PROJECT SUMMARY / ABSTRACT: The goal of this research is to systematically investigate the contribution of the compliance levels of the aortic arch and pulmonary artery to onset of impaired function of the recurrent laryngeal branch (RLN) of the vagus nerve associated with unilateral vocal fold paralysis (UVP). The RLN provides sensorimotor innervation to the muscles that control the vocal folds within the larynx. Vocal fold function is 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. Although surgery is the most common etiology of UVP, approximately 12-42% of those diagnosed with UVP have no known cause (i.e. idiopathic). Prior work studying idiopathic onset of UVP in horses identified nerve changes and characteristics indicative of chronic compression on the RLN near the aortic arch. Our team recently identified that individuals with iUVP exhibited significantly higher aortic arch compliance than age- and gender-matched controls as a possible contributing factor in iUVP. This finding supported our hypothesis that RLN stress and strain levels associated with aortic arch dynamic diameter changes could impact RLN function. Similar patterns in pulmonary artery compliance levels were also identified in the same group of those with iUVP compared to normal controls suggesting a systemic change in vascular compliance. Given that the left RLN is most commonly associated with iUVP, we hypothesize that increased compliance levels in large- diameter blood vessels adjacent to the RLN (i.e. aortic arch and pulmonary artery) can impair RLN function due to excessive stress and strain levels that compromise the nerve's protective layers of connective tissues resulting in damaged nerve fibers. The goal of this project is to investigate the level of compliance change in the aorta associated with impaired RLN function in pigs. We will also expand imaging of the aortic arch and pulmonary artery to include the right subclavian artery to determine whether vascular compliance levels generally differ between those with iUVP compared to controls. In addition, we will compare compliance levels between a large-diameter vessel (aortic arch) and a small-diameter vessel (right subclavian artery) associated with the RLN between human subjects with iUVP and matched normal controls. Outcomes will eludicate whether the size of vessel explains the predominance of left-sided iUVP. Systematic comparison of medical, environmental, and genetic historical data between human subject groups will also enable identification of risk factors associated with hypercompliance of the vasculature. Outcomes of this project will elucidate the role of vascular hypercompliance on impaired RLN function in those with iUVP and determine co-morbidities and risk factors that could lead to prevention or alternative treatment approaches for iUVP in the future.

PROJECT NARRATIVE / RELEVANCE TO PUBLIC HEALTH Outcomes of this project will determine the degree to which large-diameter blood vessel (i.e. aortic arch and pulmonary artery) compliance levels impact function of the recurrent laryngeal nerve resulting in idiopathic unilateral vocal fold paralysis. We will also determine co-morbidities and risk factors associated with these vascular changes that could lead to prevention or alternative treatment approaches for onset of unilateral vocal fold paralysis in the future.