Chronical electrical stimulation for treatment of aged voice

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Age related weakening of the voice has long been neglected, but gained consideration lately, as vocal endurance is essential in many professions up to higher ages. The noticeable glottal gap and vocal fold (VF) bowing are the most prominent video-laryngoscopic findings in these patients and are mainly related to the atrophy of the thyroarytenoid muscle (TAM). For the proposed project, we hypothesize that functional electrical stimulation (FES) of the recurrent laryngeal nerves (RLN) will counteract age related laryngeal muscular atrophy. Based on previous work we hypothesize in particular that FES will lead to an increase of muscle fiber diameters, and an upregulation of molecular markers of muscle hypertrophy with no subsequent changes of the fibre type distribution. An increase of muscle fibre diameters will lead to an increase of the volume of the TAM, thus diminishing the glottal gap. We furthermore hypothesize that the changes elicited by FES will lead to significantly improved phonatory characteristics being observable in improved laryngeal dynamics and acoustics as assessed by the phonatory ex-vivo experiments.FES will be done for the first time bilaterally in an aged in-vivo ovine model. During surgery, stimulation electrodes will be placed near the common trunk of the RLN before entering the larynx and will be connected to a laryngeal pacing implant located at the neck. Predesigned training patterns will be automatically delivered and repeated every second day for eleven weeks, once the implant was programmed, thus no further anaesthesia or sedation will be necessary during the training, or follow-up endoscopies. After euthanasia outcome parameters will be evaluated in a multi-modal based setting, reaching from the cellular/molecular (immuno-histology, gene expression, signalling pathways) to the anatomical level (micro CT scans/3D-reconstructions) and will comprise important functional testing (phonatory ex-vivo experiments).The proposed project will be pursued in a joint action combining the expertise of Assoc. Prof. Dr. Markus Gugatschka (Medical University Graz, Austria) and Prof. Dr. Michael Döllinger (Friedrich-Alexander University Erlangen-Nürnberg, Germany). While the group of Assoc. Prof. Gugatschka will perform all tasks related to implantation surgery and follow-up, as well as assessing the outcome parameters of FES on a molecular/cellular and anatomical level, the group of Prof. Döllinger will perform ex-vivo phonatory experiments. Combining molecular, histological, anatomical and functional outcome parameters in such a model is a crucial, yet an unmet goal and will create an unprecedented set of data. By direct stimulation of the RLN we preserve the natural anatomy and integrity of the larynx resp. the VF and can counteract directly the underlying reason of presbyphonia. Before going into clinical trials, experiments of this kind in large animal models are indispensable.