title: Effects of N-acetylcysteine on intestinal reoxygenation injury in hypoxic newborn piglets resuscitated with 100% oxygen.
abstract: BACKGROUND
  Neonatal asphyxia may lead to the development of ischemia-reperfusion induced intestinal injury, which is related to oxygen-derived free radical production. N-Acetylcysteine (NAC) is a thiol-containing antioxidant which increases intracellular stores of glutathione.
  
  
  OBJECTIVE
  Using a swine model of neonatal hypoxia-reoxygenation, we examined whether administration of NAC after resuscitation improved intestinal perfusion and reduced intestinal damage.
  
  
  METHODS
  Twenty-four piglets (1-4 days old, 1.4-2.2 kg) were anesthetized and acutely instrumented for continuous monitoring of superior mesenteric arterial flow and oxygen delivery. Alveolar hypoxia was induced for 2 h, followed by resuscitation with 100% oxygen for 1 h and 21% oxygen for 3 h. Animals were randomized to sham-operated, hypoxic control and NAC treatment (150 mg/kg i.v. at 0 or 10 min of reoxygenation followed by infusion 100 mg/kg/h) groups. During hypoxia-reoxygenation, intestinal tissue glutathione content, caspase-3 activity and reoxygenation injury were examined.
  
  
  RESULTS
  After 2 h of hypoxia, piglets were acidotic and hypotensive, with significantly depressed blood flow and oxygen delivery to the small intestine. Upon reoxygenation, hemodynamics recovered as did oxygen supply to the small intestine. After 4 h of reoxygenation, the NAC treatment improved mesenteric flow and oxygen delivery. Despite reducing the increase in caspase-3 activities after hypoxia-reoxygenation by NAC treatment, no significant differences in the glutathione content and histological grading of ileal injury were found among the experimental groups.
  
  
  CONCLUSIONS
  In newborn piglets with hypoxia-reoxygenation, NAC may improve mesenteric blood flow and oxygen delivery without significant effect on tissue glutathione content. The protective role of NAC in the reoxygenated intestine after severe hypoxia warrants further investigation.
authors.affiliation: Department of Surgery, University of Alberta, Edmonton, Alta., Canada.
authors.forename: Scott T
authors.initials: ST
authors.lastname: Johnson
authors.forename: David L
authors.initials: DL
authors.lastname: Bigam
authors.forename: Marwan
authors.initials: M
authors.lastname: Emara
authors.forename: Graham
authors.initials: G
authors.lastname: Slack
authors.forename: Laurence D
authors.initials: LD
authors.lastname: Jewell
authors.forename: Laila
authors.initials: L
authors.lastname: Obaid
authors.forename: Gregory
authors.initials: G
authors.lastname: Korbutt
authors.forename: John
authors.initials: J
authors.lastname: Van Aerde
authors.forename: Po-Yin
authors.initials: PY
authors.lastname: Cheung