INDOMETHACIN DAMAGE TO RAT GASTRIC-MUCOSA IS MARKEDLY DEPENDENT ON LUMINAL PH

1. There is good evidence that acid is a prerequisite for aspirin indu ced gastric mucosal damage; however, there is inconsistent information available for non-salicylate NSAID, The present study examines the ef fect of gastric luminal pH on indomethacin-induced gastric mucosal dam age. 2. Macroscopic gastric mucosal damage induced by indomethacin (40 mg/kg) or vehicle, administered intraduodenally to male pylorus-ligat ed rats (n = 5-10/group), was assessed at four different levels of lum inal pH (2,4,5.5 and 7) by means of digital planimetry. 3. There was a marked difference in the extent of damage induced by indomethacin at the different luminal pH levels (P = 0.001), There was no difference b etween the percentage of haemorrhagic lesions at pH 2 and 4 (P > 0.05) , nor between pH 5.5 and 7 (P > 0.05), However, the damage at the high levels of luminal acidity (pH 2 and 4) was strikingly different from that at pH 5.5 and 7 (P < 0.05). 4. Gastric mucosal damage induced by indomethacin, a non-salicylate NSAID, is augmented by the presence of high concentrations of acid in the gastric lumen, The main finding, th at indomethacin injury is markedly less above pH 4, may have clinical implications in the prevention of NSAID-induced mucosal injury.