title: Effects of recombinant-hemoglobin solutions rHb2.0 and rHb1.1 on blood pressure, intestinal blood flow, and gut oxygenation in a rat model of hemorrhagic shock.
abstract: The vasoconstriction induced by hemoglobin-based oxygen carriers (HBOCs), mainly a result of nitric oxide (NO) scavenging, until now has limited the application of HBOCs as resuscitation fluids. In this study, we tested the hypothesis that the new modified recombinant-hemoglobin solution rHb2.0, with a 20 to 30 times lesser NO-scavenging rate, would minimize vasoconstriction without adverse effects on microvascular oxygenation. Responses were compared with those to rHb1.1, a recombinant-hemoglobin solution with a wild-type NO-scavenging rate, as well as an oncotically matched albumin solution. In a fixed-pressure (40 mm Hg) rat model of hemorrhagic shock and resuscitation, rHb2.0 and albumin both restored mean arterial pressure (MAP) to baseline values, whereas rHb1.1 increased MAP to 27% above the baseline value. Mesenteric vascular resistance after resuscitation with rHb2.0 was 57% less than that with rHb1.1. rHb2.0 was found to have 55% greater intestinal oxygen delivery (Do2int ) and resulted in a 27% lower oxygen-extraction rate than did rHb1.1 after resuscitation. Intestinal microvascular Po2 , determined on the basis of oxygen-dependent quenching of palladium-porphyrin phosphorescence, revealed no difference between rHb2.0 and rHb1.1. The findings of this study confirm that the well-known pressure effect of HBOCs is caused by their effect on the NO-scavenging rate; recombinant modification of this rate did not increase MAP during resuscitation compared with baseline values. Although systemic vasoconstriction was absent, intestinal vasoconstriction almost negligible, and Do2int greater after resuscitation with rHb2.0, the effect of rHb2.0 on pH, base-excess and microvascular Po2 levels after resuscitation were comparable to those achieved with the use of the albumin solution.
authors.affiliation: Department of Physiology, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands. n.j.raat@amc.uva.nl
authors.forename: Nicolaas J H
authors.initials: NJ
authors.lastname: Raat
authors.forename: Jing-Feng
authors.initials: JF
authors.lastname: Liu
authors.forename: Michael P
authors.initials: MP
authors.lastname: Doyle
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Burhop
authors.forename: Jan
authors.initials: J
authors.lastname: Klein
authors.forename: Can
authors.initials: C
authors.lastname: Ince
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001802:Blood Substitutes / Q000627:therapeutic use*; D004195:Disease Models, Animal; D016166:Free Radical Scavengers / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D006454:Hemoglobins / Q000627:therapeutic use*; D006455:Hemoglobins, Abnormal / Q000627:therapeutic use*; D008297:Male; D008638:Mesenteric Arteries / Q000502:physiology*; D008642:Mesenteric Veins / Q000187:drug effects / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000627:therapeutic use; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D013152:Splanchnic Circulation / Q000187:drug effects* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D001802:Blood Substitutes; D016166:Free Radical Scavengers; C474711:HBOC rHB2.0, human; D006454:Hemoglobins; D006455:Hemoglobins, Abnormal; D011994:Recombinant Proteins; C105876:hemoglobin rHb1.1; D009569:Nitric Oxide; D010100:Oxygen