title: MalPEG-hemoglobin (MP4) improves hemodynamics, acid-base status, and survival after uncontrolled hemorrhage in anesthetized swine.
abstract: OBJECTIVE
  MalPEG-hemoglobin, 4 g/dL (MP4), is a hemoglobin-based oxygen carrier with a low hemoglobin concentration, low P50 (oxygen half-saturation pressure of hemoglobin), high colloid osmotic pressure, and high viscosity. This study evaluated resuscitation with MP4 in anesthetized swine hemorrhaged 250 mL by controlled withdrawal, followed by a 5-mm tear in the abdominal aorta.
  
  
  METHODS
  Randomized, unblinded.
  
  
  METHODS
  Academic animal laboratory.
  
  
  METHODS
  Anesthetized male and female Swedish Landrace pigs.
  
  
  METHODS
  Four groups of pigs (n = 7 each) were randomized after hemorrhage by aortic tear to receive 250 mL of MP4, Ringer's acetate, 10% pentastarch, or 4 g/dL of stroma-free hemoglobin, followed by aortic repair and transfusion of 250 mL of autologous blood. End points were 20-hr survival, hemodynamic variables, and acid-base status.
  
  
  RESULTS
  Measurements included continuous aortic, pulmonary arterial, and central venous pressures, cardiac output by thermodilution, arterial and venous blood gases; electrolytes; lactate; base excess; oxygen delivery, consumption, and extraction ratio; hematocrit; hemoglobin; and urine output. Body weight (24-27 kg) and hemorrhage volume (26-33 mL/kg) were similar in the four groups. The nadir of mean arterial pressure (22-28 mm Hg) and the increase in lactic acid (5-8 mEq/L) after hemorrhage were similar in all groups, indicating equivalent shock in the four groups. Survival was greatest in the MP4-treated animals (six of seven) compared with Ringer's acetate (two of seven), 10% pentastarch (one of seven), and stroma-free hemoglobin (two of seven) and was accompanied by an improved recovery of arterial pressure, cardiac output, and lactate. Total hemoglobin concentration was equivalent in all groups. Arterial pressure did not increase above baseline values, and systemic vascular resistance was unchanged following administration of MP4, indicating the lack of peripheral vasoconstriction. Mortality in Ringer's acetate, stroma-free hemoglobin, and 10% pentastarch treated animals was associated with deteriorating acid-base status, low urine output, and hyperkalemia.
  
  
  CONCLUSIONS
  These data demonstrate that restoration of oxygen delivery with a small volume of MP4 yields significant recovery from hemorrhage without systemic vasoconstriction.
authors.affiliation: Sangart, San Diego, CA, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Young
authors.forename: Louis
authors.initials: L
authors.lastname: Riddez
authors.forename: Bengt Thomas
authors.initials: BT
authors.lastname: Kjellström
authors.forename: Jenny
authors.initials: J
authors.lastname: Bursell
authors.forename: Ford
authors.initials: F
authors.lastname: Winslow
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lohman
authors.forename: Robert M
authors.initials: RM
authors.lastname: Winslow
mesh_terms: D000136:Acid-Base Equilibrium / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D001802:Blood Substitutes / Q000627:therapeutic use*; D002302:Cardiac Output / Q000187:drug effects; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006454:Hemoglobins / Q000627:therapeutic use*; D008297:Male; D008301:Maleimides / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011897:Random Allocation; D012771:Shock, Hemorrhagic / Q000401:mortality / Q000628:therapy*; D016019:Survival Analysis; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D001802:Blood Substitutes; D006454:Hemoglobins; D008301:Maleimides; C493836:maleimide-polyethylene glycol-modified hemoglobin, MP4; D011092:Polyethylene Glycols