A Bama Minipig Model of Laryngopharyngeal Reflux and the Change of Laryngopharyngeal Mucosal Ultrastructure

Background/Aims To establish an animal model of laryngopharyngeal reflux (LPR) and study the effect of LPR on the laryngopharyngeal mucosal ultrastructure. Methods Ten Bama minipigs were randomly divided into control group and stent group. Every pig underwent endoscope, and baseline pH was monitored for 4 hours at laryngopharynx and distal esophagus, then specimens from laryngopharyngeal mucosa were biopsied. For the control group, these procedures were repeated on the 14th day. In the stent group, a custom-designed esophageal stent suit was implanted into esophagus, laryngopharyngeal and distal esophageal pH monitoring lasted for 2 hours, then stent suit was removed 3 days later. At last, the same procedures were done as the control group on the 14th day. Specimens were observed under transmission electron microscope to measure the intercellular space and desmosome number. Results In the control group, there was no laryngopharyngeal reflux on the first day and 14th day. Before the stent was implanted, there was also no laryngopharyngeal reflux in the stent group. In both 2 hours and 14 days after stent implantation, the num -ber of reflux, reflux time, and percentage time of pH < 4.0 were significantly increased (P < 0.05) in the stent group. There was no difference in intercellular space and desmosomes in the control group between baseline and 14th day. In the stent group, intercellular space of laryngopharyngeal mucosa was significantly increased (0.37 μm vs 0.96 μm, P = 0.008), and the number of desmosomes was significantly decreased (20.25 vs 9.5, P = 0.003). Conclusions A Bama minipig model of LPR was established by implanting a custom-designed stent suit. LPR might destroy the laryngophar yngeal mucosal barrier.

[1]  Xiong-Fei Pan,et al.  Interventions for dysphagia in oesophageal cancer. , 2014, The Cochrane database of systematic reviews.

[2]  Lin Lin,et al.  Accuracy of diagnosing gastroesophageal reflux disease by GerdQ, esophageal impedance monitoring and histology , 2014, Journal of digestive diseases.

[3]  D. Hess,et al.  Development and characterization of a Yucatan miniature biomedical pig permanent middle cerebral artery occlusion stroke model , 2014, Experimental & Translational Stroke Medicine.

[4]  Jean‐Pierre Amorij,et al.  Minipigs as an animal model for dermal vaccine delivery. , 2014, Comparative medicine.

[5]  C. Yi,et al.  Relevance of ineffective esophageal motility to secondary peristalsis in patients with gastroesophageal reflux disease , 2014, Journal of gastroenterology and hepatology.

[6]  S. Gonlachanvit,et al.  Gastroesophageal reflux symptoms in typical and atypical GERD: Roles of gastroesophageal acid refluxes and esophageal motility , 2014, Journal of gastroenterology and hepatology.

[7]  C. Silver,et al.  Relationship between reflux and laryngeal cancer , 2013, Head & neck.

[8]  G. Zeng,et al.  Single Intraperitoneal Injection of Monocrotaline as a Novel Large Animal Model of Chronic Pulmonary Hypertension in Tibet Minipigs , 2013, PloS one.

[9]  Jacqui Allen,et al.  Laryngopharyngeal reflux and GERD , 2013, Annals of the New York Academy of Sciences.

[10]  P. Malfertheiner,et al.  Histomorphological differentiation of non‐erosive reflux disease and functional heartburn in patients with PPI‐refractory heartburn , 2013, Alimentary pharmacology & therapeutics.

[11]  Tianyu Zhang,et al.  Dilated intercellular space in the larynx and esophagus of a rabbit reflux model. , 2013, Auris, nasus, larynx.

[12]  S. Azar,et al.  Prevalence of laryngopharyngeal reflux disease in patients with diabetes mellitus. , 2013, Journal of voice : official journal of the Voice Foundation.

[13]  C. Yi,et al.  Relevance of Ultrastructural Alterations of Intercellular Junction Morphology in Inflamed Human Esophagus , 2013, Journal of neurogastroenterology and motility.

[14]  M. Fox,et al.  Upper esophageal sphincter and esophageal motility in patients with chronic cough and reflux: assessment by high-resolution manometry. , 2013, Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus.

[15]  H. Cocks,et al.  Mucosal changes in laryngopharyngeal reflux—prevalence, sensitivity, specificity and assessment , 2013, The Laryngoscope.

[16]  S. Cirera,et al.  Characterisation of Gut Microbiota in Ossabaw and Göttingen Minipigs as Models of Obesity and Metabolic Syndrome , 2013, PloS one.

[17]  筒井 英明 Esophageal motor dysfunction plays a key role in GERD with globus sensation : analysis of factors promoting resistance to PPI therapy , 2013 .

[18]  B. Jobe,et al.  Proximal reflux as a cause of adult-onset asthma: the case for hypopharyngeal impedance testing to improve the sensitivity of diagnosis. , 2013, JAMA surgery.

[19]  Kunio Suzuki,et al.  [A clinical case of the esophagogastric malignancy palliated with covered metallic stent with anti-reflux mechanism]. , 2011, Gan to kagaku ryoho. Cancer & chemotherapy.

[20]  Yu-lan Liu,et al.  [Symptom-based relationship between gastroesophageal reflux disease and laryngopharyngeal reflux disease]. , 2011, Zhonghua yi xue za zhi.

[21]  M. Goutte,et al.  Dilated intercellular space in chronic laryngitis and gastro‐oesophageal reflux disease: at baseline and post‐lansoprazole therapy , 2010, Alimentary pharmacology & therapeutics.

[22]  K. Jung,et al.  An electron microscopic study—Correlation of gastroesophageal reflux disease and laryngopharyngeal reflux , 2010, The Laryngoscope.

[23]  F. J. van der Staay,et al.  The d-amphetamine-treated Göttingen miniature pig: an animal model for assessing behavioral effects of antipsychotics , 2009, Psychopharmacology.

[24]  L. Orlando,et al.  Dilated intercellular spaces as a marker of GERD , 2009, Current gastroenterology reports.

[25]  Liya Zhou,et al.  Dilated intercellular spaces in gastroesophageal reflux disease patients and the changes of intercellular spaces after omeprazole treatment. , 2008, Chinese medical journal.

[26]  J. Dillon,et al.  Prevalence of Laryngopharyngeal Reflux in a Population With Gastroesophageal Reflux , 2007, The Laryngoscope.

[27]  R. Toohill,et al.  Quality of Life in Laryngopharyngeal Reflux Patients , 2007, The Laryngoscope.

[28]  J. Schölmerich,et al.  Self-expanding Polyflex plastic stents in esophageal disease: various indications, complications, and outcomes , 2007, Surgical Endoscopy.

[29]  A. Buda,et al.  Characterisation of adherens and tight junctional molecules in normal animal larynx; determining a suitable model for studying molecular abnormalities in human laryngopharyngeal reflux , 2005, Journal of Clinical Pathology.

[30]  K. Smetana,et al.  The Miniature Pig as an Animal Model in Biomedical Research , 2005, Annals of the New York Academy of Sciences.

[31]  C. Pashos,et al.  The clinical characteristics and impact of laryngopharyngeal reflux disease on health-related quality of life. , 2003, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[32]  J. Koufman,et al.  Laryngopharyngeal Reflux: Position Statement of the Committee on Speech, Voice, and Swallowing Disorders of the American Academy of Otolaryngology-Head and Neck Surgery , 2002, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[33]  R. Knight,et al.  Esophageal Dysmotility As an Important Co‐factor in Extraesophageal Manifestations of Gastroesophageal Reflux , 2000, The Laryngoscope.