lethal audiogenic seizures, would be protected from death by implanting a tracheal T-tube as a surrogate airway. In a 2 × 2 design, mice were implanted with either open or closed tracheal T-tubes and treated with either low-dose ketamine/xylazine to moderate thoracic spasm during the tonic seizure phase or no drug. Animals receiving both treatments had the highest survival rate, followed by animals receiving the open tube without ketamine/xylazine. The odds ratio for survival was >20 higher with an open T-tube (odds ratio = 24.14). The impact of open tracheal tubes indicates that the mechanism of death in DBA/2J mice involves seizure-induced upper airway obstruction until respiratory arrest. These results, our rat work, and our demonstration of inspiratory effort-based electromyographic signals and electrocardiographic abnormalities in rats and humans suggest that seizure-induced laryngospasm and obstructive apnea directly link seizure activity to respiratory arrest in these sudden death examples.
Identifiants
pubmed: 31944280
doi: 10.1111/epi.16431
pmc: PMC7033013
mid: NIHMS1066048
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13-e16Subventions
Organisme : NINDS NIH HHS
ID : R03 NS104796
Pays : United States
Informations de copyright
Wiley Periodicals, Inc. © 2020 International League Against Epilepsy.
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