Background
The gut is a target organ of shock/resuscitation (S/R); however, it also contributes
to distant inflammation through the generation of oxidants. S/R with antioxidants
such as N-acetylcysteine (NAC) prevents lipopolysaccharide (LPS)-induced cytokine
production and NF-κB activation in rat alveolar macrophages. Therefore, we hypothesized
that hypertonic saline (HTS) might exerts its protective effect by preventing gut
ischemia/reperfusion injury, thus decreasing oxidative stress and distant priming
in alveolar macrophages.
Methods
A two-hit rat model of shock resuscitation was used. Plasma levels of 8-iso-prostaglandin,
a marker of lipid peroxidation, was quantified by eicosanoid immunoassay with acetylcholinesterase
kit. Gut histology with hematoxylin and eosin staining was performed 1 to 6 hours
after resuscitation. Alternatively, alveolar macrophages from bronchoalveolar lavage
(BAL) at end resuscitation were incubated in vitro with LPS (0.01 μg/mL), and NF-κB
translocation was observed by immunofluorescent staining with anti-p65 antibody.
Results
HTS resuscitation prevented leukosequestration in the alveolar space, and it abrogated
the progressive rise in blood 8-iso-prostaglandin production observed with Ringer's
lactate (RL) resuscitation. Inhibition of oxidant stress with NAC corresponded with
the ability of HTS to prevent S/R-induced edema, villus flattening, and mucosal sloughing
in the mid-ileum. LPS-induced NF-κB translocation in alveolar macrophages after RL
was 42% compared to 20% after HTS. Similar attenuation was observed with NAC resuscitation
(16%).
Conclusions
HTS resuscitation prevents systemic oxidative stress by reducing gut ischemia/reperfusion
injury and consequently attenuates distant alveolar macrophage priming, thereby reducing
LPS-induced NF-κB nuclear translocation in alveolar macrophages and organ injury.
This represents a novel mechanism whereby HTS exerts its immunomodulatory effects.
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Article info
Publication history
Toronto, Canada
Footnotes
Presented at the 65th Annual Meeting of the Society of University Surgeons, St. Louis, Missouri, February 11-14, 2004.
Supported by the Canadian Institutes of Health Research and the Canadian Infectious Disease Society. Dr Powers is a recipient of the American College of Surgeons Wyeth Pharmaceuticals Scholarship. Dr Khadaroo is supported by the Alberta Heritage Foundation. Drs Kapus and Szaszi are recipients of support awards from the Canadian Institutes of Health Research.
Identification
Copyright
© 2005 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
