title: Pulmonary hypertension and systemic vasoconstriction may offset the benefits of acellular hemoglobin blood substitutes.
abstract: OBJECTIVE
  We tested the hypothesis that the pharmacologic properties of a small volume of alpha alpha-cross-linked hemoglobin (alpha alpha Hb) could effectively resuscitate pigs subjected to hemorrhage.
  
  
  METHODS
  Fourteen pigs hemorrhaged to a mean arterial pressure (MAP) of 40 mm Hg for 60 minutes were treated with a 4-mL/kg 2-minute infusion of 10 g/dL alpha alpha Hb or 7 g/dL human serum albumin, an oncotically matched control solution.
  
  
  RESULTS
  The removal of blood (17 +/- 1.5 mL/kg) caused the typical physiologic responses to hemorrhagic hypovolemia. Infusion of alpha alpha Hb restored mean arterial pressure and coronary perfusion pressure, but cardiac output and mixed venous O2 saturation did not improve significantly. Pulmonary arterial pressure and pulmonary vascular resistance increased markedly and were higher than baseline levels after alpha alpha Hb. Infusion of human serum albumin produced only minor hemodynamic changes. Brain blood flow did improve to baseline values after alpha alpha Hb, but was the only tissue to do so. In the human serum albumin group, superior mesenteric artery blood flow recovered to baseline values, whereas brain blood flow did not. Blood flows to other tissues were similar in both groups.
  
  
  CONCLUSIONS
  Small-volume infusion of alpha alpha Hb restored mean arterial pressure and brain blood flow, but pulmonary hypertension and low peripheral perfusion may offset benefits for trauma patients.
authors.affiliation: Department of Cardiopneumology, INCOR, FMUSP, Universidade de São Paulo, Brazil.
authors.forename: L F
authors.initials: LF
authors.lastname: de Figueiredo
authors.forename: M
authors.initials: M
authors.lastname: Mathru
authors.forename: D
authors.initials: D
authors.lastname: Solanki
authors.forename: V W
authors.initials: VW
authors.lastname: Macdonald
authors.forename: J
authors.initials: J
authors.lastname: Hess
authors.forename: G C
authors.initials: GC
authors.lastname: Kramer
mesh_terms: D000418:Albumins / Q000627:therapeutic use; D000818:Animals; D001241:Aspirin / Q000009:adverse effects / Q000031:analogs & derivatives*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003251:Constriction, Pathologic / Q000139:chemically induced; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D006454:Hemoglobins / Q000009:adverse effects*; D006976:Hypertension, Pulmonary / Q000139:chemically induced*; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D012771:Shock, Hemorrhagic / Q000628:therapy*; D013152:Splanchnic Circulation / Q000187:drug effects; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D000418:Albumins; D006454:Hemoglobins; C053936:hemoglobin XL99alpha; D001241:Aspirin