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Seven or fourteen days or twelve months after suturing one tube into the pyloric sphincter (removed by peristalsis by the seventh day), rats exhibit prolonged esophagitis with a constantly lowered pressure not only in the pyloric, but also in the lower esophageal sphincter and a failure of both sphincters. Throughout the esophagitis experiment, gastric pentadecapeptide BPC 157 (PL 14736) is given intraperitoneally once a day (10 µg/kg, 10 ng/kg, last application 24 h before assessment), or continuously in drinking water at 0.16 µg/ml, 0.16 ng/ml (12 ml/rat per day), or directly into the stomach 5 min before pressure assessment (a water manometer connected to the drainage port of a Foley catheter implanted into the stomach either through an esophageal or duodenal incision). This treatment alleviates i) the esophagitis (macroscopically and microscopically, at either region or interval), ii) the pressure in the pyloric sphincter, and iii) the pressure in the lower esophageal sphincter (cmH2O). In the normal rats it increases lower esophageal sphincter pressure, but decreases the pyloric sphincter pressure. Ranitidine, given using the same protocol (50 mg/kg, intraperitoneally, once daily; 0.83 mg/ml in drinking water; 50 mg/kg directly into the stomach) does not have an effect in either rats with esophagitis or in normal rats.

We report a simple novel rat model that combines prolonged esophagitis and parallel sphincters failure. The anti-ulcer gastric pentadecapeptide BPC 157, which was found to be stable in gastric juice, and is being evaluated in inflammatory bowel disease trials, is an antiesophagitis therapy that recovers failed sphincters. Twelve or twenty months after the initial challenge (tubes sutured into sphincters for one week and then spontaneously removed by peristalsis), rats exhibit prolonged esophagitis (confluent hemorrhagic and yellowish lesions, thinner epithelium and superficial corneal layer, with stratification derangement); constantly lowered pressure of both sphincters (assessed by using a water manometer connected to the drainage port of a Foley catheter implanted into the stomach either through esophageal or duodenal incision); and both lower esophageal and pyloric sphincter failure. Throughout the esophagitis experiment, BPC 157 was given at either 10 µg/kg, i.p., once a day (last application 24 h before assessment) or alternatively, it was given continuously in drinking water at 0.16 µg/ml (12 ml/rat). This treatment recovers i) esophagitis (macroscopically and microscopically, at either region or investigated time period) and ii) pressure in both sphincters (cmH2O). In addition, BPC 157 (10 µg/kg) or saline (1 ml/rat, 5 ml/kg) was specifically given directly into the stomach; pressure assessment was performed at 5 min thereafter. The effect of BPC 157 is specific because in normal rats, it increases lower esophageal sphincter-pressure, but decreases pyloric sphincter-pressure. Ranitidine, given as the standard drug using the same protocol (50 mg/kg, i.p., once daily; 0.83 mg/ml in drinking water; or 50 mg/kg directly into the stomach) had no effect.