[Skip to Content]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address Please contact the publisher to request reinstatement.
[Skip to Content Landing]
Young  T.  Analytic epidemiology studies of sleep disordered breathing—what explains the gender difference in sleep disordered breathing?  Sleep. 1993;16(8)(suppl):S1-S2.PubMedGoogle Scholar
Lévy  P, Bonsignore  MR, Eckel  J.  Sleep, sleep-disordered breathing and metabolic consequences.  Eur Respir J. 2009;34(1):243-260.PubMedGoogle ScholarCrossref
Somers  VK, White  DP, Amin  R,  et al.  Sleep apnea and cardiovascular disease: an American Heart Association/American College of Cardiology Foundation Scientific Statement from the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, Stroke Council, and Council on Cardiovascular Nursing.  J Am Coll Cardiol. 2008;52(8):686-717.PubMedGoogle ScholarCrossref
Engleman  HM, Douglas  NJ.  Sleep · 4: Sleepiness, cognitive function, and quality of life in obstructive sleep apnoea/hypopnoea syndrome.  Thorax. 2004;59(7):618-622.PubMedGoogle ScholarCrossref
Hendricks  JC, Kline  LR, Kovalski  RJ, O’Brien  JA, Morrison  AR, Pack  AI.  The English bulldog: a natural model of sleep-disordered breathing.  J Appl Physiol. 1987;63(4):1344-1350.PubMedGoogle Scholar
Kimoff  RJ, Makino  H, Horner  RL,  et al.  Canine model of obstructive sleep apnea: model description and preliminary application.  J Appl Physiol. 1994;76(4):1810-1817.PubMedGoogle Scholar
Philip  P, Gross  CE, Taillard  J, Bioulac  B, Guilleminault  C.  An animal model of a spontaneously reversible obstructive sleep apnea syndrome in the monkey.  Neurobiol Dis. 2005;20(2):428-431.PubMedGoogle ScholarCrossref
Farré  R, Nácher  M, Serrano-Mollar  A,  et al.  Rat model of chronic recurrent airway obstructions to study the sleep apnea syndrome.  Sleep. 2007;30(7):930-933.PubMedGoogle Scholar
Dematteis  M, Godin-Ribuot  D, Arnaud  C,  et al.  Cardiovascular consequences of sleep-disordered breathing: contribution of animal models to understanding the human disease.  ILAR J. 2009;50(3):262-281.PubMedGoogle ScholarCrossref
Brooks  D, Horner  RL, Floras  JS, Kozar  LF, Render-Teixeira  CL, Phillipson  EA.  Baroreflex control of heart rate in a canine model of obstructive sleep apnea.  Am J Respir Crit Care Med. 1999;159(4, pt 1):1293-1297.PubMedGoogle ScholarCrossref
Cartee  TV, Monheit  GD.  An overview of botulinum toxins: past, present, and future.  Clin Plast Surg. 2011;38(3):409-426.PubMedGoogle ScholarCrossref
Johnson-Delaney  CA, Orosz  SE.  Rabbit respiratory system: clinical anatomy, physiology and disease.  Vet Clin North Am Exot Anim Pract. 2011;14(2):257-266.PubMedGoogle ScholarCrossref
Bellemare  F, Pecchiari  M, Bandini  M, Sawan  M, D’Angelo  E.  Reversibility of airflow obstruction by hypoglossus nerve stimulation in anesthetized rabbits.  Am J Respir Crit Care Med. 2005;172(5):606-612.PubMedGoogle ScholarCrossref
Oliven  A, Odeh  M, Geitini  L,  et al.  Effect of coactivation of tongue protrusor and retractor muscles on pharyngeal lumen and airflow in sleep apnea patients.  J Appl Physiol. 2007;103(5):1662-1668.PubMedGoogle ScholarCrossref
Kairaitis  K, Stavrinou  R, Parikh  R, Wheatley  JR, Amis  TC.  Mandibular advancement decreases pressures in the tissues surrounding the upper airway in rabbits.  J Appl Physiol. 2006;100(1):349-356.PubMedGoogle ScholarCrossref
Schwartz  AR, Patil  SP, Laffan  AM, Polotsky  V, Schneider  H, Smith  PL.  Obesity and obstructive sleep apnea: pathogenic mechanisms and therapeutic approaches.  Proc Am Thorac Soc. 2008;5(2):185-192.PubMedGoogle ScholarCrossref
O’Donnell  CP, King  ED, Schwartz  AR, Robotham  JL, Smith  PL.  Relationship between blood pressure and airway obstruction during sleep in the dog.  J Appl Physiol. 1994;77(4):1819-1828.PubMedGoogle Scholar
Guilleminault  C.  Benzodiazepines, breathing, and sleep.  Am J Med. 1990;88(3A):25S-28S.PubMedGoogle ScholarCrossref
Neuzeret  PC, Gormand  F, Reix  P,  et al.  A new animal model of obstructive sleep apnea responding to continuous positive airway pressure.  Sleep. 2011;34(4):541-548.PubMedGoogle Scholar
Scherschlicht  R, Marias  J.  Effects of oral and intravenous midazolam, triazolam and flunitrazepam on the sleep-wakefulness cycle of rabbits.  Br J Clin Pharmacol. 1983;16(suppl 1):29S-35S.PubMedGoogle ScholarCrossref
Pivik  RT, Bylsma  FW, Cooper  P.  Sleep-wakefulness rhythms in the rabbit.  Behav Neural Biol. 1986;45(3):275-286.PubMedGoogle ScholarCrossref
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

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.