The effects of NMDA receptor antagonists over intestinal ischemia/reperfusion injury in rats

Intestinal ischemia/reperfusion causes severe injury and alters motility. N-methyl-D-aspartate (NMDA) receptor antagonists have been shown to reduce ischemia/reperfusion injury in the nervous system, and in other organs. In this study, we set out to investigate the effects of NMDA receptor antagonists over intestinal ischemia/reperfusion injury. Male Wistar rats were randomly divided into four groups: (1) a control, sham-operated group; (2) an intestinal ischemia/reperfusion group subjected to 45 min ischemia and 1h reperfusion; (3) a group treated with 10 mg/kg ketamine before ischemia/reperfusion; and (4) a group treated with 10 mg/kg memantine before ischemia/reperfusion. Intestinal samples were taken for histological evaluation. Serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), malondialdehyde (MDA), total antioxidant capacity, tumor necrosis factor alpha (TNF-alpha), P-selectin and antithrombin III (ATIII) were measured. Intestinal transit time was determined to evaluate intestinal motility. Fecal pellet output and animal weight were also registered daily for 7 days post-ischemia. After reperfusion, AST, LDH, TNF-alpha and P-selectin levels were elevated, ATIII levels were depleted, and ALT levels were unchanged in serum. Additionally, levels of MDA were increased and total antioxidant capacity was reduced in serum, indicating oxidative stress. Intestinal mucosa showed severe injury. Ketamine, but not memantine, diminished these alterations. Intestinal motility and fecal pellet output were also altered after ischemia/reperfusion. Both drugs abolished the alterations in motility. In conclusion, ketamine's protective effects over ischemia/reperfusion do not appear to be NMDA mediated, but they could be playing a role in protecting the intestine against ischemia-induced functional changes.