DESCRIPTION (provided by applicant): The goal of this research is to develop a computational model of the biomechanical properties of the "packaging," or connective tissues of the recurrent laryngeal branch (RLN) of the vagus nerve to formulate their role in the onset of unilateral vocal fold paralysis (UVP). The vocal folds are important for protection of the airway during swallowing, the regulation of breathing, and for voice production. Individuals with UVP frequently experience choking while eating, difficulty breathing, and difficulty speaking. The majority of individuals diagnosed with UVP are older than 45 years of age. The most common onset of UVP occurs related to surgery with the second most common onset (12-42%) having no known cause (i.e. idiopathic). Surgical etiology of UVP is associated with nerve or nerve tissue damage suffered during or possibly after surgery. Previous work studying idiopathic onset of UVP in horses suggested that chronic compression to the RLN occurred near the aortic arch or inferior trachea. In fact, recent research has shown that individuals with idiopathic UVP may have damage to the RLN at the level of the aortic arch related to a thoracic aneurysm. An aneurysm, or alternatively, increased aortic compliance, would impose increased stretch and compression to the RLN where it is adjacent to the aorta that can impair nerve function. Our recent studies have found differences in the composition of the RLN connective tissues between its location within the neck bilaterally and the portion of the left RLN within the thorax, including the aortic arch region. These findings support Sunderland's theory that connective tissue patterns within peripheral nerves may develop in response to environmental forces to which the nerve is exposed. In addition, differences in the quantity and composition of the RLN were demonstrated between piglets and young adult pigs and between middle age adults and elderly humans indicating that connective tissue changes continue with aging. Given that UVP occurs more often in older than younger humans and animals suggests the need to consider age-related connective tissue changes as a potential contributing factor. The purpose of the proposed research is to develop a computational model of RLN connective tissues that will be used to test for differences in forces imposed on the RLN in subjects with and without UVP. This model will also be used to conduct simulations to predict the degree of stretch or compression necessary to cause damage to RLN connective tissues leading to nerve impairment such as might occur related to the surgical etiology. Development of this model using both pig and human RLN tissues allows for comparison of the similarities and differences between these species so that outcomes from future investigation of predicted levels of RLN tissue deformation necessary to cause onset of UVP using a pig model can be generalized to people.

Outcomes of this research may elucidate the role of RLN connective tissue changes in idiopathic onset of UVP with aging and related to surgery. This model is vital for formulating predictions of the typical ranges of RLN stress and strain in response to physiologic levels of tensile (i.e., stretch) and compressive loading. These predictions will be used in future investigations using an animal model to test hypotheses regarding levels of stress and strain necessary to cause RLN impairment.