title: Hemoglobin-based oxygen carrier provides heterogeneous microvascular oxygenation in heart and gut after hemorrhage in pigs.
abstract: BACKGROUND
  In this study, the hypothesis was tested that resuscitation with hemoglobin-based oxygen carriers (HBOCs) affects the oxygenation of the microcirculation differently between and within organs. To this end, we tested the influence of the volume of an HBOC on the microcirculatory oxygenation of the heart and the gut serosa and mucosa in a porcine model of hemorrhage.
  
  
  METHODS
  In anesthetized open-chested pigs (n = 24), a controlled hemorrhage (30 mL/kg over 1 hour) was followed by resuscitation with 10, 20, or 30 mL/kg diaspirin-crosslinked hemoglobin (DCLHb) or isovolemic resuscitation with 30 mL/kg of a 6% hydroxyethyl starch solution (HAES). Measurements included systemic and regional hemodynamic and oxygenation parameters. Microvascular oxygen pressures (microPO2) of the epicardium and the serosa and mucosa of the ileum were measured simultaneously by the palladium-porphyrin phosphorescence technique. Measurements were obtained up to 120 minutes after resuscitation.
  
  
  RESULTS
  After hemorrhage, a low volume of DCLHb restored both cardiac and intestinal microPO2. Resuscitation of gut microPO2 with a low volume of DCLHb was as effective as isovolemic resuscitation with HAES. Higher volumes of DCLHb did not restore cardiac microPO2, as did isovolemic resuscitation with HAES, but increased gut microPO2 to hyperoxic values, dose-dependently. Effects were similar for the serosal and mucosal microPo2. In contrast to a sustained hypertensive effect after resuscitation with DCLHb, effects of DCLHb on regional oxygenation and hemodynamics were transient.
  
  
  CONCLUSIONS
  This study showed that a low volume of DCLHb was effective in resuscitation of the microcirculatory oxygenation of the heart and gut back to control levels. Increasing the volume of DCLHb did not cause an additional increase in heart microPO2, but caused hyperoxic microvascular values in the gut to be attained. It is concluded that microcirculatory monitoring in this way elucidates the regional behavior of oxygen transport to the tissue by HBOCs, whereas systemic variables were ineffective in describing their response.
authors.affiliation: Department of Physiology, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: Mat
authors.initials: M
authors.lastname: van Iterson
authors.forename: Martin
authors.initials: M
authors.lastname: Siegemund
authors.forename: Kenneth
authors.initials: K
authors.lastname: Burhop
authors.forename: Can
authors.initials: C
authors.lastname: Ince
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001241:Aspirin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D016903:Drug Monitoring; D005260:Female; D005440:Fluid Therapy / Q000379:methods; D006454:Hemoglobins / Q000494:pharmacology / Q000627:therapeutic use*; D006895:Hydroxyethyl Starch Derivatives / Q000008:administration & dosage* / Q000494:pharmacology; D007082:Ileum / Q000098:blood supply / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D007413:Intestinal Mucosa / Q000098:blood supply / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D008833:Microcirculation / Q000187:drug effects*; D010100:Oxygen / Q000032:analysis / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010496:Pericardium / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D010952:Plasma Substitutes / Q000008:administration & dosage* / Q000494:pharmacology; D012151:Resuscitation / Q000379:methods; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D013552:Swine; D013997:Time Factors
chemical_list: D006454:Hemoglobins; D006895:Hydroxyethyl Starch Derivatives; D010952:Plasma Substitutes; C083478:diaspirin-cross-linked hemoglobin; D001241:Aspirin; D010100:Oxygen