title: Differential effects of salicylate, quinine, and furosemide on Guinea pig inner and outer hair cell function revealed by the input-output relation of the auditory brainstem response.
abstract: BACKGROUND
  Sensory hearing loss is predominantly caused by the destruction of cochlear outer hair cells (OHCs), inner hair cells (IHCs), or spiral ganglion cells (SGCs). There have been a number of attempts to differentiate between these etiologies of hearing loss, using various psychoacoustic and physiologic paradigms.
  
  
  OBJECTIVE
  Here we investigate the potential of the auditory brainstem response (ABR) input/output function for such differential diagnosis. On the basis of the saturation of the OHC-based cochlear amplifier, it was hypothesized that selective impairment of OHCs would reduce ABR amplitudes at low to moderate but not at high sound levels. Selective impairment of IHCs or SGCs would reduce ABR amplitudes more or less uniformly across sound level. Finally, a mix of OHC and IHC or SGC impairment would reduce ABR amplitudes at all sound levels but less so at high levels depending on the relative contribution of OHC impairment to the hearing loss.
  
  
  METHODS
  To test these hypotheses, normal-hearing adult guinea pigs were intravenously injected with either salicylate, furosemide, or quinine, under ketamine anesthesia. ABRs, as well as distortion-product otoacoustic emissions (DPOAEs), were measured as a function of the sound stimulus level before and after drug injection.
  
  
  RESULTS
  Following salicylate injection, ABR amplitudes were reduced only at low-moderate stimulus levels. Following furosemide or quinine injection, ABR amplitudes were reduced at all levels but less so at high ones. This is in accord with the expectation that acute salicylate administration selectively affects the OHCs, while furosemide and quinine affect both OHCs and IHCs/SGCs. Such differential diagnosis was not possible solely on the basis of DPOAE amplitudes, which were unchanged at high stimulus levels after the injection of each of the three drugs. Comparison of ABR and DPOAE threshold shifts could also differentiate the effects of salicylate from those of furosemide and quinine but could not, for example, unequivocally point to salicylate's selective impairment of OHCs.
  
  
  CONCLUSIONS
  ABR amplitudes appear suitable for differentiating between damage to OHCs and IHCs/SGCs, at least in a controlled experimental setting where pre- and postmanipulation data are available. This could be useful for noninvasively testing the effects of drugs or acoustic overstimulation on the cochlea, at least in the laboratory. Clinical applicability would seem to be limited by the high variability in ABR amplitudes among normal-hearing humans but might be feasible in the future if regular ABR testing entered into routine clinical practice.
authors.affiliation: Center for Hearing and Communication Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm. mpienkow@ucalgary.ca
authors.forename: Martin
authors.initials: M
authors.lastname: Pienkowski
authors.forename: Mats
authors.initials: M
authors.lastname: Ulfendahl
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000633:toxicity; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity; D004195:Disease Models, Animal; D004232:Diuretics / Q000633:toxicity; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects*; D005260:Female; D005665:Furosemide / Q000633:toxicity*; D006168:Guinea Pigs; D006199:Hair Cells, Auditory, Inner / Q000187:drug effects / Q000502:physiology; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects / Q000502:physiology; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology; D008297:Male; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects; D011803:Quinine / Q000633:toxicity*; D012459:Salicylates / Q000633:toxicity*; D013136:Spiral Ganglion / Q000187:drug effects / Q000502:physiology
chemical_list: D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004232:Diuretics; D012459:Salicylates; D005665:Furosemide; D011803:Quinine