title: Dose-response relationship between aortic infusions of polymerized bovine hemoglobin and return of circulation in a canine model of ventricular fibrillation and advanced cardiac life support.
abstract: OBJECTIVE
  Return of spontaneous circulation after cardiac arrest may be a function of vital organ perfusion. Selective aortic perfusion and oxygenation with oxygenated ultrapurified polymerized bovine hemoglobin improves vital organ perfusion and is an effective adjunct in the treatment of cardiac arrest. This study determined the dose-response relationship between intra-aortic oxygenated ultrapurified polymerized bovine hemoglobin and return of spontaneous circulation.
  
  
  METHODS
  Randomized, interventional study, using a clinically relevant model of ventricular fibrillation with a prolonged arrest time and cardiopulmonary resuscitation based on external chest compression and aortic occlusion with oxygenated ultrapurified polymerized bovine hemoglobin infusion.
  
  
  METHODS
  University, resuscitation research laboratory.
  
  
  METHODS
  Fasted, mongrel dogs (> 20 kg).
  
  
  METHODS
  After alpha-chloralose anesthesia, blood gases and vital signs were normalized. Electrocardiogram, aortic arch, and intraesophageal pressures were measured continuously. A descending aortic occlusion-infusion balloon catheter was placed through the femoral artery. Ventricular fibrillation was induced and basic life support was begun after 10 mins. Interanimal differences in basic life support were minimized by standardization of the esophageal pulse pressure and aortic blood gases. At 13 mins, the aortic occlusion balloon was inflated and a dose of 10, 20, or 30 mL/kg of ultrapurified polymerized bovine hemoglobin was infused at 300 mL/min. Defibrillation was attempted at the end of the infusion.
  
  
  RESULTS
  Only two of five animals given 10 mL/kg of ultrapurified polymerized bovine hemoglobin had return of spontaneous circulation, vs. four of five animals given 20 mL/kg, and all seven animals given 30 mL/kg. All resuscitated animals were alive at 1 hr after return of spontaneous circulation.
  
  
  CONCLUSIONS
  There is a dose-response relationship between the volume of oxygenated ultrapurified polymerized bovine hemoglobin administered by selective aortic perfusion and oxygenation and return of spontaneous circulation after prolonged cardiac arrest. This result supports the hypothesis that vital organ flow is causally related to improved outcome.
authors.affiliation: Department of Medicine, Columbia Presbyterian Medical Center, Columbia University College of Physicians and Surgeons, New York, NY, USA.
authors.forename: N A
authors.initials: NA
authors.lastname: Paradis
mesh_terms: D000818:Animals; D001011:Aorta; D001802:Blood Substitutes / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006439:Hemodynamics; D006454:Hemoglobins / Q000627:therapeutic use*; D007261:Infusions, Intra-Arterial; D011108:Polymers / Q000627:therapeutic use*; D011897:Random Allocation; D014693:Ventricular Fibrillation / Q000188:drug therapy* / Q000503:physiopathology*
chemical_list: D001802:Blood Substitutes; D006454:Hemoglobins; D011108:Polymers