Assessing Structural and Physiologic Laryngeal Changes in Response to Systemic Dehydration in a Rabbit Model
Kimball, Emily Elizabeth
While the impact of various voice disorders on patient quality of life has been well characterized, the mechanisms leading to the development of voice disorders are not well understood. There is anecdotal evidence that systemic dehydration is associated with an increased risk of vocal pathology; however, structural and molecular changes within the vocal fold tissue are not well described. The goal of the current study was to characterize these physiologic changes using an in-vivo rabbit model. Twelve rabbits were divided between a control condition and a 72-hour water withholding condition. Blood was collected for analysis every 8 hours during the study in both dehydrated and control animals, and blood plasma analysis was completed every 24 hours. At the end of the 72 hours, the larynges were harvested for structural and gene expression analysis. Structural analysis included measurement of subglottic laryngeal gland size, lamina propria depth, and lamina propria vascularity. Gene expression analysis included the inflammatory marker IL-17, the blood flow marker Endothelial Nitric Oxide Synthase, and the vasoconstriction marker Endothelin 1. Dehydrated animals averaged a decrease in body weight of approximately 10% over the 72 hours, and a significant increase in hematocrit in the dehydrated group compared to the controls confirmed a systemic change in physiology in response to acute dehydration (p<0.0001). Further structural analysis found no significant differences in gland size, lamina propria depth, or lamina propria vascularity between the two groups (p=0.46, p=0.67, p=62 respectively). Gene expression analysis showed a drastic downregulation of all three evaluated genes in the dehydrated group compared to the controls. Acute dehydration was sufficient to elicit a systemwide physiologic response in the rabbit model, but no changes in vocal fold structure were identified. It is likely that an acute dehydration model did not allow sufficient time for structural remodeling to occur. Further, the gross changes to gene expression suggest an overall dip in basal metabolic functioning in the dehydrated tissue. Future studies should utilize a more chronic dehydration model to detect more subtle and long-term vocal fold changes associated with dehydration.