title: Resuscitation with polyethylene glycol-modified human hemoglobin improves microcirculatory blood flow and tissue oxygenation after hemorrhagic shock in awake hamsters.
abstract: OBJECTIVE
  To determine whether resuscitation with polyethylene glycol-modified human hemoglobin (MalPEG-Hb), an oxygen-carrying blood replacement fluid with 4 g/dL Hb, viscosity of 2.5 cP, colloid osmotic pressure of 49 mm Hg, and p50 of 5.5 mm Hg, improves systemic and microvascular variables after hemorrhage compared with shed blood (SB) and 5% hydroxyethyl starch (HES).
  
  
  METHODS
  Laboratory.
  
  
  METHODS
  Golden Syrian hamsters.
  
  
  METHODS
  Prospective study.
  
  
  METHODS
  Hamsters implemented with a skin fold chamber were hemorrhaged 50% of blood volume and resuscitated with 50% shed blood volume (SB, HES, or MalPEG-Hb).
  
  
  RESULTS
  Shock and resuscitation were monitored for 1 hr each. Microvascular events were characterized in terms of vessel diameter, flow velocity, functional capillary density, and Po(2) in arterioles, venules, and extravascular tissue. Systemic variables include mean arterial pressure, heart rate, Po(2), Pco(2), pH, and base excess. MalPEG-Hb resuscitation increased functional capillary density to 64% vs. 44% for SB and 32% for HES relative to baseline before shock. Microvascular flow increased 16% for MalPEG-Hb relative to baseline and remained decreased by 44% for SB and 80% for HES. Hemoglobin concentration was 10.4 g/dL with SB, 7.5 (6.8 g/dL in red blood cells and 0.9 g/dL in plasma) with MalPEG-Hb, and 7.5 g/dL with HES, leading to tissue Po(2) of 19, 8, and 5 mm Hg respectively. Calculations of oxygen extraction show that 0.9 g/dL of MalPEG-Hb increased oxygen extraction per gram of red cell hemoglobin in the tissue analyzed compared with SB. These measurements correlate well with a systemic indicator of recovery, base excess, 5.4 +/- 4.7 (MalPEG-Hb), 1.7 +/- 3.8 (SB), and -0.3 +/- 5.7 (HES).
  
  
  CONCLUSIONS
  The presence of 0.9 g/dL of high oxygen affinity MalPEG-Hb improves microvascular blood flow and oxygen transport during shock to a significantly greater extent than that attainable with blood or HES.
authors.affiliation: Department of Bioengineering, University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0412, USA. rwetts@bioeng.ucsd.edu
authors.forename: Reto
authors.initials: R
authors.lastname: Wettstein
authors.forename: Amy G
authors.initials: AG
authors.lastname: Tsai
authors.forename: Dominique
authors.initials: D
authors.lastname: Erni
authors.forename: Robert M
authors.initials: RM
authors.lastname: Winslow
authors.forename: Marcos
authors.initials: M
authors.lastname: Intaglietta
mesh_terms: D000818:Animals; D001802:Blood Substitutes / Q000494:pharmacology* / Q000627:therapeutic use; D006224:Cricetinae; D006439:Hemodynamics / Q000187:drug effects; D006454:Hemoglobins / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008647:Mesocricetus; D008833:Microcirculation / Q000187:drug effects*; D010100:Oxygen / Q000378:metabolism; D011092:Polyethylene Glycols / Q000494:pharmacology* / Q000627:therapeutic use; D011446:Prospective Studies; D012771:Shock, Hemorrhagic / Q000097:blood / Q000628:therapy*
chemical_list: D001802:Blood Substitutes; D006454:Hemoglobins; C109960:PEG-hemoglobin; D011092:Polyethylene Glycols; D010100:Oxygen