Document Detail


Detrimental effects of nicotine and endotoxin in the newborn piglet brain during severe hypoxemia.
MedLine Citation:
PMID:  12373070     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hypoxia-ischemia is a major cause of perinatal brain damage, but evidence shows that brain injury also is associated with intrauterine infections and maternal smoking. The mechanisms are not known, and we therefore explored the effects of experimental inflammation or nicotine on perinatal brain metabolism and injury during severe hypoxemia. Twenty-eight 1-week-old piglets were anesthetized and instrumented with microdialysis probes in the striatum and brainstem. We studied three pretreatment groups: (1) 20 microg/kg i.v. nicotine (n = 9); (2) 1 microg/kg i.v. endotoxin from Escherichia coli (n = 11), or (3) control (n = 8). The piglets were subsequently exposed to 30 min of hypoxemia (6% O(2)). In order to minimize any ischemic component and increase survival, this was abrupted for 1 min if blood pressure fell to 30 mm Hg. During hypoxemia, both the pretreatment with endotoxin and nicotine induced higher levels of extracellular lactate and peak lactate/pyruvate ratio compared with controls (54.7 +/- 9.6 (p < 0.01) and 65.2 +/- 13.1 (p < 0.02) vs. 15.9 +/- 7.4, respectively), reflecting a deterioration of the metabolic status in these groups. The two pretreated groups reached significantly higher peak levels of extracellular glycerol (30.9 +/- 4.1 vs. 77.9 +/- 12.7 and 89.4 +/- 14.2 micromol/l, respectively, p = 0.01), indicating a higher level of cellular membrane disintegration or leakage. In addition, 3 endotoxin piglets and 4 nicotine piglets died during reoxygenation, while all controls survived (p = 0.13 and p < 0.04, respectively). Mortality was associated with a rise in extracellular glutamate at the end of hypoxemia/start reoxygenation (p = 0.02). These findings contribute in explaining how nicotine and inflammatory response to bacterial toxins could act as cofactors for hypoxic-ischemic neurologic injury in the immature brain.
Authors:
J Frederik Frøen; Giulia Amerio; Babill Stray-Pedersen; Ola Didrik Saugstad
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biology of the neonate     Volume:  82     ISSN:  0006-3126     ISO Abbreviation:  Biol. Neonate     Publication Date:  2002  
Date Detail:
Created Date:  2002-10-09     Completed Date:  2003-03-13     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0247551     Medline TA:  Biol Neonate     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  188-96     Citation Subset:  IM    
Copyright Information:
Copyright 2002 S. Karger AG, Basel
Affiliation:
Department of Pediatric Research, The National Hospital, University of Oslo, Norway. j.f.froen@klinmed.uio.no
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Newborn*
Anoxia / complications*
Blood Pressure
Brain Diseases / etiology*,  metabolism
Corpus Striatum / metabolism
Endotoxins / administration & dosage,  toxicity*
Escherichia coli
Glutamic Acid / analysis
Glycerol / analysis
Hydrogen-Ion Concentration
Lactic Acid / analysis
Microdialysis
Nicotine / administration & dosage,  toxicity*
Oxygen / administration & dosage
Pyruvic Acid / analysis
Swine
Tumor Necrosis Factor-alpha / analysis,  cerebrospinal fluid
Chemical
Reg. No./Substance:
0/Endotoxins; 0/Tumor Necrosis Factor-alpha; 127-17-3/Pyruvic Acid; 50-21-5/Lactic Acid; 54-11-5/Nicotine; 56-81-5/Glycerol; 56-86-0/Glutamic Acid; 7782-44-7/Oxygen

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


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