Biochemical basis of vocal fold mobilization after microflap surgery in a rabbit model

Abstract

Objectives/Hypothesis To investigate phonation-related extracellular matrix (ECM) changes in the vocal fold lamina propria after microflap surgery using an in vivo rabbit phonation model. Study Design Prospective animal study. Methods Twenty-four New Zealand White rabbits were used in this study. Quantitative polymerase chain reaction and immunohistochemistry were used to investigate alterations in vocal fold ECM proinflammatory and profibrotic gene, and protein expression from a control group of animals receiving a microflap without phonation and a separate group of animals receiving experimentally induced phonation on postmicroflap days 0, 3, and 7. Results IHC demonstrated the highest concentration of CD45 in vocal folds on postoperative day 0. Staining for CD45 was absent by postoperative day 7, with no differences in CD45 staining between groups. Fibronectin gene expression increased significantly on postoperative day 3 in the control and experimentally induced phonation groups, with maximal staining of fibronectin around the microflap incision on postoperative day 7. No alterations in cyclooxygenase-2, interleukin-1β, and transforming growth factor-β1 gene expression were observed between groups. Conclusions Results of the present study revealed an acute inflammatory response in the vocal fold at the time of microflap (day 0) and up to 3 days post-microflap. By post-operative day 3, staining of CD45 positive cells decreased, with essentially no evidence of inflammation by post-operative day 7. With the end of the acute inflammatory response occurring around day 3, these data may provide support for mobilizing tissue after inflammation has subsided and the process of active tissue remodeling has ensued (days 3–7).

Recovery of vibratory function after vocal fold microflap in a rabbit model

“…These early repair events may influence weight, tension, and stiffness of the vocal fold after microflap and result in a transient disruption in vibration symmetry. These impairments in vibration up to day 3 are consistent with known changes that take place during wound healing of the injured vocal fold, including increased deposition of fibronectin …”

“…These impairments in vibration up to day 3 are consistent with known changes that take place during wound healing of the injured vocal fold, including increased deposition of fibronectin. 21,22 Fibronectin acts as a chemoattractant for monocytes, fibroblasts, and endothelial cells, helping guide these cells to the site of injury and providing a substrate for the migration and adhesion of these cells within the extracellular matrix. 23 Thus, the increased cellular infiltrate and activity associated with the first 3 days of tissue repair may provide an explanation for the impairments in vibration noted during this period.…”

Recovery of Vocal Fold Epithelium after Acute Phonotrauma

“…These findings are consistent with previous experiments in our laboratory, showing return of vibratory function and attenuation of the inflammatory process by day 3, with evidence of active tissue remodeling 3–7 days after microflap. 22,23 …”

Structurally and functionally characterized in vitro model of rabbit vocal fold epithelium

“…What remains unknown is how alterations in epithelial barrier morphology and integrity impact epithelial permeability and tissue function. We have in our previous work investigated the role of the epithelium in homeostatic regulation of the vocal fold and protection of the tissue from injury using in vivo animal models (Kojima et al, 2014a, 2014b; Mitchell et al, 2014; Rousseau et al, 2011). What remains is a need for an in vitro system to complement these investigations and provide a tool for identification, rapid screening, and preclinical testing of pharmacological treatments for vocal fold disorders prior to in vivo animal testing and human clinical trials.…”