Medikamentöse Defibrinogenierung zur Behandlung des akuten Hörverlustes – eine verblindete, placebokontrollierte In-vivo-Studie

Drug-induced defibrinogenation as treatment approach of acute hearing loss in an animal model: a blind, placebo-controlled in-vivo-study

by Stephan Bettag
Doctoral thesis
Date of Examination:2020-11-30
Date of issue:2020-11-26
Advisor:Prof. Dr. Wolfgang Brück
Referee:Prof. Dr. Martin Canis
Referee:Prof. Dr. Michael Koziolek
Referee:Prof. Dr. Rainer Mausberg
Persistent Address: http://dx.doi.org/10.53846/goediss-8328

 

 

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Abstract

English

Sudden hearing loss is one of the most common inner-ear diseases. The underlying pathomechanism is still not fully understood and most often it remains idiopathic. One of its discussed causes is the disturbance of cochlear microcirculation that is either the primary cause but also considered to be the final common pathway of other aetiopathological factors. Fibrinogen affects microcirculation and hyperfibrinogenemia was identified as a risk factor for sudden hearing loss. The present study demonstrated in vivo that acute hyperfibrinogenemia increases hearing threshold. The animal model allows simultaneous measurement of hearing threshold by brainstem evoked response audiometry, and cochlear blood flow by intravital microscopy. Furthermore, by a central venous catheter, blood samples can be taken, and application of medication is possible. A sudden hearing loss was induced by acute hyperfibrinogenemia. Next, in an experimental therapy trial, drug-induced defibrinogenation by ancrod was demonstrated for treatment of this vascular inner ear impairment. Reduction of pathologic fibrinogen levels was followed by an increase of cochlear blood flow, accompanied by a recovery of hearing loss. Placebo treatment had no effect on hearing thresholds or parameters of cochlear microcirculation. Ancrod was already marketed in Europe and Canada for indications like peripheral arterial occlusive disease, deep vein thrombosis, and prophylaxis for thromboembolism. It is safe and easy to monitor by routine laboratory tests measuring plasma fibrinogen level. The reduction of plasma fibrinogen might serve as a future treatment option for acute hearing loss.
Keywords: Fibrinogen; Defibrinogenation; Hearing Loss; Ancrod
 
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