Gastroenterology

Gastroenterology

Volume 116, Issue 1, January 1999, Pages 97-107
Gastroenterology

Alimentary Tract
Experimental esophagitis induced by acid and pepsin in rabbits mimicking human reflux esophagitis,☆☆

https://doi.org/10.1016/S0016-5085(99)70233-7Get rights and content

Abstract

Background & Aims: The lack of appropriate animal models might explain the paucity of information on the mechanisms of mucosal damage and defense in reflux esophagitis. The aim of this study was to develop a model of esophagitis in rabbits mimicking human reflux esophagitis. Methods: New Zealand white rabbits underwent surgery for placement of a plastic tube into the cervical esophagus. Acidified pepsin (AP) was intermittently perfused for different periods. Esophageal injury was assessed by macroscopic and microscopic examination, including the cell proliferation immunohistochemical parameter mib1. Results: Rabbit losses (20%) were attributable mostly to postsurgical mortality and tube displacement. Perfusion of AP for 60 min/12 h or 45 min/12 h induced high-grade esophagitis by days 3 and 5, respectively, characterized by diffuse erosion/ulceration, inflammation, bleeding, and reactive epithelial changes. Perfusion of acidified pepsin for 60 min/day, especially at 30 min/12 h, induced low-grade esophagitis characterized by superficial epithelial loss, mild/absent inflammation, and epithelial reactive changes including increased cell proliferation, basal hyperplasia, and papillomatosis, which reached maximal expression by day 7. This perfusion regimen induced mucosal adaptation to damage. Conclusions: Different and highly reproducible esophageal mucosal lesions mimicking human reflux esophagitis can be induced in rabbits with repetitive acid and pepsin exposure.

GASTROENTEROLOGY 1999;116:97-107

Section snippets

Materials and methods

All animal studies were carried out in the Service of Biomedicine and Biomaterials of the University of Zaragoza, officially inscribed as a research establishment for the adequate husbandry and use of all research animals under the Good Laboratory Practices norms. New Zealand white rabbits weighing 2.5–3.5 kg each were studied. For surgical procedures, the animals were anesthetized with intramuscular ketamine hydrochloride (75 mg/kg; Parke–Davis, Madrid, Spain) and sodium thiobarbital (5 mm/kg;

Morbidity and mortality

Creation of a cutaneous cervicoesophageal fistula was explored initially but rejected because of extensive loss of food and salivary secretion. Placement of a metallic cannula in the same area was also explored but was not used because of biological rejection. One hundred forty-six rabbits were used with the plastic tubing system described in Materials and Methods; 117 (80%) of them were available for study analysis after completion of perfusions, and 29 (20%) were lost after the surgical

Discussion

To be useful, animal models of human diseases must reproduce, as closely as possible, pathological conditions observed in humans. The lack of appropriate animal models might be one of the reasons for the paucity of information on the mechanisms of damage and defense of the esophageal mucosa. In this study, 2 different and reproducible models of acid- and pepsin-induced chronic esophagitis are reported for the first time in rabbits. Rabbits had been previously used in models of acute esophagitis6

Acknowledgements

The authors thank Dr. E. Salvador for assistance with the perfusion regimen protocols and Sara Serrano and Professor Joaquín Soria for technical assistance with the mib1 studies.

References (21)

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Supported by grants FIS 96/0872 and CYCYT PM-95-0204 from the Fondo de Investigaciones Sanitarias.

☆☆

Address requests for reprints to: Angel Lanas, M.D., Servicio de Aparato Digestivo, Hospital Clínico Universitario, 50009 Zaragoza, Spain. e-mail: [email protected]; fax: (34) 976-76-12-36.

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