Development of an In Vivo Model for Eustachian Tube Dysfunction

Abstract

Otitis media is often connected to Eustachian tube dysfunction (ETD). Until now, there was no large animal model available for the examination of new treatment methods such as stents for the Eustachian tube (ET). Thus, the aim of the study was to develop a method to reproducibly induce ETD by injection of fillers and without permanent closure of the ET. Tools for safe injection of hyaluronic acid (HA) in the surrounding of the ET were developed. In ex vivo experiments, HA mixed with Imeron® was injected close to the nasopharyngeal orifice of the ET of blackface sheep. The established depot was visualized using cone beam computer tomography and magnetic resonance imaging, and stents could be placed into the ET. A reliable position of the HA depot was achieved. This method was transferred to in vivo, and middle ear ventilation was investigated by tympanometry. ETD was achieved with amounts of 2.5 mL HA or higher. None of the animals showed any sign of discomfort or complications. The induced ETD lasted for 3 to 13 (maximum observation period) weeks and was also combined with middle ear effusion. A model of ETD based on injection of HA next to the ET was successfully established and is now available to test novel treatment options for ET functionality.

Permanent occlusion of the Eustachian tube: a retrospective study on reopening procedures

“…One of the challenges post-surgery is the possibility of restenosis of the ET. The timing and design of stents for the Eustachian tube remain areas requiring more research and development [ 21 , 22 ]. Lasers, although beneficial, might exacerbate scarring risks.…”

Intravascular Ultrasonography (IVUS)—A Tool for Imaging the Eustachian Tube?

“…To simulate changes in the tissue surrounding the ET, HA was used as a filler to introduce a stenosing depot in the lateral tube wall. Briefly, following the protocol of Oppel et al, 2022 [ 23 ], non-stabilized hyaluronic acid sodium salt from rooster (Sigma-Aldrich Chemie GmbH, Taufkirchen, Germany) was dissolved in isotonic saline solution 0.9% (Isotonic saline solution 0.9% ecoflac plus, B Braun Melsungen AG, Melsungen, Germany) at a concentration of 20 mg/mL and vortexed for 5 min. As a radiographic contrast enhancer, Imeron ® 300 (Bracco Imaging Deutschland GmbH, Konstanz, Germany) (0.2 mL/mL) was added direct during the dissolution.…”

“…For some experiments, SonoVue ® (Bracco International B.V., Amsterdam, Netherlands) was added to the solution directly before the experiment or was injected pure. A depot with a volume of 0.3 mL up to 1.0 mL was generated in the lateral wall of the ET using a special insertion instrument [ 23 ]. During and after this procedure, scans were performed via the IVUS catheter.…”

“…The injection of stabilized HA (Restylane ® LYFT Lidocaine 1 mL; GALDERMA, Lausanne, Switzerland) was performed following the protocol by Oppel et al, 2022 [ 23 ]. Briefly, for local anesthesia, tip swabs soaked with xylometazolinhydrochloride 10 mL (Otriven 0.1%, GlaxoSmithKline Consumer Healthcare GmbH & Co. KG, Munich, Germany) and lidocaine 5 mL (Xylocitin ® -loc 2%, mibe GmbH, Brehna, Germany) were placed for 5 min in both nostrils.…”