THE ROLE OF TRANSIENT MUCOSAL ISCHEMIA IN ACETIC ACID-INDUCED COLITISIN THE RAT

The importance of early microcirculatory changes in the rat colon afte r exposure to acetic acid was investigated. Administration of 4% aceti c acid for 15 sec into an exteriorized colonic segment induced a marke d, transient (starting 2 min after the challenge with acetic acid and persisting for 15 min) decrease in the colonic blood flow as estimated by a laser-Doppler flowmeter. Four days after acetic acid administrat ion, a uniform colitis had developed in the exteriorized colonic segme nt with a total morphological score (TMS) of 15.1 +/- 0.8, myeloperoxi dase activity (MPO) increased more than threefold, and plasma exudatio n into the colonic lumen increased sevenfold. Administration of hydroc hloric acid (HCl) with the same pH as the acetic acid or sodium acetat e (pH 7.0) did not affect colonic blood flow or produce colitis. Mecha nical colonic ischemia, induced by a controlled increase in the intral uminal pressure, resulted in several pathological features of colitis with a TMS of 7.3 +/- 0.2, combined with a significant increase in MPO activity. The TMS and MPO were further increased when mechanical colo nic ischemia was combined with HCl or sodium acetate. Pretreatment wit h SOD and catalase 5 or 15 min before acetic acid administration did n ot affect the transient ischemia immediately following acetic acid adm inistration. However, it partially prevented the development of coliti s. It is concluded that immediate transient ischemia accompanied by th e generation of oxygen free radicals might be of importance in the pat hogenesis of acetic acid-induced colitis in the rat. (C) 1996 Academic Press, Inc.