Investigating the pathobiology of vocal fold dehydration

Abstract

Optimal hydration is thought to be necessary for maintaining healthy vocal folds. Whether in vivo systemic dehydration induces vocal fold dehydration is not fully understood. Furthermore, whether systemic rehydration of vocal folds following systemic dehydration has not been investigated. Due to the ubiquitous nature of water in the body, the complex physiological mechanisms in place to maintain body hydration, and the often insensitive markers of hydration status, we set out to design an animal model to study how systemic dehydration affects the vocal folds. The objectives of this study include (1) identifying the optimal animal model for investigations of systemic dehydration and systemic rehydration, (2) developing a reliable and physiologically relevant methodology of systemic dehydration, (3) developing markers of systemic dehydration and (4) demonstrating whether systemic dehydration induces vocal fold dehydration through a combination of methodologies. Sprague Dawley (SD) rats (males and females) and New Zealand White rabbits (males) were used for systemic dehydration and rehydration studies. Rats were systemically dehydrated to an average of 10% reduction in body weight by withholding water. Rabbits were given 5 mg/kg furosemide IP to induce a moderate level of systemic dehydration based on 5% body weight loss. Body weight loss due to dehydration was corroborated by parameters of hemoconcentration. Proton‐density weight MRI at variable dehydration states, genomic analysis of vocal folds, and histopathology were all investigated to determine effects of systemic dehydration. Proton‐density weighted MR imaging can be used to demonstrate that systemic dehydration reliably induces vocal fold dehydration as detected by signal intensity changes. These changes however, are only detected at high body weight loss levels (> 6% body weight loss). Acute episodes of systemic dehydration do not produce reliable, adverse pathological changes to the vocal folds as assessed by histopathology and gene expression studies. Access to water does not induce rehydration if defined by body weight. There are challenges in inducing physiologically‐relevant systemic dehydration and developing a robust and reliable animal model to study the pathobiology of vocal fold dehydration. A combination of techniques are necessary to confirm that dehydration, in an otherwise healthy animal, is occurring; and that dehydration of the body is dehydrating the vocal folds. The sequelae of chronic versus acute dehydration, and systemic dehydration versus surface dehydration also need to be parsed out. Support or Funding Information NIH R01DC015545