title: Inner ear insult ablates the arousal response to hypoxia and hypercarbia.
abstract: BACKGROUND
  Sudden Infant Death Syndrome (SIDS) remains the leading cause of infant mortality in Western societies. A prior study identified an association between hearing suppression on the newborn hearing test and subsequent death from SIDS. This is the first finding of an abnormality in SIDS cases prior to death. A following study identified that inner ear dysfunction precipitates a marked suppression of the hypercapnic ventilatory response (HCVR). Failure of arousal has been proposed to be a key component in SIDS. The objective of the present study was to assess whether inner ear dysfunction not only weakens the hypercapnic response, but also plays a role in suppressing the arousal response to suffocating gas mixtures.
  
  
  METHODS
  Wild-type mice (n=28) received intra-tympanic gentamicin (IT-Gent) injections bilaterally or unilaterally to precipitate inner ear hair cell dysfunction. Three control groups (n=22) received intra-tympanic saline (IT-Saline) bilaterally or unilaterally (right or left), or intra-peritoneal gentamicin (IP-Gent). The body movement arousal responses to severe hypoxia-hypercarbia combined (5% CO2 in nitrogen) were tested under light anesthesia 8 days following the administration of gentamicin or saline.
  
  
  RESULTS
  After injections, the bilateral and unilateral IT-Gent-treated animals behaved similarly to controls, however the HCVR as well as the arousal movements in response to severe hypoxia-hypercarbia were suppressed in IT-Gent-treated animals compared to control animals (P<0.05). Thus the HCVR was significantly decreased in the bilateral (n=9) and unilateral IT-Gent-treated mice (n=19) compared to bilateral (n=7) and unilateral IT-Saline (n=9) control groups (p<0.05). Arousal movements were suppressed in the bilateral IT-Gent group (n=9) compared to bilateral IT-Saline controls (n=7, P<0.0001) and in the unilateral IT-Gent group (n=19) compared to unilateral IT-Saline controls (n=10, P<0.0001).
  
  
  CONCLUSIONS
  The findings support the theory that inner ear dysfunction could be relevant in the pathophysiology of SIDS. The inner ear appears to play a key role in arousal from suffocating gas mixtures that has not been previously identified.
authors.affiliation: Department of Anesthesia, Seattle Children's Hospital, 4800 Sandpoint Way NE, Seattle, WA 98115, United States. Electronic address: travis.allen@seattlechildrens.org.
authors.forename: T
authors.initials: T
authors.lastname: Allen
authors.forename: A J
authors.initials: AJ
authors.lastname: Garcia Iii
authors.forename: J
authors.initials: J
authors.lastname: Tang
authors.forename: J M
authors.initials: JM
authors.lastname: Ramirez
authors.forename: D D
authors.initials: DD
authors.lastname: Rubens
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000900:Anti-Bacterial Agents / Q000633:toxicity; D001143:Arousal / Q000502:physiology*; D004195:Disease Models, Animal; D007839:Functional Laterality / Q000187:drug effects / Q000502:physiology; D005839:Gentamicins / Q000633:toxicity; D006935:Hypercapnia / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D051379:Mice; D009068:Movement / Q000187:drug effects / Q000502:physiology; D010991:Plethysmography; D012119:Respiration / Q000187:drug effects; D013997:Time Factors; D015837:Vestibular Diseases / Q000139:chemically induced / Q000503:physiopathology*
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins
keywords: HCVR; IP-Gent; IP-Saline; IT-Gent; IT-Saline; SIDS; Sudden Infant Death Syndrome; TV; V(min); arousal; f(inst); gentamicin; hypercapnic ventilatory response; inner-ear; instantaneous respiratory frequency; intra-peritoneal gentamicin; intra-peritoneal saline; intra-tympanic gentamicin; intra-tympanic saline; minute ventilation; nTV; normalized tidal volume; severe hypoxia–hypercarbia; tidal volume; vestibular
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