THE EFFECTS OF HYDRATION STATES ON VOCAL FOLD PATHOBIOLOGY, BIOMECHANICS, AND HEMODYNAMICS

Vocal fold vibration results in voice production. Optimal hydration levels contribute to self-sustained vocal fold vibration and preservation of voice quality. Adequate hydration is implicated as a factor in maintaining voice and preventing voice problems. Voice problems affect up to one third of adults during their lifetime. But whether altered hydration state adversely affects vocal fold biology and biomechanics is still unclear. To untangle the effects of systemic dehydration on vocal fold biology, we developed a water restriction protocol on lab animals that can translate to humans. Our results showed that dehydration induced by restricted water access downregulated the gene expression of IL-1α and desmoglein-1, upregulated the gene expression level of hyaluronidase-2, and downregulated hyaluronic acid (HA). Clinically, hydration treatments are hypothesized to maintain the viscoelastic properties of vocal folds. However, our understanding of the relationship between vocal fold tissue hydration level and biomechanical properties is still evolving. To investigate the effects of dehydration on biomechanical properties we used an ex vivo experimental design. We hypothesized that the optimal stiffness of vocal folds would be impacted after dehydration via losing both water and HA, but that the stiffness properties would recover through rehydration. To test this hypothesis, we experimentally treated porcine vocal fold samples using two different approaches: 1) immersion in hypertonic solution (15% NaCl in ddH2O) and PBS sequentially to mimic dehydration and rehydration, and 2) incubation with hyaluronidase (Hyal) to mimic HA loss during dehydration. Our results showed that loss of water increased tissue stiffness and could be recovered through rehydration in a certain degree. In addition, loss of HA increased tissue stiffness. In While dehydration decreases total body blood volume, different tissues and organs of the body may be impacted in different ways from dehydration. Therefore, it is important to investigate the hemodynamic alterations during changes to hydration status. Magnetic resonance angiography (MRA) and ultrasound imaging were employed to identify the delicate vascular geometry and hemodynamics of the laryngeal blood supply. Animals underwent both MRA and ultrasound imaging at baseline, dehydration and rehydration time points. Our results showed that dehydration impacted the blood supply to larynx. This blood supply was restored through rehydration treatment. Overall, this research has been successful in establishing a mild dehydration animal model, providing evidence from gene and protein levels that dehydration affects cytokine production and extracellular matrix components (ECM) in vocal fold, demonstrating the vocal fold tissue biomechanical behavior after dehydration and loss of HA, and offering a combination application of MRA and ultrasound imaging to study vascular geometry and hemodynamics of the blood supply to the vocal fold region.