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Necrotizing enterocolitis (NEC) is an intestinal disease with significant morbidity and mortality in the newborn infant. Animal models of NEC implicate hypoxia and hypothermia in causing ischemic intestinal injury. The pathogenesis of intestinal injury in low flow states may be mediated by O2 radicals. We hypothesized O2 radicals generated by the xanthine dehydrogenase (XD)/xanthine oxidase (XO) system augment injury and an XO inhibitor, allopurinol (AP) would decrease injury.
We exposed 1-2 day old piglets to 30 minutes of hypoxia and hypothermia under isoflurane anesthesia. Piglets were assigned to these groups (n=4): 1) control: hypoxia/hypothermia only 2) AP: 35mg/kg q 12h beginning 24h prior to hypoxia/hypothermia. Hypoxia was achieved by hypoventilation with room air to maintain pO2 at 40 mm Hg. Hypothermia was achieved by removing heat sources and maintaining temperature at 4°C below normal core temperature. Piglets were then recovered. After nursing for 48 hours, animals were sacrificed and intestinal tracts removed. Sections of proximal (PSB), mid(MSB), distal small bowel (DSB), proximal (PC), and distal colon (DC) were examined histologically by a pathologist using a standard scale (0-4) for ischemic intestinal injury. Results are median values. Table
Ozolek, J., Cassutto, B., Argyle, J. et al. Effect of Allopurinol on Hypoxic/Ischemic Intestinal Injury in the Neonatal Piglet † 1087.
Pediatr Res43
(Suppl 4), 187 (1998). https://doi.org/10.1203/00006450-199804001-01108