Prevention of postischemic injury in immature intestine by deferoxamine

Free radical-mediated reperfusion injury has been demonstrated in ischemic neonatal bowel necrosis, but the mechanism of injury remains elusive. To determine whether such an injury can be prevented, 76 weaning rats were studied to test the effects of deferoxamine, an iron chelator, in postischemic injury. Group I (N = 20) had a sham laparotomy without vascular occlusion. Group II (N = 21) was subjected to 90 min of superior mesenteric artery occlusion prior to reperfusion. Group III (N = 35) received deferoxamine 15 mg/kg intravenous prereperfusion, in addition to ischemia and reperfusion as in group II. Survival profiles for each group were determined and a scale of pathologic severity was applied and compared. Group I had 100% long-term survival and group II, 14%. Group III had an overall survival of 28% and demonstrated a prolonged postreperfusion survival profile (P < 0.002) compared to group II. Histology was nearly identical to human necrotizing enterocolitis in degrees of bowel wall destruction and relative paucity of neutrophils. Group III showed a significant reduction in severity of injury compared to group II (P < 0.003). We conclude that neonatal bowel ischemia conditions such as necrotizing enterocolitis may be reperfusion injuries wherein free iron plays an important role in tissue injury. Administration of an iron chelating agent under such conditions has a beneficial effect on survival and histology.