Validation of Animal Models for Simulation Training in Pediatric Laryngotracheal Reconstruction

Okhovat, Saleh; Milner, Thomas D.; Clement, William Andrew; Wynne, David; Kunanandam, Thushitha

doi:10.1177/0003489419870820

Cited by 17 publications

(19 citation statements)

References 29 publications

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“…Additionally, the literature demonstrates that rabbit larynges exhibit sufficient biological similarity to humans and have been used in molecular and histological studies of the vocal folds [ 43 – 47 ]. The rabbit larynx has also been used to characterize the physiological response to injury secondary to phonation [ 46 , 47 ] or laryngeal and vocal fold surgery [ 48 – 50 ]. The common use of rabbits for laryngeal studies and the relatively small size for handling and housing makes this animal a suitable model for this study.…”

Section: Introductionmentioning

confidence: 99%

RNA sequencing identifies transcriptional changes in the rabbit larynx in response to low humidity challenge

et al. 2020

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Background Voice disorders are a worldwide problem impacting human health, particularly for occupational voice users. Avoidance of surface dehydration is commonly prescribed as a protective factor against the development of dysphonia. The available literature inconclusively supports this practice and a biological mechanism for how surface dehydration of the laryngeal tissue affects voice has not been described. In this study, we used an in vivo male New Zealand white rabbit model to elucidate biological changes based on gene expression within the vocal folds from surface dehydration. Surface dehydration was induced by exposure to low humidity air (18.6% + 4.3%) for 8 h. Exposure to moderate humidity (43.0% + 4.3%) served as the control condition. Ilumina-based RNA sequencing was performed and used for transcriptome analysis with validation by RT-qPCR. Results There were 103 statistically significant differentially expressed genes identified through Cuffdiff with 61 genes meeting significance by both false discovery rate and fold change. Functional annotation enrichment and predicted protein interaction mapping showed enrichment of various loci, including cellular stress and inflammatory response, ciliary function, and keratinocyte development. Eight genes were selected for RT-qPCR validation. Matrix metalloproteinase 12 (MMP12) and macrophage cationic peptide 1 (MCP1) were significantly upregulated and an epithelial chloride channel protein (ECCP) was significantly downregulated after surface dehydration by RNA-Seq and RT-qPCR. Suprabasin (SPBN) and zinc activated cationic channel (ZACN) were marginally, but non-significantly down- and upregulated as evidenced by RT-qPCR, respectively. Conclusions The data together support the notion that surface dehydration induces physiological changes in the vocal folds and justifies targeted analysis to further explore the underlying biology of compensatory fluid/ion flux and inflammatory mediators in response to airway surface dehydration.

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Section: Introductionmentioning

confidence: 99%

RNA sequencing identifies transcriptional changes in the rabbit larynx in response to low humidity challenge

et al. 2020

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“…They are used as clinical and surgical skills training models. For instance, pigs are still commonly used in terminal experiments to practice surgical skills in human medicine (Deonarain et al, 2020;Giménez et al, 2020), and rabbits are used for training neonatal intubation procedures (Okhovat et al, 2020;Ulmer et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Educational use of animals in Europe indicates a reluctance to implement alternatives

Zemanova¹,

Knight

Lybæk³

2021

ALTEX

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Animals have been considered an indispensable tool to teach about the functioning of living organisms, to obtain skills necessary for practicing human and veterinary medicine, as well as for acquiring skills for caring for and conducting experiments on animals in laboratories. However, the efficacy of this practice has been questioned in the last decades and societal views have evolved to put a much larger emphasis on animal welfare and ethics that needs to be reflected in our teaching and training practices. Currently, many alternatives to harmful animal use are available, and it is not clear why thousands of animals continue to be used every year for educational and training purposes. Therefore, this study aimed to identify reasons for the lack of uptake of non-harmful educational and training methods by analysing recently published non-technical summaries in the EU and EEA Member States, and to provide examples of alternatives for specific learning objectives. Results from non-technical summaries from 18 countries spanning the most recent years (2017-2019) revealed that the two main perceived reasons for continued animal use are 1) the necessity of using a living animal for 'proper' learning and 2) the lack of an adequate alternative. We argue that these reasons often do not reflect reality. In conclusion, we consider it is necessary to put a stronger emphasis on engagement with ethical questions that underlie the use of animals and careful consideration of how the learning objectives could be achieved through non-harmful alternatives.

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“…While this may impact functional studies of the larynx, molecular analysis of vocal folds themselves is facilitated by the absence of a secondary complex structure. The rabbit is also validated as a model for vocal fold injury 19 , 20 and recently as a training model for laryngotracheal surgery 21 .…”

Section: Introductionmentioning

confidence: 99%

Recurring exposure to low humidity induces transcriptional and protein level changes in the vocal folds of rabbits

Bailey

Santos

Nascimento

et al. 2021

Sci Rep

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Voice disorders are an important human health condition. Hydration is a commonly recommended preventive measure for voice disorders though it is unclear how vocal fold dehydration is harmful at the cellular level. Airway surface dehydration can result from exposure to low humidity air. Here we have induced airway surface dehydration in New Zealand White rabbits exposed to a recurring 8-h low humidity environment over 15 days. This model mimics an occupational exposure to a low humidity environment. Exposure to moderate humidity was the control condition. Full thickness soft-tissue samples, including the vocal folds and surrounding laryngeal tissue, were collected for molecular analysis. RT-qPCR demonstrated a significant upregulation of MUC4 (mucin 4) and SCL26A9 (chloride channel) and a large fold-change though statistically non-significant upregulation of SCNNA1 (epithelial sodium channel). Proteomic analysis demonstrated differential regulation of proteins clustering into prospective functional groups of muscle structure and function, oxidative stress response, and protein chaperonin stress response. Together, the data demonstrate that recurring exposure to low humidity is sufficient to induce both transcriptional and translational level changes in laryngeal tissue and suggest that low humidity exposure induces cellular stress at the level of the vocal folds.

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Validation of Animal Models for Simulation Training in Pediatric Laryngotracheal Reconstruction

Cited by 17 publications

References 29 publications

RNA sequencing identifies transcriptional changes in the rabbit larynx in response to low humidity challenge

RNA sequencing identifies transcriptional changes in the rabbit larynx in response to low humidity challenge

Educational use of animals in Europe indicates a reluctance to implement alternatives

Recurring exposure to low humidity induces transcriptional and protein level changes in the vocal folds of rabbits

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