title: Hemoglobin vesicles reduce hypoxia-related inflammation in critically ischemic hamster flap tissue.
abstract: OBJECTIVE
  The aim of this study was to investigate the effect of a highly viscous, left-shifted hemoglobin vesicle solution (HbV) on the hypoxia-related inflammation and the microcirculation in critically ischemic peripheral tissue.
  
  
  METHODS
  Randomized prospective study.
  
  
  METHODS
  University laboratory.
  
  
  METHODS
  Twenty-four male golden Syrian hamsters.
  
  
  METHODS
  Island flaps were dissected from the back skin of anesthetized hamsters for assessment with intravital microscopy. The flap included a critically ischemic, hypoxic area that was perfused via a collateralized vasculature. One hour after completion of the preparation, the animals received an injection of 25% of total blood volume of 0.9% NaCl or NaCl suspended with HbVs at a concentration of 5 g/dL (HbV5) or 10 g/dL (HbV10).
  
  
  RESULTS
  Plasma viscosity was increased from 1.32 cP to 1.61 cP and 2.14 cP after the administration of HbV5 and HbV10, respectively (both p < .01). Both HbV solutions raised partial oxygen tension (Clark-type microprobes) in the ischemic tissue from approximately 10 torr to 17 torr (p < .01), which was paralleled by an increase in capillary perfusion by > 200% (p < .01). The 50% increase in macromolecular capillary leakage found over time in the control animals was completely abolished by the HbV solutions (p < .01), which was accompanied by a > 50% (p < .01) reduction in cells immunohistochemically stained for tumor necrosis factor-alpha and interleukin-6 and in leukocyte counts, whereas no such changes were observed in the anatomically perfused, normoxic tissue.
  
  
  CONCLUSIONS
  Our study suggests that in critically ischemic, hypoxic peripheral tissue, hypoxia-related inflammation may be reduced by a top-load infusion of HbV solutions. We attributed this effect to a restoration of tissue oxygenation and an increase in plasma viscosity, both of which may have resulted in attenuation of secondary microcirculatory impairments.
authors.affiliation: Department of Orthopedic, Plastic and Hand Surgery, Inselspital University Hospital, Berne, Switzerland.
authors.forename: Jan A
authors.initials: JA
authors.lastname: Plock
authors.forename: Annemarie E
authors.initials: AE
authors.lastname: Tromp
authors.forename: Claudio
authors.initials: C
authors.lastname: Contaldo
authors.forename: Timo
authors.initials: T
authors.lastname: Spanholtz
authors.forename: Dubravko
authors.initials: D
authors.lastname: Sinovcic
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sakai
authors.forename: Eishun
authors.initials: E
authors.lastname: Tsuchida
authors.forename: Michael
authors.initials: M
authors.lastname: Leunig
authors.forename: Andrej
authors.initials: A
authors.lastname: Banic
authors.forename: Dominique
authors.initials: D
authors.lastname: Erni
mesh_terms: D000818:Animals; D001802:Blood Substitutes / Q000494:pharmacology*; D001809:Blood Viscosity / Q000187:drug effects; D019559:Capillary Leak Syndrome / Q000503:physiopathology; D003097:Collateral Circulation / Q000187:drug effects; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D006454:Hemoglobins / Q000494:pharmacology*; D000860:Hypoxia / Q000503:physiopathology*; D015850:Interleukin-6 / Q000378:metabolism; D007511:Ischemia / Q000503:physiopathology*; D008081:Liposomes; D008233:Lymphotoxin-alpha / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D008833:Microcirculation / Q000187:drug effects; D010100:Oxygen / Q000097:blood; D012039:Regional Blood Flow / Q000187:drug effects; D013524:Surgical Flaps / Q000098:blood supply*
chemical_list: D001802:Blood Substitutes; D006454:Hemoglobins; D015850:Interleukin-6; D008081:Liposomes; D008233:Lymphotoxin-alpha; D010100:Oxygen