CHARACTERIZATION OF A SIMPLE ANIMAL-MODEL FOR NONSTEROIDAL ANTIINFLAMMATORY DRUG-INDUCED ANTRAL ULCER

Most animal models of nonsteroidal anti-inflammatory drug (NSAID) indu ced gastric injury are characterized by acute, superficial erosions in the corpus region, whereas the clinically significant injury in man i s the deep, antral ulcer. The purpose of this study was to characteriz e a model of NSAID-induced antral ulceration that more closely resembl es the type of damage seen in man. Rabbits received indomethacin subcu taneously every 12 h. The progression of ulcer formation was followed by killing groups of animals after one to seven doses of indomethacin. The dose dependency of ulcer formation was assessed by giving indomet hacin at doses of 1 to 20 mg/kg. Healing of antral ulcers was determin ed by examining the stomach at various times after administering the s eventh dose of indomethacin (20 mg/kg). The effects of prophylactic tr eatment with misoprostol or ranitidine on ulcer formation were assesse d. Indomethacin administration initially produced superficial erosions in the corpus and antrum, but with time, ulcers became apparent in th e antrum. The formation of these ulcers was dependent upon the number of times indomethacin was administered and the dose. Similar ulcers co uld be induced with a second NSAID, diclofenac. Misoprostol treatment resulted in a significant reduction in the extent of indomethacin-indu ced antral ulceration, but ranitidine had no effect. Antral ulcers hea led progressively following cessation of indomethacin administration a nd were almost completely resolved by 108 h after die final dose of in domethacin. These results demonstrate that subcutaneous NSAID administ ration to rabbits is a simple and reproducible method for producing ul cers that bear striking macroscopic resemblance to NSAID-induced antra l ulcers in man. This model may be useful for studies of the pathogene sis of NSAID-induced ulcer and the factors that modulate the healing o f these ulcers.