Document Detail


Effects of N-acetylcysteine on intestinal reoxygenation injury in hypoxic newborn piglets resuscitated with 100% oxygen.
MedLine Citation:
PMID:  19332996     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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. OBJECTIVES: 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:
Scott T Johnson; David L Bigam; Marwan Emara; Graham Slack; Laurence D Jewell; Laila Obaid; Gregory Korbutt; John Van Aerde; Po-Yin Cheung
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-03-31
Journal Detail:
Title:  Neonatology     Volume:  96     ISSN:  1661-7819     ISO Abbreviation:  Neonatology     Publication Date:  2009  
Date Detail:
Created Date:  2009-09-24     Completed Date:  2010-01-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101286577     Medline TA:  Neonatology     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  162-70     Citation Subset:  IM    
Copyright Information:
Copyright 2009 S. Karger AG, Basel.
Affiliation:
Department of Surgery, University of Alberta, Edmonton, Alta., Canada.
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MeSH Terms
Descriptor/Qualifier:
Acetylcysteine / therapeutic use*
Animals
Animals, Newborn
Anoxia / complications,  drug therapy*,  metabolism
Antioxidants / therapeutic use*
Disease Models, Animal
Enterocolitis / drug therapy*,  metabolism,  pathology
Ileum / drug effects,  pathology
Oxygen / adverse effects*
Oxygen Inhalation Therapy
Reperfusion Injury / drug therapy*,  metabolism,  pathology
Splanchnic Circulation / drug effects
Swine
Chemical
Reg. No./Substance:
0/Antioxidants; 616-91-1/Acetylcysteine; 7782-44-7/Oxygen

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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