Characterization of "unhealed gastric ulcers" produced with chronic exposure of acetic acid ulcers to indomethacin in rats.

We previously discovered that a 4-wk course of indomethacin delivered to rats with acetic acid ulcers resulted in production of "unhealed gastric ulcers" that persisted for up to 12 wks after treatment cessation. The present study examined the mechanism underlying such "unhealed gastric ulcers" with biochemical and histological procedures. "Unhealed gastric ulcers" were induced with a 4-wk indomethacin treatment (1 mg/kg, twice daily) in rats with acetic acid ulcers. Two and 4 wks after treatment cessation, ulcer size was significantly larger in rats receiving indomethacin compared with control animals. Ulcerated tissue prostaglandin E2 levels were significantly lower during indomethacin treatment, but the levels tended to increase after treatment cessation compared with levels measure in the group receiving vehicle. Myeloperoxidase activity levels were significantly higher during indomethacin treatment; such levels persisted after treatment cessation. Histologically, greater degrees of fibrosis and neutrophil accumulation, as well as a lesser degree of angiogenesis were observed in the "unhealed gastric ulcers" compared to ulcers that healed in a normal fashion. It was concluded that severe fibrosis, persistent neutrophil infiltration, and poor angiogenesis in the ulcer base might represent factors involved in the mechanism underlying production of "unhealed gastric ulcers".