Establishment of a Rabbit Model of Obstructive Sleep Apnea by Paralyzing the Genioglossus

Abstract

IMPORTANCE This study presents an innovative method for developing a neuromuscular model of obstructive sleep apnea (OSA). OBJECTIVE To establish a new OSA animal model simulating real upper airway conditions during sleep. DESIGN AND SETTING In vivo animal study at an academic tertiary referral center. SUBJECTS A total of 27 New Zealand white male rabbits were used. INTERVENTION Sleep was induced by intramuscular injection of 0.3 mL/kg of tiletamine hydrochloride plus zolazepam hydrochloride and 0.2 mL/kg of xylazine. Upper airway obstruction was induced by injecting botulinum toxin type A (2.5 U in 8 rabbits, 5.0 U in 10 rabbits, and 7.5 U in 1 rabbit) into the genioglossus. Eight rabbits were injected with normal saline as a control. MAIN OUTCOMES AND MEASURES Drug-induced sleep was evaluated using a portable polysomnography device for electroencephalography, electrooculography, chin electromyography, nasal airflow, breathing efforts, and pulse oxymetry. Respiratory events (apneas or hypopneas) during sleep were evaluated using a sleep-screening tool. RESULTS All the rabbits showed no apneas or hypopneas before injection of botulinum toxin type A. In the control rabbits injected with normal saline, apneas or hypopneas were not found. The respiratory events were observed in 5 of 8 rabbits injected with 2.5 U of botulinum toxin type A, whereas they were observed in 7 of 10 rabbits injected with 5.0 U of botulinum toxin type A. The median (interquartile range) apnea hypopnea index was 9.6 (5.3-14.8) per hour and 45.6 (21.5-70.5) per hour in the rabbits injected with 2.5 U and 5.0 U of botulinum toxin type A, respectively (P = .03). CONCLUSIONS AND RELEVANCE An animal model of OSA could be developed by paralyzing the genioglossus in rabbits. This model may contribute to identifying the pathogenesis of upper airway obstruction in OSA and to developing new diagnostic or treatment devices targeting specific obstruction sites.