title: Perflubron emulsion improves hepatic microvascular integrity and mitochondrial redox state after hemorrhagic shock.
abstract: Hemorrhagic shock is associated with decreased systemic oxygen delivery, but also with impaired microvascular perfusion, which can result in diminished local oxygen availability even in the presence of adequate cardiac output after resuscitation. Beside surgical interventions to control blood loss, transfusion of stored packed red blood cells represents the current standard of care in the management of severe hemorrhagic shock. Because stored red blood cells are less deformable and show a higher O2 affinity that affects the O2 off-load to tissues, perfluorocarbon-based artificial oxygen carriers might improve local O2 delivery under these conditions. To test this, rats were subjected to hemorrhagic shock (1 h, mean arterial pressure [MAP] 30-35 mmHg) and were resuscitated with fresh whole blood, pentastarch, stored red blood cells, perflubron emulsion (2.7 and 5.4 g/kg body weight) together with pentastarch, or stored red blood cells together with 2.7 g/kg perflubron emulsion. Hepatic microcirculation, tissue oxygenation, and mitochondrial redox state were investigated by intravital microscopy. In addition, hepatocellular function and liver enzyme release were determined. After hemorrhagic shock and resuscitation with perflubron emulsion, volumetric sinusoidal blood flow was significantly increased compared with resuscitation with stored red blood cells. Furthermore, resuscitation with perflubron emulsion resulted in higher hepatic tissue PO2 and normalized mitochondrial redox potential, which was accompanied by lessened hepatocellular injury as well as improved liver function. These results indicate that, in this model of hemorrhagic shock, asanguineous fluid resuscitation with addition of perflubron emulsion is superior to stored blood or pentastarch alone with respect to increased local O2 availability on the cellular level. This effect is primarily due to improved restoration of hepatic microcirculatory integrity.
authors.affiliation: Department of Biology, University of North Carolina, Charlotte, North Carolina 28223, USA.
authors.forename: Markus
authors.initials: M
authors.lastname: Paxian
authors.forename: Steve A
authors.initials: SA
authors.lastname: Keller
authors.forename: Toan T
authors.initials: TT
authors.lastname: Huynh
authors.forename: Mark G
authors.initials: MG
authors.lastname: Clemens
mesh_terms: D000136:Acid-Base Equilibrium / Q000187:drug effects; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood / Q000187:drug effects; D001783:Blood Flow Velocity / Q000187:drug effects; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D001802:Blood Substitutes / Q000494:pharmacology; D001803:Blood Transfusion; D017707:Erythrocyte Transfusion; D005466:Fluorocarbons / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006400:Hematocrit; D006454:Hemoglobins / Q000032:analysis / Q000187:drug effects; D006842:Hydrocarbons, Brominated; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D006895:Hydroxyethyl Starch Derivatives / Q000494:pharmacology; D007208:Indocyanine Green / Q000493:pharmacokinetics; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000293:injuries; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000503:physiopathology; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009243:NAD / Q000032:analysis / Q000187:drug effects; D009942:Organometallic Compounds / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D010100:Oxygen / Q000032:analysis; D010313:Partial Pressure; D010618:Phenanthrolines / Q000494:pharmacology; D010952:Plasma Substitutes / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation / Q000379:methods; D012771:Shock, Hemorrhagic / Q000503:physiopathology / Q000628:therapy*
chemical_list: D001802:Blood Substitutes; D005466:Fluorocarbons; D006454:Hemoglobins; D006842:Hydrocarbons, Brominated; D006895:Hydroxyethyl Starch Derivatives; D009942:Organometallic Compounds; D010618:Phenanthrolines; D010952:Plasma Substitutes; D009243:NAD; C034282:tris-(1,10-phenanthroline)ruthenium; D001219:Aspartate Aminotransferases; D007208:Indocyanine Green; C003072:perflubron; D010100:Oxygen