Natural history and morphology of secretagogue-induced duodenal ulcers in rats

Morphologically typical ulcers were produced in the first part of the duodenum in 300 male Wistar rats by subcutaneous infusion for 24 hr of pentagastrin (4 mug per kg-min) and carbachol (0.8 mug per kg-min). Groups of animals were killed daily for 14 days, and their stomachs and duodenums were examined. Lesions were graded on a seven-point scale: 0, normal; 1, inflammation; 2, petechiae; 3, erosions; 4, definite ulcer crater; 5, penetrating ulcer; and 6, perforated ulcer. Every animal developed one or more definite ulcers (grades 4 to 6). Within the first 48 hr 34% of the animals died with grade 6 ulcers. Ulcer healing began on the 1st postinfusion day when 3 of 46 rats had erosions (grade 3) but no definite ulcer craters. By the following day some animals were found with normal mucosa. After the 5th postinfusion day the few remaining grade 5 or 6 ulcers were those which had perforated and sealed spontaneously. These long-standing ulcers had several features similar to human chronic duodenal ulcers. By the 12th postinfusion day definite ulcers were no longer seen. In this study duodenal ulcers have not only been produced in rats by secretagogues, but have also been observed to heal. This model can be used to compare the efficacy of various antiulcer regimens on ulcer healing.