title: Effect of intratympanic application of aminoglycosides on click-evoked myogenic potentials in Guinea pigs.
abstract: OBJECTIVE
  Although numerous studies have identified damage to the cochlear and vestibular end organs as the primary site of aminoglycoside-induced ototoxicity, the effect on the saccule remains poorly understood, possibly due to lack of monitoring saccular function in experimental animals. Therefore, this study applied three kinds of aminoglycosides into the tympanic space of guinea pigs to examine their toxic impact on the saccule by way of click-evoked myogenic potential test coupled with morphologic assessment.
  
  
  METHODS
  Albino guinea pigs were treated with saline, gentamicin, tobramycin, or amikacin, with 10 animals assigned to each group. Each compound was injected directly overlying but not through the round window membrane on the left ear, with the right ear serving as a control. One week after injection, each animal underwent auditory brain stem response, caloric test, and click-evoked myogenic potential test. Animals were then killed for morphologic assessment through the use of light and electron microscopic examinations.
  
  
  RESULTS
  The animals treated with saline, gentamicin, tobramycin, or amikacin exhibited abnormal auditory brain stem response in 0%, 30%, 100%, and 30% of cases; abnormal caloric responses were found in 0%, 100%, 40%, and 40% of cases; absent click-evoked myogenic potentials were found in 0%, 100%, 30%, and 40% of cases, respectively. Gentamicin and other groups differed significantly in abnormal rates of caloric responses and click-evoked myogenic potentials. Morphologic study of the gentamicin-treated animals confirmed that the absence of click-evoked myogenic potential originated from the lesion in the saccular macula.
  
  
  CONCLUSIONS
  Gentamicin represents the dominant susceptibility of aminoglycoside-induced vestibulotoxicity for eliminating both semicircular canal and saccular functions. This study further confirms the findings of human studies in which the caloric and vestibular evoked myogenic potentials responses were monitored to assess the abolition of vestibular function in patients treated with intratympanic gentamicin injection.
authors.affiliation: Department of Otolaryngology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: An-Shiou
authors.initials: AS
authors.lastname: Day
authors.forename: June-Horng
authors.initials: JH
authors.lastname: Lue
authors.forename: Ting-Hua
authors.initials: TH
authors.lastname: Yang
authors.forename: Yi-Ho
authors.initials: YH
authors.lastname: Young
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods*; D000583:Amikacin / Q000494:pharmacology; D000617:Aminoglycosides / Q000506:poisoning*; D000818:Animals; D002150:Caloric Tests; D004576:Electromyography; D005072:Evoked Potentials, Auditory / Q000187:drug effects*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D005260:Female; D005839:Gentamicins / Q000494:pharmacology / Q000506:poisoning; D006168:Guinea Pigs; D008854:Microscopy, Electron; D011930:Reaction Time / Q000187:drug effects; D012444:Saccule and Utricle / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology* / Q000648:ultrastructure; D012665:Semicircular Canals / Q000187:drug effects / Q000502:physiology; D014031:Tobramycin / Q000494:pharmacology; D014432:Tympanic Membrane / Q000187:drug effects*; D014722:Vestibule, Labyrinth / Q000187:drug effects / Q000502:physiology
chemical_list: D000617:Aminoglycosides; D005839:Gentamicins; D000583:Amikacin; D014031:Tobramycin