title: Effects of isovolemic resuscitation with hemoglobin-based oxygen carrier Hemoglobin glutamer-200 (bovine) on systemic and mesenteric perfusion and oxygenation in a canine model of hemorrhagic shock: a comparison with 6% hetastarch solution and shed blood.
abstract: OBJECTIVE
  To study Hemoglobin glutamer-200 bovine (Hb-200), 6% hetastarch (HES) and shed whole blood (WB) resuscitation in canine hemorrhagic shock.
  
  
  METHODS
  Prospective laboratory investigation. Animals Twelve adult dogs [29 +/- 1 kg (mean +/- SD)].
  
  
  METHODS
  Anesthetized dogs were instrumented for recording systemic and mesenteric hemodynamic parameters and withdrawal of arterial, mixed and mesenteric venous blood, in which hematological, oxygenation, blood gas and acid-bases variables were determined. Recordings were made before [baseline (BL)], after 1 hour of hypovolemia and immediately and 3 hours post-resuscitation with 30 mL kg(-1) of either Hb-200, HES, or WB.
  
  
  RESULTS
  Blood withdrawal (average 34 +/- 2 mL kg(-1)) caused significant hemodynamic changes, metabolic acidosis and hyperlactatemia characteristic for hemorrhagic shock. Only WB transfusion restored all variables. Hemoglobin glutamer-200 bovine infusion returned most hemodynamic parameters including cardiac output and mesenteric arterial blood flow to BL but increased mean arterial pressure above BL (p < 0.05). However, Hb-200 failed to restore total Hb and arterial oxygen content (CaO2), leaving systemic (DO2I) and mesenteric O2 delivery (DO2Im) below BL (p < 0.05). Nevertheless, acid-base variables recovered completely after Hb-200 resuscitation, and met-hemoglobin (Met-Hb) levels increased (p < 0.05). Hetastarch resuscitation returned hemodynamic variables to or above BL but further decreased total Hb and CaO2, preventing recovery of sDO2I and mDO2I (p < 0.05). Thus, systemic and mesenteric O2 extraction stayed above BL (p < 0.05) while acid-base variables recovered to BL, although slower than in Hb-200 and WB groups (p < 0.05).
  
  
  CONCLUSIONS
  Resuscitation with Hb-200 seemed to resolve metabolic acidosis and lactatemia more rapidly than HES, but not WB; yet it is not superior to HES in improving DO2I and DO2Im. The hyperoncotic property of solutions like Hb-200 that results in rapid volume expansion with more homogenous microvascular perfusion and the ability to facilitate diffusive O2 transfer accelerating metabolic recovery may be the key mechanisms underlying their beneficial effects as resuscitants.
authors.affiliation: Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, PA 19348, USA. driessen@vet.upenn.edu
authors.forename: B
authors.initials: B
authors.lastname: Driessen
authors.forename: J S
authors.initials: JS
authors.lastname: Jahr
authors.forename: F
authors.initials: F
authors.lastname: Lurie
authors.forename: R A
authors.initials: RA
authors.lastname: Gunther
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D001794:Blood Pressure; D001802:Blood Substitutes / Q000008:administration & dosage*; D002302:Cardiac Output; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D006454:Hemoglobins / Q000008:administration & dosage*; D006895:Hydroxyethyl Starch Derivatives / Q000008:administration & dosage*; D008297:Male; D008638:Mesenteric Arteries / Q000502:physiology; D010100:Oxygen / Q000097:blood; D011446:Prospective Studies; D012771:Shock, Hemorrhagic / Q000628:therapy*
chemical_list: D001802:Blood Substitutes; D006454:Hemoglobins; D006895:Hydroxyethyl Starch Derivatives; C402601:hemoglobin glutamer-200; D010100:Oxygen