Experimental esophagitis induced by acid and pepsin in rabbits mimicking human reflux esophagitis.
OBJECTIVE
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.
Lanas
A
A
Services of Gastroenterology, Research Unit (Unidad Mixta de Investigación),University Hospital and University of Zaragoza, Spain. alanas@posta.unizar.es
Royo
Y
Y
Ortego
J
J
Molina
M
M
Sáinz
R
R
D000208:Acute Disease; D000818:Animals; D002455:Cell Division; D002908:Chronic Disease; D004195:Disease Models, Animal; D004942:Esophagitis, Peptic / Q000139:chemically induced / Q000473:pathology*; D004947:Esophagus / Q000473:pathology; D006801:Humans; D006851:Hydrochloric Acid / Q000633:toxicity*; D007150:Immunohistochemistry; D009092:Mucous Membrane / Q000473:pathology; D010434:Pepsin A / Q000633:toxicity*; D011817:Rabbits; D013997:Time Factors
D010434:Pepsin A; D006851:Hydrochloric Acid