DIFFERENTIAL EFFECT OF INDOMETHACIN AND KETOROLAC ON POSTOPERATIVE ILEUS IN RATS

The effect of two prostaglandin biosynthesis inhibitors and their inte raction with the L-arginine/nitric oxide (NO) pathway was investigated in a rat model of experimental ileus. The gastrointestinal transit wa s measured as the migration of Evans blue after three different operat ions. Indomethacin completely reversed the additional inhibition of th e transit induced by mechanical stimulation of the gut. Ketorolac comp letely reversed the inhibition of the transit induced by the laparotom y, but had no additional effect on the inhibition induced by mechanica l stimulation of the gut. Administration of indomethacin plus L-nitroa rginine or L-arginine could not enhance or prevent the effect of indom ethacin alone. Administration of ketorolac and L-nitroarginine complet ely reversed the transit after the laparotomy plus manipulation wherea s ketorolac plus L-arginine had no additional effect as compared to ke torolac alone. From these findings we conclude that in addition to NO, prostaglandins are involved in the pathogenesis of postoperative ileu s in the rat. However, indomethacin and ketorolac differentially affec t postoperative ileus suggesting that prostaglandins an involved in di fferent pathogenic mechanisms leading to postoperative ileus. (C) 1998 Elsevier Science B.V.