Diamine oxidase (DAO; EC 1.4.3.6) is an enzyme found in high activity in the mature cells of the upper villus of rat small intestinal mucosa and in very much lower activity in all other tissues in the nonpregnant rat. This study was designed to determine whether a provocative test for increasing the level of plasma DAO activity by heparin administration could be used to monitor the extent and severity of acute, severe, small intestinal mucosal injury. In adult rats, small intestinal loops of varying lengths were perfused with 2,100 mosM sodium sulfate solution for 60 min to produce selective damage to villus epithelium. Plasma postheparin DAO (PHD) activity (180 min after 400 U/kg i.p. heparin) was measured 7 h after initiation of perfusion. With increasing length of intestinal mucosal injury, there was a progressive decrease in both basal and plasma PHD activity. The decrease in plasma PHD activity closely reflected the length of intestinal mucosa injured (n = 128, r = 0.86, P less than 0.001), and it was much more sensitive (threshold limit of detection = 13% of total length, range = 67 U/ml for 100% length of injury) than unstimulated basal levels of plasma DAO (threshold = 40%, range = 2.1 U/ml). Our previous data have suggested that DAO is unique among intestinal mucosal enzymes in that circulating levels can serve as a marker of mucosal injury; this study illustrates that the addition of a low-dose heparin administration enhances the use of DAO even further as a sensitive, quantitative, circulating marker for monitoring the extent of small intestinal mucosal injury in the rat.
G D Luk, T M Bayless, S B Baylin