DYNAMICS OF DRUG INTERFERENCE WITH HEALING OF EXPERIMENTAL GASTRIC-ULCERS

Objective: We assessed the influence of drugs on ulcer healing dynamic s with a new video endoscopic model. Design: We treated 136 rats with gastric cryo-ulcers with placebo, indomethacin (2 x 0.5 mg/kg subcutan eously), antacid (2 x 1 ml hydrotalcite intragastrically), omeprazole (1 x 40 mumol/kg subcutaneously), indomethacin + omeprazole, indometha cin +antacid or indomethacin alone in different phases of ulcer healin g. The size of the ulcers was determined by video endoscopy (days 1, 3 , 6, 8, 10, 13 and 15) and histologically (days 8 and 15). The speed o f ulcer healing was expressed in terms of the reduction in ulcer diame ter per day. Results: Omeprazole and hydrotalcite significantly accele rated ulcer healing during days 3-8. Indomethacin significantly delaye d healing speed by 1.7- and 4-fold during days 8-10 and 10-15, respect ively. Cotreatment with omeprazole reversed the indomethacin-induced e ffects on ulcer healing to the placebo healing speed. The administrati on of indomethacin on days 1-7 delayed ulcer healing 1.5-fold during d ays 8-13, but had no effect when administered on days 8-14. Conclusion : Drugs predominantly exert their effects in the early healing phase. While acid inhibition accelerates ulcer healing predominantly in the e arly healing phase, the harmful effects of indomethacin on the ulcer h ealing curve become apparent only after a time-lag of 5-7 days.