Laryngospasm, central and obstructive apnea during seizures: Defining pathophysiology for sudden death in a rat model.
Seizure spread into the autonomic nervous system can result in life-threatening cardiovascular and respiratory dysfunction. Here we report on a less-studied consequence of such autonomic derangements-the possibility of laryngospasm and upper-airway occlusion. We used parenteral kainic acid to induce recurring seizures in urethane-anesthetized Sprague Dawley rats. EEG recordings and combinations of cardiopulmonary monitoring, including video laryngoscopy, were performed during multi-unit recordings of recurrent laryngeal nerve (RLN) activity or head-out plethysmography with or without endotracheal intubation. Controlled occlusions of a tracheal tube were used to study the kinetics of cardiac and respiratory changes after sudden obstruction. Seizure activity caused significant firing increases in the RLN that were associated with abnormal, high-frequency movements of the vocal folds. Partial airway obstruction from laryngospasm was evident in plethysmograms and was prevented by intubation. Complete glottic closure (confirmed by laryngoscopy) occurred in a subset of non-intubated animals in association with the largest increases in RLN activity, and cessation of airflow was followed in all obstructed animals within tens of seconds by ST-segment elevation, bradycardia, and death. Periods of central apnea occurred in both intubated and non-intubated rats during seizures for periods up to 33s and were associated with modestly increased RLN activity, minimal cardiac derangements, and an open airway on laryngoscopy. In controlled complete airway occlusions, respiratory effort to inspire progressively increased, then ceased, usually in less than 1min. Respiratory arrest was associated with left ventricular dilatation and eventual asystole, an elevation of systemic blood pressure, and complete glottic closure. Severe laryngospasm contributed to the seizure- and hypoxemia-induced conditions that resulted in sudden death in our rat model, and we suggest that this mechanism could contribute to sudden death in epilepsy.
Department of Physiology & Pharmacology, State University of New York, Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, New York, 11203, United States.
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Nakase
Department of Cell Biology, State University of New York, Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, New York, 11203, United States; Department of Otolaryngology, State University of New York, Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, New York, 11203, United States.
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Kollmar
Department of Medicine (Division of Cardiology), State University of New York, Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, New York, 11203, United States.
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Lazar
Department of Otolaryngology, State University of New York, Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, New York, 11203, United States.
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Arjomandi
Department of Otolaryngology, State University of New York, Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, New York, 11203, United States.
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Sundaram
Department of Otolaryngology, State University of New York, Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, New York, 11203, United States.
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Silverman
Department of Physiology & Pharmacology, State University of New York, Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, New York, 11203, United States.
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Orman
Department of Statistical Design & Analysis, State University of New York, Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, New York, 11203, United States.
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Weedon
Department of Statistical Design & Analysis, State University of New York, Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, New York, 11203, United States.
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Stefanov
Department of Cell Biology, State University of New York, Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, New York, 11203, United States; Department of Otolaryngology, State University of New York, Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, New York, 11203, United States.
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Savoca
Department of Physiology & Pharmacology, State University of New York, Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, New York, 11203, United States.
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Tordjman
Department of Cell Biology, State University of New York, Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, New York, 11203, United States.
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Stiles
Department of Medicine (Division of Cardiology), State University of New York, Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, New York, 11203, United States.
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Ihsan
Department of Medicine (Division of Cardiology), State University of New York, Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, New York, 11203, United States.
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Nunez
Research Initiative for Scientific Enhancement (RISE) Program, City University of New York, Medgar Evers College, 1638 Bedford Avenue, Brooklyn, New York, 11225, United States.
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Guzman
Department of Physiology & Pharmacology, State University of New York, Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, New York, 11203, United States; Department of Neurology, State University of New York, Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, New York, 11203, United States. Electronic address: mark.stewart@downstate.edu.
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Stewart
D000818:Animals; D001921:Brain / Q000503:physiopathology; D003645:Death, Sudden; D004195:Disease Models, Animal; D006323:Heart Arrest / Q000209:etiology / Q000503:physiopathology; D000860:Hypoxia / Q000209:etiology / Q000503:physiopathology; D007511:Ischemia / Q000209:etiology / Q000503:physiopathology; D007608:Kainic Acid; D007823:Laryngeal Nerves / Q000503:physiopathology; D007826:Laryngismus / Q000150:complications / Q000503:physiopathology*; D008297:Male; D009068:Movement / Q000502:physiology; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000150:complications / Q000503:physiopathology*; D020182:Sleep Apnea, Central / Q000150:complications / Q000503:physiopathology*; D020181:Sleep Apnea, Obstructive / Q000150:complications / Q000503:physiopathology*; D014827:Vocal Cords / Q000503:physiopathology
D007608:Kainic Acid
Arrhythmia; Asphyxiation; Cardiopulmonary arrest; Larynx; SUDEP