High-risk KO mice had more orexin neurons in the lateral hypothalamus. Intermittent bradycardia was more prevalent in high-risk KO mice, an effect that may be the result of increased parasympathetic drive. The number of orexin neurons in the lateral hypothalamus was determined with immunohistochemistry. The role of orexin was determined within subject following acute treatment with a dual orexin receptor antagonist (DORA, 100 mg/kg). Respiration was determined with noninvasive airway mechanics technology. Heart rate and SaO 2 were determined noninvasively with ECGenie and pulse oximetry. Here, we determined (a) heart rate, respiratory rate, and blood oxygen saturation (SaO 2 ) in low-risk and high-risk knockout (KO) mice and (b) whether blocking receptors for orexin, a cardiorespiratory neuromodulator, influences cardiorespiratory function mice or longevity in high-risk KO mice. Whether a progressive pathophysiology develops and increases risk of SUDEP remains unknown. Immediately preceding sudden unexpected death in epilepsy (SUDEP), patients experienced a final generalized tonic-clonic seizure (GTCS), rapid ventilation, apnea, bradycardia, terminal apnea, and asystole.
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