Development of a Clinically Relevant Rabbit Model of Acute Laryngeal Injury

Stepp, R.; Ali, N.; Rodriguez, A. A.; Nicklow, E.; Thornton, N.; Reddy, A.; Kenney, H.; Cottler, P. S.; Griffin, D. R.; Daniero, J. J.

doi:10.1101/2025.06.27.662000

bioRxiv · 10.1101/2025.06.27.662000

Development of a Clinically Relevant Rabbit Model of Acute Laryngeal Injury

Stepp, R.·Ali, N.·Rodriguez, A. A.·Nicklow, E.·Thornton, N.·Reddy, A.·Kenney, H.·Cottler, P. S.·Griffin, D. R.·Daniero, J. J.

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Abstract

ObjectivesAcute 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 serve as a reproducible injury suitable for the evaluation of therapeutic interventions. MethodsAn 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 one hour to mimic intubation-associated trauma and pressure ischemia. Laryngoscopy and laryngeal harvest were performed two weeks post-injury for histologic and immunofluorescent evaluation. ResultsInjured rabbits demonstrated an eight-fold increase in posterior glottic thickness (1.57mm vs. 0.19mm in controls; p=0.0004) and eleven-fold increase in collagen content (1.93mm2 vs. 0.17mm2; 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. ConclusionsThe 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 EvidenceLevel III

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Stepp, R., Ali, N., Rodriguez, A. A., Nicklow, E., Thornton, N., Reddy, A., Kenney, H., Cottler, P. S., Griffin, D. R., Daniero, J. J.. 2025-07-02. Development of a Clinically Relevant Rabbit Model of Acute Laryngeal Injury. https://doi.org/10.1101/2025.06.27.662000

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