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Original Investigation
August 2013

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

Author Affiliations
  • 1Department of Otorhinolaryngology, Korea Cancer Center Hospital, Seoul, South Korea
  • 2Seoul National University College of Medicine, Seoul, South Korea
  • 3Department of Otorhinolaryngology, Busan National University College of Medicine, Busan, South Korea
  • 4Department of Otorhinolaryngology, Kyungsang National University College of Medicine, Jinju, South Korea
  • 5Department of Otorhinolaryngology, Seoul National University Bundang Hospital, Seongnam, South Korea
  • 6Department of Rehabilitation Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
  • 7Department of Psychiatry, Seoul National University Bundang Hospital, Seongnam, South Korea
JAMA Otolaryngol Head Neck Surg. 2013;139(8):834-840. doi:10.1001/jamaoto.2013.4001
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.

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