Document Detail


Perflubron emulsion in prolonged hemorrhagic shock: influence on hepatocellular energy metabolism and oxygen-dependent gene expression.
MedLine Citation:
PMID:  12766648     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Liver dysfunction as a result of impaired oxygen availability frequently occurs following hemorrhage and contributes to delayed mortality. Artificial oxygen carriers may improve oxygen supply to vital organs while avoiding the need for allogeneic transfusion. METHODS: Rats were subjected to hemorrhagic hypotension (mean arterial pressure = 35-40 mmHg for 120 min) and were subsequently resuscitated with (1) stored whole rat blood, (2) pentastarch, or (3) pentastarch combined with perflubron emulsion (PFE; 2.7 or 5.4 g/kg body weight), a second-generation artificial oxygen carrier. Recovery of liver adenosine triphosphate, hepatocellular injury, and expression of glutamine synthetase 1, a gene that is induced by exposure of hepatocytes to low partial pressure of oxygen, were studied at 4 h of resuscitation. RESULTS: Stored whole blood or pentastarch failed to restore liver adenosine triphosphate concentrations after prolonged shock as compared to sham controls and resulted in increased gene expression of glutamine synthetase 1. Addition of 2.7 g PFE/kg restored liver adenosine triphosphate to control, whereas 5.4 g PFE/kg resulted in adenosine triphosphate concentrations significantly above control. Improved hepatocellular oxygen supply was also confirmed by restoration of the physiologic expression pattern of glutamine synthetase 1. Serum enzyme concentrations were highest after resuscitation with stored blood, whereas addition of PFE failed to further decrease enzyme concentrations as compared to pentastarch alone. CONCLUSIONS: Resuscitation with PFE is superior to stored blood or asanguineous resuscitation with respect to restoration of hepatocellular energy metabolism. The improved hepatocellular oxygen availability is reflected in normalization of oxygen-dependent gene expression. However, improved oxygen availability failed to affect early hepatocellular injury.
Authors:
Markus Paxian; Hauke Rensing; Katrin Geckeis; Inge Bauer; Darius Kubulus; Donat R Spahn; Michael Bauer
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anesthesiology     Volume:  98     ISSN:  0003-3022     ISO Abbreviation:  Anesthesiology     Publication Date:  2003 Jun 
Date Detail:
Created Date:  2003-05-26     Completed Date:  2003-06-24     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1300217     Medline TA:  Anesthesiology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1391-9     Citation Subset:  AIM; IM    
Affiliation:
Klinik für Anaesthesiologie und Intensivmedizin, Universität des Saarlandes, Hamburg, Germany.
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MeSH Terms
Descriptor/Qualifier:
Acid-Base Equilibrium / drug effects
Adenosine Triphosphate / metabolism
Animals
Blood Substitutes / administration & dosage,  therapeutic use*
Blotting, Western
Emulsions
Energy Metabolism / drug effects*
Fluorocarbons / administration & dosage,  therapeutic use*
Gene Expression / drug effects*
Glutamate-Ammonia Ligase / biosynthesis,  genetics
Hematocrit
Hepatocytes / drug effects,  enzymology,  metabolism*
Hetastarch / therapeutic use
Immunohistochemistry
Liver / drug effects,  enzymology,  metabolism*
Liver Circulation / drug effects
Male
Oxygen / physiology*
Rats
Rats, Sprague-Dawley
Resuscitation
Shock, Hemorrhagic / drug therapy*
Chemical
Reg. No./Substance:
0/Blood Substitutes; 0/Emulsions; 0/Fluorocarbons; 423-55-2/perflubron; 56-65-5/Adenosine Triphosphate; 7782-44-7/Oxygen; 9005-27-0/Hetastarch; EC 6.3.1.2/Glutamate-Ammonia Ligase

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


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