title: Effects of low-volume hemoglobin glutamer-200 versus normal saline and arginine vasopressin resuscitation on systemic and skeletal muscle blood flow and oxygenation in a canine hemorrhagic shock model.
abstract: OBJECTIVE
  To test the hypothesis that low-volume resuscitation with hemoglobin glutamer-200 improves hemodynamic function and tissue oxygenation, whereas arginine vasopressin resuscitation improves blood pressures more than low-volume saline or hemoglobin glutamer infusion but compromises systemic and muscle blood flow and oxygenation.
  
  
  METHODS
  Randomized laboratory investigation.
  
  
  METHODS
  University research facility.
  
  
  METHODS
  Nineteen dogs.
  
  
  METHODS
  Dogs were instrumented to determine heart rate; arterial, central venous, pulmonary arterial, and pulmonary arterial occlusion pressures; cardiac output; and quadriceps muscle blood flow and oxygen tension (PMo2). Total and plasma hemoglobin, oxygen content, lactate, pH, standard base excess, and arginine vasopressin levels were determined, and systemic oxygen delivery (Do2I) and extraction ratio were calculated. Measurements were made before and 30 mins following hemorrhage. Dogs were resuscitated over 60 mins with saline (8.5 mL/kg), arginine vasopressin (0.4 IU/kg bolus plus 0.08 IU x kg x min), or 1:1 diluted hemoglobin glutamer-200. Recordings were then repeated. Subsequently, animals received 30 mL/kg shed blood (60 mL x kg x hr), and recordings were repeated immediately and 1 hr later.
  
  
  RESULTS
  Hemorrhage ( approximately 52 mL/kg) caused characteristic changes in hemodynamic, hematologic, systemic PMo2, and acid-base variables. Saline resuscitation increased both Do2I and muscle perfusion by 42% and 51%, while arginine vasopressin treatment reduced heart rate by 31% and increased mean arterial pressure by 22% but not cardiac output, Do2I, or muscle blood flow, resulting in a further decrease of PMo2 by 68% and worse metabolic acidosis. Hemoglobin glutamer-200 infusion caused systemic and pulmonary vasoconstriction, however, without deterioration of cardiac output, Do2I, muscle blood flow, or PMo2 despite lack of oxygen content increase. Blood transfusion restored most variables.
  
  
  CONCLUSIONS
  Low-volume crystalloid or hemoglobin glutamer-200 resuscitation posthemorrhage may improve (but not restore) macro- and microvascular functions and tissue oxygenation, while arginine vasopressin infusion may only improve blood pressures and result in lower overall systemic perfusion compared with low-volume saline or hemoglobin glutamer-200 treatment and worsening of anaerobic conditions in skeletal muscle.
authors.affiliation: University of Pennsylvania, School of Veterinary Medicine, Department of Clinical Studies, Section of Critical Care, New Bolton Center, Kennett Square, PA, USA. driessen@vet.upenn.edu
authors.forename: Bernd
authors.initials: B
authors.lastname: Driessen
authors.forename: Laura
authors.initials: L
authors.lastname: Zarucco
authors.forename: Robert A
authors.initials: RA
authors.lastname: Gunther
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Burns
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Lamb
authors.forename: Stella E
authors.initials: SE
authors.lastname: Vincent
authors.forename: Ray A
authors.initials: RA
authors.lastname: Boston
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Jahr
authors.forename: Anthony T W
authors.initials: AT
authors.lastname: Cheung
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000008:administration & dosage*; D001775:Blood Circulation / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006454:Hemoglobins / Q000008:administration & dosage*; D008297:Male; D009132:Muscles / Q000098:blood supply*; D010100:Oxygen / Q000378:metabolism; D011897:Random Allocation; D012151:Resuscitation / Q000379:methods*; D012771:Shock, Hemorrhagic / Q000503:physiopathology / Q000628:therapy*
chemical_list: D006454:Hemoglobins; C402601:hemoglobin glutamer-200; D001127:Arginine Vasopressin; D010100:Oxygen