A Novel Murine Model of Acute Laryngeal Injury After Intubation.

Abstract

OBJECTIVE(S): Acute laryngeal injury (ALgI) occurs in over 50% of patients after intubation and mechanical ventilation and is associated with significantly worse voice, breathing, and swallowing outcomes. Currently, there are no small animal models for the study of ALgI and its progression to glottic stenosis. The objective of this study was to develop and validate a novel murine model of ALgI. METHODS: Thirty adult C57BL/6 mice underwent chemomechanical injury to the posterior glottis, and 16 control mice did not undergo injury. Glottic injury was performed under endoscopic guidance using a bleomycin-dipped wire brush. Mice underwent repeat endoscopy at 14- or 21-days following injury, and the maximal interarytenoid angle during respiration was quantified using ImageJ to evaluate glottic mobility. Histologic and gene expression analyses were performed on larynges from each group. RESULTS: The interarytenoid angle of injured mice was significantly reduced compared to controls at both 14 (35.3&#xb0; vs. 68.0&#xb0;, p&#x2009;=&#x2009;0.016) and 21&#x2009;days post-injury (34.5&#xb0; vs. 68.0&#xb0;, p&#x2009;<&#x2009;0.001). There was a significant increase in posterior glottic thickness in injured compared to control mice at 21 (132.5 vs. 53.9, p&#x2009;<&#x2009;0.001) but not 14&#x2009;days post-injury (90.4 vs. 53.9, p&#x2009;=&#x2009;0.1535). Trichrome staining and RT-qPCR demonstrated collagen upregulation in the posterior glottis of injured mice. CONCLUSION: Chemomechanical injury to the posterior glottis produces a novel murine model of ALgI. This safe, reliable, and feasible model lays the foundation for future translational study of ALgI and its progression to glottic stenosis. LEVEL OF EVIDENCE: N/A animal study.