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Original Investigation |

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

Myung-Chul Lee, MD1; Chul Hee Lee, MD2; Sung-Lyong Hong, MD3; Sang-Wook Kim, MD4; Woo-Hyun Lee, MD5; Jae Young Lim, MD2,6; Sam Joe, BD5; In-Young Yoon, MD2,7; Jeong-Whun Kim, MD, PhD2,5
[+] 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.
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Published online

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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Figures

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Figure 1.
Sleep Staging

Real-time monitoring was performed for sleep staging with a portable polysomnography device (Embletta X100; Embla Systems) in rabbits.

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Figure 2.
Induction of Genioglossus Paralysis

After the rabbit was anesthetized, botulinum toxin type A was injected transorally.

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Figure 3.
Acquisition of Respiratory Events

During drug-induced sleep, sleep apneas, and hypopneas were scored using a nasal pressure sensor and pulse oximetry of the sleep-screening tool ApneaLink (ResMed).

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Figure 4.
Polysomnographic Finding

The 30-second epoch obtained by Embletta X100 (Embla Systems) shows electrooculography (EOG), electroencephalography (EEG), chin electromyography (EMG), nasal air flow, nasal air pressure, and breathing efforts. Sleep spindles are identified on the EEG (arrows).

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Figure 5.
Respiratory Events During Drug-Induced Sleep

Apneas (red bands with “A”) and hypopneas (light blue bands with “H”) were detected using ApneaLink (ResMed). Before botulinum toxin was injected, neither apneas nor hypopneas were induced (A). In contrast, after injection of botulinum toxin, apneas and hypopneas developed. These events are shown in 3-minute epochs (B and C).

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Figure 6.
Evaluation of Genioglossus Activity

The amplitude and area of the compound muscle action potential were higher before botulinum toxin injection (A) than after injection (B). Before injection, the electromyographic activity of the genioglossus was normal in configuration of motor unit action potential (C). However, the insertional activity remarkably decreased, and motor unit action potentials were sparsely detected after injection (D).

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