title: Drug-induced Defibrinogenation as New Treatment Approach of Acute Hearing Loss in an Animal Model for Inner Ear Vascular Impairment.
abstract: Disturbance of cochlear microcirculation is considered to be the final common pathway of various inner ear diseases. Hyperfibrinogenemia causing increased plasma viscosity is a known risk factor for sudden sensorineural hearing loss and may lead to a critical reduction of cochlear blood flow. The aim of this study was to evaluate the effect of a substantial reduction of plasma fibrinogen levels by drug-induced defibrinogenation for the treatment of acute hearing loss in vivo.
  
  
  
  Acute hearing loss was induced by hyperfibrinogenemia (i.v. injection of 330 mg/kg BW fibrinogen), using a guinea pig animal model. Parameters of cochlear microcirculation and hearing thresholds were quantified by intravital microscopy and evoked response audiometry. After obtaining baseline values, the course of hearing loss and disturbances of microcirculation were investigated under influence of intravenous defibrinogenation therapy (ancrod), corticosteroid, or placebo treatment, using 5 animals/group.
  
  
  
  Acute hyperfibrinogenemia caused hearing loss from 10 ± 7 to 26 ± 10 dB SPL at baseline. Drug-induced reduction of fibrinogen levels showed a significant increase of cochlear microcirculation (1.6-fold) and recovered hearing threshold (11 ± 6 dB SPL). Placebo or corticosteroid treatment had no effect on hearing loss (35 ± 7 dB SPL and 32 ± 18 dB SPL, respectively).
  
  
  
  Acute hyperfibrinogenemia resulted in hearing loss. Drug-induced reduction of elevated fibrinogen levels caused an increase in cochlear blood flow and a decrease in hearing thresholds. Placebo or corticosteroid treatment had no effect. Reduction of plasma fibrinogen levels could serve as a clinical treatment option for acute hearing loss.
authors.affiliation: Department of Otorhinolaryngology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Bernhard G
authors.initials: BG
authors.lastname: Weiss
authors.forename: Mattis
authors.initials: M
authors.lastname: Bertlich
authors.forename: Stephan A
authors.initials: SA
authors.lastname: Bettag
authors.forename: Hendrik
authors.initials: H
authors.lastname: Desinger
authors.forename: Friedrich
authors.initials: F
authors.lastname: Ihler
authors.forename: Martin
authors.initials: M
authors.lastname: Canis
mesh_terms: D000721:Ancrod / Q000494:pharmacology; D000818:Animals; D001300:Audiometry, Evoked Response; D001309:Auditory Threshold / Q000187:drug effects / Q000502:physiology; D003051:Cochlea / Q000098:blood supply* / Q000503:physiopathology; D004195:Disease Models, Animal; D005340:Fibrinogen / Q000009:adverse effects*; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006168:Guinea Pigs; D006319:Hearing Loss, Sensorineural / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D008833:Microcirculation / Q000187:drug effects
chemical_list: D005343:Fibrinolytic Agents; D005340:Fibrinogen; D000721:Ancrod