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Effect of Vocalization on Tissue Protein Levels in the Acute Vocal Fold Wound

$76,750R03FY2009DCNIH

Vanderbilt University, Nashville TN

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Abstract

DESCRIPTION (provided by applicant): The effect of vocal fold vibration on remodeling of the vocal fold after injury is poorly understood. Clinically, this has resulted in very little agreement with regard to post-operative voice use, voice rest, and lack of a standard of clinical care for patients undergoing phonomicrosurgery. Historically, support for voice rest has been driven by theories that implicate phonation associated trauma with delayed wound healing. In contrast, recent in-vitro studies have shown that gene expression levels of extracellular matrix genes respond favorably to mechanical load. In this application we will 1) Elicit vocalization in a rabbit animal model post-wounding and 2) measure the effects of a 35 minute and 120 minute dose of vocalization on gene expression and tissue levels of the protein products pro-collagen I, collagen, fibronectin, and the glycosaminoglycan hyaluronan prior to epithelial coverage of the wounded vocal fold. We will demonstrate that brain and nerve stimulation techniques provide suitable methods for eliciting vocalization in the rabbit. We hypothesize that 120 minutes of vocalization initiated 72 hours after injury results in significantly elevated levels of fibronectin and collagen, while 35 minutes of vocalization initiated 72 hours after injury results in stable levels of pro-collagen I, collagen, fibronectin, and hyaluronan relative to control. These experiments will result in the development of a rabbit in- vivo phonation model and rationale for a dosing strategy to be used in the next series of studies that will investigate the effects of vocalization initiated after complete epithelial coverage of the wounded vocal fold on gene expression and extracellular matrix deposition. The long-term objective of this line of research is to understand how vocalization influences organization and remodeling of the injured vocal fold. This research program may have an impact clinically by providing data to support a standard of clinical care regarding post- operative voice use. Project Narrative: Scarring is an adverse complication of vocal fold surgery. The effect of voice use on wound healing of the scarred vocal fold is largely unknown. The goal of this research is to understand how voice use influences wound healing in order to provide an evidence-based standard of care regarding post-operative voice use.

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