title: Effects of furosemide applied chronically to the round window: a model of metabolic presbyacusis.
abstract: Hearing thresholds in elderly humans without a history of noise exposure commonly show a profile of a flat loss at low frequencies coupled with a loss that increases with frequency above approximately 2 kHz. This profile and the relatively robust distortion product otoacoustic emissions that are found in elderly subjects challenge the common belief that age-related hearing loss (presbyacusis) is based primarily on sensory-cell disorders. Here, we examine a model of presbyacusis wherein the endocochlear potential (EP) is reduced by means of furosemide applied chronically to one cochlea of a young gerbil. The model results in an EP that is reduced from 90 to approximately 60 mV, a value often seen in quiet-aged gerbils, with no concomitant loss of hair cells. Resulting measures of cochlear and neural function are quantitatively similar to those seen in aging gerbils and humans, e.g., a flat threshold loss at low frequencies with a high-frequency roll-off of approximately -8.4 dB/octave. The effect of the EP on neural thresholds can be parsimoniously explained by the known gain characteristics of the cochlear amplifier as a function of cochlear location: in the apex, amplification is limited to approximately 20 dB, whereas in the base, the gain can be as high as 60 dB. At high frequencies, amplification is directly proportional to the EP on an approximately 1 dB/mV basis. This model suggests that the primary factor in true age-related hearing loss is an energy-starved cochlear amplifier that results in a specific audiogram profile.
authors.affiliation: Department of Otolaryngology and Head-Neck Surgery, Medical University of South Carolina, Charleston, South Carolina 29425, USA. schmiera@musc.edu
authors.forename: Richard A
authors.initials: RA
authors.lastname: Schmiedt
authors.forename: Hainan
authors.initials: H
authors.lastname: Lang
authors.forename: Hiro-oki
authors.initials: HO
authors.lastname: Okamura
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Schulte
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects; D003051:Cochlea / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005665:Furosemide; D005849:Gerbillinae; D015918:Infusion Pumps, Implantable; D008297:Male; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects; D011304:Presbycusis / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D012405:Round Window, Ear / Q000187:drug effects* / Q000473:pathology; D013995:Time
chemical_list: D005665:Furosemide