Researchers Develop Clinically Relevant Animal Model for Subglottic Injury

Can a clinically aligned, reproducible model for subglottic injury be developed?

Background: Animal models for subglottic stenosis (SGS) have been invaluable in understanding the underlying mechanisms and in developing new prevention strategies. However, most animal models focus on causing a direct mucosal injury to the subglottic region rather than emulating some of the clinical causes such as long-term intubation and/or oversized endotracheal tubes. Additionally, the methods associated with direct injury models can have constraints due to ethical approval and high mortality rates congruent with the large stenosis induced in these models.

Study design: Prospective randomized control pilot study.

Setting: School of Medicine and Medical Science, University College Dublin; National Children’s Research Centre, Our Lady’s Children’s Hospital, Dublin; Diabetes Research Centre, School of Medicine and Medical Science, Conway Institute, University College Dublin; Our Lady’s Children’s Hospital, Dublin, Ireland.

Synopsis: Eight juvenile (3-month-old) New Zealand White rabbits underwent intubation with a 3-cm length of an endotracheal tube that was one or two sizes above the appropriate tube for the animal. It was held in place for one week and then animals were sacrificed and larynges harvested. Three non-intubated New Zealand White rabbits served as controls. Histological examination of specimens from animals intubated for one week indicated significant pathology. The experiments revealed that three parameters were necessary for survival of animals: 1) weight above 2.1 kg, 2) intubation duration of one week, and 3) placement of tube below vocal cords. The authors noted that reproducibility is a key strength of their model.

Bottom line: The model developed by the authors replicates clinical SGS that occurs when long-term intubation/oversized tube placement occurs and when the pressure within the tube is greater than within the surrounding capillaries, resulting in ischemic necrosis.

Reference: Kelly NA, Murphy M, Giles S, Russell JD. Subglottic injury: a clinically relevant animal model. Laryngoscope. 2012;122(11):2574-2581.