Document Detail


Hypercapnia via reduced rate and tidal volume contributes to lipopolysaccharide-induced lung injury.
MedLine Citation:
PMID:  15477499     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Appreciating that CO2 modifies the chemical reactivity of nitric oxide (NO)-derived inflammatory oxidants, we investigated whether hypercapnia would modulate pulmonary inflammatory responses. Rabbits (n = 72) were ventilated with approximately 7-ml/kg tidal volume for 6 hours. Animals were randomized to one of the following conditions: eucapnia (Pa(CO2) at approximately 35-40 mm Hg), eucapnia + lipopolysaccharide (LPS), eucapnia + LPS + inhaled NO (iNO delivered at approximately 20 ppm), hypercapnia (Pa(CO2) at approximately 60 mm Hg), hypercapnia + LPS, and hypercapnia + LPS + iNO. The hypercapnia + LPS groups compared with groups exposed to eucapnia + LPS displayed significantly increased bronchoalveolar lavage fluid protein concentrations (p < 0.05), lung wet-to-dry ratios (p < 0.05), bronchoalveolar lavage fluid cell counts (p < 0.05), and lung histologic alterations consistent with greater injury. Furthermore, expression of inducible nitric oxide synthase (p < 0.05), tissue myeloperoxidase content (p < 0.05), and formation of lung protein 3-nitrotyrosine derivatives (p < 0.05) was greatest under conditions of hypercapnia + LPS. Groups exposed to hypercapnic conditions without LPS did not manifest these changes. The inhalation of iNO attenuated selected indices of lung injury. We conclude that hypercapnia induced by means of reduced rate and tidal volume amplifies pulmonary inflammatory responses.
Authors:
John D Lang; Mario Figueroa; K David Sanders; Mutay Aslan; Yuliang Liu; Phillip Chumley; Bruce A Freeman
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Publication Detail:
Type:  Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2004-10-11
Journal Detail:
Title:  American journal of respiratory and critical care medicine     Volume:  171     ISSN:  1073-449X     ISO Abbreviation:  Am. J. Respir. Crit. Care Med.     Publication Date:  2005 Jan 
Date Detail:
Created Date:  2005-01-10     Completed Date:  2005-02-15     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9421642     Medline TA:  Am J Respir Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  147-57     Citation Subset:  AIM; IM    
Affiliation:
Department of Anesthesiology, The University of Alabama at Birmingham, Birmingham, Alabama 35233-6810, USA. john.lang@ccc.uab.edu
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Animals
Carbon Dioxide / adverse effects,  blood,  therapeutic use
Hypercapnia / pathology,  physiopathology*
Immunohistochemistry
Inflammation / physiopathology
Lipopolysaccharides
Nitric Oxide / adverse effects,  blood,  therapeutic use
Rabbits
Random Allocation
Respiration, Artificial / methods*
Respiratory Distress Syndrome, Adult / pathology,  physiopathology*,  therapy*
Tidal Volume
Grant Support
ID/Acronym/Agency:
KO8 HL67982/HL/NHLBI NIH HHS; R01 HL58115/HL/NHLBI NIH HHS; R01 HL58115-6/HL/NHLBI NIH HHS; R01 HL64937/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Lipopolysaccharides; 10102-43-9/Nitric Oxide; 124-38-9/Carbon Dioxide
Comments/Corrections
Comment In:
Am J Respir Crit Care Med. 2005 Jan 15;171(2):96-7   [PMID:  15640370 ]

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


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