title: Effects of Diaspirin Crosslinked Hemoglobin (DCLHb) on microcirculation and local tissue pO2 of striated skin muscle following resuscitation from hemorrhagic shock.
abstract: The hemoglobin based oxygen carrier (HBOC) Diaspirin Crosslinked Hemoglobin (DCLHb) has been developed to substitute not only the blood volume, but also to restore the oxygen-carrying properties of blood during hemorrhagic shock. However, it has been suggested that HBOCs may enhance the formation of free oxygen radicals through the release of free iron ions via the Haber-Weiss reaction. The aim of this study was to investigate the effects of DCLHb on the microcirculation, leukocyte-endothelial cell interaction and local tissue oxygenation in striated skin muscle of Syrian golden hamsters during and after resuscitation from hemorrhagic shock. In particular we focused on the local tissue oxygenation after resuscitation with DCLHb (hemoglobin content 10 g%) compared to resuscitation using autologous blood diluted to a hemoglobin content of 10 g%. Hemorrhagic shock was induced for 45 minutes by bleeding the animals at a rate of 33 ml/kg BW maintaining a mean arterial pressure of 30 +/- 5 mmHg. Animals were resuscitated either with 33 ml/kg BW 6% Dextran-60.000 or with 10 g% DCLHb. The control group received shed blood diluted with Ringers to a hemoglobin content of 10 g%. Intravital microscopy was used for investigation of the microcirculatory parameters and a multiwire platinum surface electrode for measurement of local tissue pO2 in striated skin muscle in the dorsal skinfold chamber of Syrian golden hamsters. Resuscitation from hemorrhagic shock with 10 g% AUB revealed significant increase of leukocytes rolling in postcapillary venules at 30 to 120 minutes after resuscitation compared to baseline values. DCLHb turned out to reduce the number of firmly adherent leukocytes after resuscitation compared to 10 g% AUB. Microvascular permeability as an indicator for functional endothelial integrity revealed no significant differences between the groups. DCLHb and 10 g% AUB led to a significant increase in local tissue oxygenation after resuscitation from hemorrhagic shock. However, 10 g% AUB turned out to be most effective to restore the local tissue pO2 compared to Dx-60. Our findings indicate that DCLHb restores microvascular perfusion after critical hemorrhagic shock as efficient as Dx-60 and 10 g% AUB. The absence of enhanced leukocyte-endothelium interaction after resuscitation with DCLHb implies that this HBOC does not exacerbate formation of oxygen free radicals during reperfusion. DCLHb effectively increases local tissue pO2 after resuscitation from hemorrhagic shock; however, not as effectively as 10 g% AUB.
authors.affiliation: Department for Surgery, Trauma Clinic Murnau, Murnau, Germany. shungerer@bgu-murnau.de
authors.forename: Sven
authors.initials: S
authors.lastname: Hungerer
authors.forename: Dirk
authors.initials: D
authors.lastname: Nolte
authors.forename: Andreas
authors.initials: A
authors.lastname: Botzlar
authors.forename: Konrad
authors.initials: K
authors.lastname: Messmer
mesh_terms: D000818:Animals; D001241:Aspirin / Q000031:analogs & derivatives* / Q000494:pharmacology; D001783:Blood Flow Velocity / Q000187:drug effects; D001802:Blood Substitutes / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D006224:Cricetinae; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006454:Hemoglobins / Q000494:pharmacology* / Q000502:physiology; D007962:Leukocytes / Q000187:drug effects* / Q000502:physiology; D008647:Mesocricetus; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D015424:Reperfusion / Q000379:methods; D012771:Shock, Hemorrhagic / Q000097:blood / Q000188:drug therapy*
chemical_list: D001802:Blood Substitutes; D006454:Hemoglobins; C083478:diaspirin-cross-linked hemoglobin; D001241:Aspirin; D010100:Oxygen