Experimental esophagitis induced by acid and pepsin in rabbits mimicking human reflux esophagitis  Angel Lanas*, Yolanda Royo‡, Javier Ortego§, M. Molina*, R. Sáinz*  Gastroenterology  Volume 116, Issue 1, Pages 97-107 (January 1999) DOI: 10.1016/S0016-5085(99)70233-7 Copyright © 1999 American Gastroenterological Association Terms and Conditions

Fig. 1 Surgical procedure used to perfuse AP into the esophageal lumen. Rabbits underwent surgery for placement of a plastic tube (internal diameter, 5 mm) into the lumen of the cervical esophagus. The tube was secured with surgical ligatures, tunneled, and fixed through the skin on the posterior cervical area, allowing free access to the lumen of the esophagus. Gastroenterology 1999 116, 97-107DOI: (10.1016/S0016-5085(99)70233-7) Copyright © 1999 American Gastroenterological Association Terms and Conditions

Fig. 2 Microphotograph of immunohistochemical staining with the antibody mib1, which detects the Ki67 nuclear antigen of proliferation, showing more than 5 rows of proliferating cells at the basal level. Gastroenterology 1999 116, 97-107DOI: (10.1016/S0016-5085(99)70233-7) Copyright © 1999 American Gastroenterological Association Terms and Conditions

Fig. 3 Macroscopic and microscopic scores of mucosal damage with the different perfusion regimens of 60, 45, and 30 minutes at days (A) 3 and (B) 5 (**P < 0.001 vs. other regimens; *P < 0.05 vs. 30 min/12 h). Gastroenterology 1999 116, 97-107DOI: (10.1016/S0016-5085(99)70233-7) Copyright © 1999 American Gastroenterological Association Terms and Conditions

Fig. 3 Macroscopic and microscopic scores of mucosal damage with the different perfusion regimens of 60, 45, and 30 minutes at days (A) 3 and (B) 5 (**P < 0.001 vs. other regimens; *P < 0.05 vs. 30 min/12 h). Gastroenterology 1999 116, 97-107DOI: (10.1016/S0016-5085(99)70233-7) Copyright © 1999 American Gastroenterological Association Terms and Conditions

Fig. 4 Macroscopic and microscopic scores of mucosal damage with the different perfusion regimens (60, 45, and 30 minutes) at different time intervals. (A) **P ≤ 0.01 vs. all others; φP < 0.05 vs. all microscopic scores and macroscopic scores of the 60 min/12 h regimen. (B) **P < 0.01, *P < 0.05 vs. day 1. (C) **P < 0.01, *P < 0.05 vs. days 1, 5, 7, and 20. Gastroenterology 1999 116, 97-107DOI: (10.1016/S0016-5085(99)70233-7) Copyright © 1999 American Gastroenterological Association Terms and Conditions

Fig. 4 Macroscopic and microscopic scores of mucosal damage with the different perfusion regimens (60, 45, and 30 minutes) at different time intervals. (A) **P ≤ 0.01 vs. all others; φP < 0.05 vs. all microscopic scores and macroscopic scores of the 60 min/12 h regimen. (B) **P < 0.01, *P < 0.05 vs. day 1. (C) **P < 0.01, *P < 0.05 vs. days 1, 5, 7, and 20. Gastroenterology 1999 116, 97-107DOI: (10.1016/S0016-5085(99)70233-7) Copyright © 1999 American Gastroenterological Association Terms and Conditions

Fig. 4 Macroscopic and microscopic scores of mucosal damage with the different perfusion regimens (60, 45, and 30 minutes) at different time intervals. (A) **P ≤ 0.01 vs. all others; φP < 0.05 vs. all microscopic scores and macroscopic scores of the 60 min/12 h regimen. (B) **P < 0.01, *P < 0.05 vs. day 1. (C) **P < 0.01, *P < 0.05 vs. days 1, 5, 7, and 20. Gastroenterology 1999 116, 97-107DOI: (10.1016/S0016-5085(99)70233-7) Copyright © 1999 American Gastroenterological Association Terms and Conditions

Fig. 5 Microphotographs of mild esophageal damage (low-grade esophagitis) obtained after perfusion of AP for 30 min/12 h for 7 days (H&E stain). (A) Superficial epithelial loss, basal hyperplasia, and extended papillae. (B) Extended papillae, basal hyperplasia, vasodilatation, and edema of the submucosa. Gastroenterology 1999 116, 97-107DOI: (10.1016/S0016-5085(99)70233-7) Copyright © 1999 American Gastroenterological Association Terms and Conditions

Fig. 6 Macroscopic appearance of formaldehyde-fixed esophageal specimens. (A) Mild esophagitis showing edema, hyperemia, petechia, and focal and isolated areas of submucosal hemorrhage. (B) Severe esophagitis with extensive longitudinal erosion, ulceration, and bleeding of the lower and middle esophagus. (C) Severe esophageal damage with longitudinal and confluent ulceration of the middle esophagus. Gastroenterology 1999 116, 97-107DOI: (10.1016/S0016-5085(99)70233-7) Copyright © 1999 American Gastroenterological Association Terms and Conditions

Fig. 7 Microphotographs of severe esophageal damage (high-grade esophagitis) obtained after perfusion of AP for 45 min/12 h for 5 days (H&E stain). (A) Extensive epithelial loss with intense edema and infiltration of inflammatory cells (polymorphonuclear and lymphocyte) in the mucosa and submucosa. (B) Details of specimens with ulceration and moderate infiltration of inflammatory cells. (C) Other areas with extended papillae, edema, and bleeding. Gastroenterology 1999 116, 97-107DOI: (10.1016/S0016-5085(99)70233-7) Copyright © 1999 American Gastroenterological Association Terms and Conditions