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DOI 10.1101/2025.06.27.662000

Медицинская библиотека · bioRxiv : the preprint server for biology · 2025

Development of a Clinically Relevant Rabbit Model of Acute Laryngeal Injury.

Stepp Ryan, Ali Naushin, Rodriguez Areli A, Nicklow Ethan, Thornton Noah, Reddy Adithya, Kenny Hannah, Cottler Patrick S, Griffin Donald R, Daniero James J

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Аннотация

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 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 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.

RESULTS

Injured 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 (1.93mm 2 vs. 0.17mm 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: Level III.

Для цитирования: Stepp Ryan, Ali Naushin, Rodriguez Areli A, Nicklow Ethan, Thornton Noah, Reddy Adithya, Kenny Hannah, Cottler Patrick S, Griffin Donald R, Daniero James J. Development of a Clinically Relevant Rabbit Model of Acute Laryngeal Injury.. bioRxiv : the preprint server for biology. 2025. DOI: 10.1101/2025.06.27.662000.
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