title: Examining and mitigating acellular hemoglobin vasoactivity.
abstract: CONCLUSIONS
  There has been a striking advancement in our understanding of red cell substitutes over the past decade. Although regulatory oversight has influenced many aspects of product development in this period, those who have approached the demonstration of efficacy of red cell substitutes have failed to understand their implication at the level of the microcirculation, where blood interacts closely with tissue.
  
  
  BACKGROUND
  The understanding of the adverse effects of acellular hemoglobin (Hb)-based oxygen carriers (HBOCs) has fortunately expanded from Hb-induced renal toxicity to a more complete list of biochemical mechanism. In addition, various unexpected adverse reactions were seen in early clinical studies. The effects of the presence of acellular Hb in plasma are relatively unique because of the convergence of mechanical and biochemical natures.
  
  
  RESULTS
  Controlling the variables using genetic engineering and chemical modification to change specific characteristics of the Hb molecule may allow for solving the complex multivariate problems of acellular Hb vasoactivity. HBOCs may never be rendered free of negative effects; however, quantifying the nature and extent of microvascular complications establishes a platform for designing new ameliorative therapies.
  
  
  CONCLUSIONS
  It is time to leave behind the study of vasoactivity and toxicity based on bench-top measurements of biochemical changes and those based solely on systemic parameters in vivo, and move to a more holistic analysis of the mechanisms creating the problems, complemented with meaningful studies of efficacy.
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA. pcabrales@ucsd.edum
authors.forename: Pedro
authors.initials: P
authors.lastname: Cabrales
mesh_terms: D000818:Animals; D001802:Blood Substitutes; D001808:Blood Vessels / Q000502:physiology*; D006454:Hemoglobins / Q000737:chemistry / Q000502:physiology*; D006470:Hemorrhage / Q000503:physiopathology; D006801:Humans; D010084:Oxidation-Reduction; D065227:Transfusion Reaction
chemical_list: D001802:Blood Substitutes; D006454:Hemoglobins