Dataset Information

The role of systemic dehydration in vocal fold healing: Preliminary findings.

ABSTRACT:

Rationale

Systemic dehydration negatively alters the expression of vocal fold inflammatory and cell junction markers. These biological changes can have downstream effects on the healing processes of injured vocal folds. In the dermis, reduced hydration prolongs inflammation and delays healing. It is unknown whether this biological effect is observed in vocal fold tissue.

Objective

To investigate the effects of systemic dehydration on vocal fold healing outcomes following acute, bilateral vocal fold injury in a rodent model.

Methods

Eighteen systemic dehydrated and 18 euhydrated adult male Sprague Dawley rats experienced bilateral vocal fold injuries or no injury (N = 9/group). Vocal fold gene expression levels of inflammatory mediators and epithelial cell junction markers were measured 24 h post-injury.

Results

Pro-inflammatory gene markers (IL-1β; TNF-α) were differentially expressed in response to systemic dehydration with vocal fold injury compared to non-injury. Epithelial cell junction markers (Cadherin-3, Desmoglein-1) also exhibited divergent trends following systemic dehydration, but these data were not statistically significant.

Conclusions

Systemic dehydration may affect cellular vocal fold healing processes within 24 h. These findings lay the groundwork for further investigation of how hydration status can affect vocal fold tissue recovery and influence clinical care.

SUBMITTER: Venkatraman A

PROVIDER: S-EPMC9764801 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

The role of systemic dehydration in vocal fold healing: Preliminary findings.

Venkatraman Anumitha A Hawkins Jan J McCain Robyn R Duan Chenwei C Cannes do Nascimento Naila N Cox Abigail A Sivasankar M Preeti MP

Laryngoscope investigative otolaryngology 20221006 6

<h4>Rationale</h4>Systemic dehydration negatively alters the expression of vocal fold inflammatory and cell junction markers. These biological changes can have downstream effects on the healing processes of injured vocal folds. In the dermis, reduced hydration prolongs inflammation and delays healing. It is unknown whether this biological effect is observed in vocal fold tissue.<h4>Objective</h4>To investigate the effects of systemic dehydration on vocal fold healing outcomes following acute, bi ...[more]

PMID: 36544957

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Project description:Clinicians commonly recommend increased hydration to patients with voice disorders. However, effects on clinical voice outcome measures have been inconsistent. Hydration-induced change within different layers of vocal fold tissue is currently unknown. Magnetic Resonance Imaging (MRI) is a promising method of noninvasively measuring water content in vocal folds. We sought to image and quantify changes in water content within vocal fold mucosa and thyroarytenoid muscle after dehydration and rehydration. Excised porcine larynges were imaged using proton density (PD) weighted MRI (1) at baseline and (2) after immersion in one of five hypertonic, isotonic, or hypotonic solutions or in dry air. Larynges dehydrated in hypertonic solutions or dry air were rehydrated and imaged a third time. Scans revealed fluid-rich vocal fold mucosa that was distinct from muscle at baseline. Baseline normalized signal intensity in mucosa and muscle varied by left vs. right vocal fold (p < 0.01) and by anterior, middle, or posterior location (p < 0.0001). Intensity changes in the middle third of vocal fold mucosa differed by solution after immersion (p < 0.01). Hypertonic solutions dehydrated the middle third of mucosa by over 30% (p < 0.001). No difference from baseline was found in anterior or posterior mucosa or in muscle after immersion. No association was found between intensity change in mucosa and muscle after immersion. After rehydration, intensity did not differ by solution in any tissue, and was not different from baseline, but post-rehydration intensity was correlated with post-immersion intensity in both mucosa and muscle (p < 0.05), suggesting that degree of change in vocal fold water content induced by hypertonic solutions ex vivo persists after rehydration. These results indicate that PD-MRI can be used to visualize large mammalian vocal fold tissue layers and to quantify changes in water content within vocal fold mucosa and thyroarytenoid muscle independently.

Project description:BackgroundA considerable body of clinical evidence suggests that systemic dehydration can negatively affect voice production, leading to the common recommendation to rehydrate. Evidence for the corrective benefits of rehydration, however, is limited with mixed conclusions, and biological data on the underlying tissue changes with rehydration is lacking. In this study, we used a rabbit model (n = 24) of acute (5 days) water restriction-induced systemic dehydration with subsequent rehydration (3 days) to explore the protein-level changes underlying the molecular transition from euhydration to dehydration and following rehydration using LC-MS/MS protein quantification in the vocal folds. We show that 5-day water restriction led to an average 4.3% decrease in body weight with relative increases in anion gap, Cl-, creatinine, Na+, and relative decreases in BUN, iCa2+, K+, and tCO2 compared to control (euhydrated) animals. A total of 309 differentially regulated (p < 0.05) proteins were identified between the Control and Dehydration groups. We observed a noteworthy similarity between the Dehydration and Rehydration groups, both well differentiated from the Control group, highlighting the distinct timelines of resolution of the clinical symptoms of systemic dehydration and the underlying molecular changes.SignificanceVoice disorders are a ubiquitous problem with considerable economic and psychological impact. Maintenance of proper hydration is commonly prescribed as a general vocal hygiene practice. There is evidence that dehydration negatively impacts phonation, but our understanding of the state of vocal folds in the context of systemic dehydration are limited, particular from a molecular perspective. Further, ours is a novel molecular study of the short-term impact of rehydration on the tissue. Given the relatively minimal difference in vocal fold proteomic profiles between the Dehydration and Rehydration groups, our data demonstrate a complex physiological response to acute systemic dehydration, and highlight the importance of considering persistent underlying molecular pathology despite the rapid resolution of clinical measures. This study sets a foundation for future research to confirm the nature of potential beneficial outcomes of clinical recommendations related to hydration.

Project description:Whole-body dehydration (i.e., systemic dehydration) leads to vocal fold tissue dehydration. Furosemide, a common diuretic prescribed to treat hypertension and edema-associated conditions, induces systemic dehydration. Furosemide also causes voice changes in human speakers, making this method of systemic dehydration particularly interesting for vocal fold dehydration studies. Our objective was to obtain a comprehensive proteome of vocal folds following furosemide-induced systemic dehydration. New Zealand White rabbits were used as the animal model and randomly assigned to euhydrated (control) or furosemide-dehydrated groups. Systemic dehydration, induced by injectable furosemide, was verified by an average body weight loss of -5.5% and significant percentage changes in blood analytes in the dehydrated rabbits compared to controls. Vocal fold specimens, including mucosa and muscle, were processed for proteomic analysis using label-free quantitation LC-MS/MS. Over 1600 proteins were successfully identified across all vocal fold samples; and associated with a variety of cellular components and ubiquitous cell functions. Protein levels were compared between groups showing 32 proteins differentially regulated (p ≤ 0.05) in the dehydrated vocal folds. These are mainly involved with mitochondrial translation and metabolism. The downregulation of proteins involved in mitochondrial metabolism in the vocal folds suggests a mechanism to prevent oxidative stress associated with systemic dehydration. SIGNIFICANCE: Voice disorders affect different population demographics worldwide with one in 13 adults in the United States reporting voice problems annually. Vocal fold systemic hydration is clinically recognized for preventing and treating voice problems and depends on optimal body hydration primarily achieved by water intake. Herein, we use the rabbit as a translatable animal model, and furosemide as a translatable method of systemic dehydration, to reveal a comprehensive proteomic profile of vocal fold mucosa and muscle in response to systemic dehydration. The significant subset of proteins differentially regulated due to furosemide-induced dehydration offer novel insights into the molecular mechanisms of systemic dehydration in the vocal folds. These findings also deepen our understanding of changes to tissue biology after diuretic administration.

Dataset Information

The role of systemic dehydration in vocal fold healing: Preliminary findings.

Rationale

Objective

Methods

Results

Conclusions

Publications

The role of systemic dehydration in vocal fold healing: Preliminary findings.

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