Experimental esophagitis induced by acid and pepsin in rabbits mimicking human reflux esophagitis

Background & Aims: The lack of appropriate animal models might explain the paucity of information on the mechanisms of mucosal damage and defense in r eflux esophagitis. The aim of this study was to develop a model of esophagi tis in rabbits mimicking human reflux esophagitis. Methods: New Zealand whi te rabbits underwent surgery for placement of a plastic tube into the cervi cal esophagus. Acidified pepsin (AP) was intermittently perfused for differ ent 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 postsurgica l mortality and tube displacement. Perfusion of AP for 60 min/12 h or 45 mi n/12 h induced high-grade esophagitis by days 3 and 5, respectively, charac terized by diffuse erosion/ulceration, inflammation, bleeding, and reactive epithelial changes. Perfusion of acidified pepsin for 60 min/day, especial ly at 30 min/12 h, induced low-grade esophagitis characterized by superfici al epithelial loss, mild/absent inflammation, and epithelial reactive chang es including increased cell proliferation, basal hyperplasia, and papilloma tosis, which reached maximal expression by day 7. This perfusion regimen in duced mucosal adaptation to damage. Conclusions: Different and highly repro ducible esophageal mucosal lesions mimicking human reflux esophagitis can b e induced in rabbits with repetitive acid and pepsin exposure.