Perflubron emulsion in prolonged hemorrhagic shock: influence on hepatocellular energy metabolism and oxygen-dependent gene expression.
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.
Paxian
Markus
M
Klinik für Anaesthesiologie und Intensivmedizin, Universität des Saarlandes, Hamburg, Germany.
Rensing
Hauke
H
Geckeis
Katrin
K
Bauer
Inge
I
Kubulus
Darius
D
Spahn
Donat R
DR
Bauer
Michael
M
D000136:Acid-Base Equilibrium / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001802:Blood Substitutes / Q000008:administration & dosage / Q000627:therapeutic use*; D015153:Blotting, Western; D004655:Emulsions; D004734:Energy Metabolism / Q000187:drug effects*; D005466:Fluorocarbons / Q000008:administration & dosage / Q000627:therapeutic use*; D015870:Gene Expression / Q000187:drug effects*; D005974:Glutamate-Ammonia Ligase / Q000096:biosynthesis / Q000235:genetics; D006400:Hematocrit; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D006842:Hydrocarbons, Brominated; D006895:Hydroxyethyl Starch Derivatives / Q000627:therapeutic use; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008102:Liver Circulation / Q000187:drug effects; D008297:Male; D010100:Oxygen / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000188:drug therapy*
D001802:Blood Substitutes; D004655:Emulsions; D005466:Fluorocarbons; D006842:Hydrocarbons, Brominated; D006895:Hydroxyethyl Starch Derivatives; D000255:Adenosine Triphosphate; D005974:Glutamate-Ammonia Ligase; C003072:perflubron; D010100:Oxygen