Development of a Clinically Relevant Rabbit Model of Acute Laryngeal Injury

建立具有临床意义的兔急性喉损伤模型

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Abstract

OBJECTIVES: Acute laryngeal injury (ALgI) is created as a result of endotracheal tube pressure ulcer formation leading to fibrosis and inflammation. This condition often leads to airway obstruction and voice and swallowing dysfunction. This study demonstrates a reliable animal model of ALgI to reproduce the acute wound process seen clinically, to explore the pathophysiology of this disease process, and to serve as a reproducible injury suitable for the evaluation of therapeutic interventions. METHODS: An ALgI model was developed in New Zealand White rabbits using precise mucosal stripping of the posterior larynx, followed by intubation with an oversized 4.0 endotracheal tube for 1 h to mimic intubation-associated trauma and pressure ischemia. Laryngoscopy and laryngeal harvest were performed 2 weeks post-injury for histologic and immunofluorescent evaluation. RESULTS: Injured rabbits demonstrated an eightfold increase in posterior glottic thickness (1.57 vs. 0.19 mm in controls; p = 0.0004) and an 11-fold increase in collagen content (1.93 vs. 0.17 mm(2); p = 0.005). Collagen subtype analysis revealed a shift toward active collagen within the injured larynx compared to the uninjured, with increased Type III Collagen (69.0% vs. 26.1%; p < 0.0001) and reduced Type I Collagen (27.2% vs. 73.9%; p < 0.0001) in the posterior glottis, consistent with the proliferative phase of wound healing. Collagen fiber alignment analysis demonstrated increased coherency in injured tissues (0.36 vs. 0.21; p = 0.023), indicating early organized collagen formation consistent with scar formation within the posterior glottis. CONCLUSIONS: The model offers a robust platform for studying the acute pathogenesis of laryngeal injury and for testing the treatment options in the management of ALgI. LEVEL OF EVIDENCE: 3.

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