Document Detail


Endotoxin-induced ileal mucosal hyperpermeability in pigs: role of tissue acidosis.
MedLine Citation:
PMID:  7513959     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Administration of lipopolysaccharide (LPS) to experimental animals leads to diminished mesenteric perfusion, increased ileal mucosal [H+] , and increased gut epithelial permeability to hydrophilic solutes. We sought to determine whether these phenomena are causally related. Experiments were performed in anesthetized pigs. Permeability was assessed by measuring the plasma-to-lumen clearance of fluorescein isothiocyanate dextran (4,000 Da; FD-4) by a segment of ileum perfused with Ringer lactate solution. Mucosal perfusion (Qmuc) and [H4+] were estimated using laser-Doppler flowmetry and tonometry, respectively. In an initial series of experiments, we showed that mucosal permeability was linearly correlated with mucosal [H+] in animals subjected to graded degrees of mechanically induced mesenteric ischemia (n = 14, R2 = 0.58, P < 0.002) or injected with graded doses of LPS (n = 11, R2 = 0.93, P < 0.0001). In a second series of experiments, we induced mucosal acidosis in normal pigs by mechanical ventilation with either a hypoxic (n = 7) or a hypercapnic (n = 5) gas mixture. In both groups, ileal mucosal permeability to FD-4 increased significantly (P < 0.05), although transmesenteric release of lactate increased significantly only in the hypoxic group. Qmuc was unchanged in both groups. These data suggest that mucosal acidosis, even in the absence of tissue ischemia or hypoxia, increases intestinal permeability to a macromolecular hydrophilic solute. Tissue acidosis may be an important factor contributing to LPS-induced gut mucosal hyperpermeability.
Authors:
A L Salzman; H Wang; P S Wollert; T J Vandermeer; C C Compton; A G Denenberg; M P Fink
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The American journal of physiology     Volume:  266     ISSN:  0002-9513     ISO Abbreviation:  Am. J. Physiol.     Publication Date:  1994 Apr 
Date Detail:
Created Date:  1994-06-09     Completed Date:  1994-06-09     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0370511     Medline TA:  Am J Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  G633-46     Citation Subset:  IM    
Affiliation:
Department of Surgery, Massachusetts General Hospital, Boston 02114.
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MeSH Terms
Descriptor/Qualifier:
Acidosis / metabolism*
Animals
Arteries
Dextrans
Endotoxins / pharmacology*
Fluorescein-5-isothiocyanate / analogs & derivatives
Gases / blood
Hemodynamics / drug effects
Hydrogen / blood
Ileum / metabolism*
Intestinal Mucosa / metabolism*
Lactates / blood
Lactic Acid
Male
Osmolar Concentration
Oxygen / blood
Permeability / drug effects
Splanchnic Circulation
Swine
Veins
Grant Support
ID/Acronym/Agency:
2-R01-GM-37631-07/GM/NIGMS NIH HHS; 5-T32-GM-07035/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Endotoxins; 0/Gases; 0/Lactates; 0/fluorescein isothiocyanate dextran; 1333-74-0/Hydrogen; 3326-32-7/Fluorescein-5-isothiocyanate; 50-21-5/Lactic Acid; 7782-44-7/Oxygen; 9004-54-0/Dextrans

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