title: Determination of organ-specific anemia tolerance.
abstract: OBJECTIVE
  Utilization of anemia tolerance reduces the need for and risks of perioperative transfusion. Recent publications indicate that the critical limit for oxygen supply might not be the same for each organ system. Therefore, we investigated the effects of acute dilutional anemia on heart, brain, kidneys, liver, small intestine, and skeletal muscle to quantify organ-specific tolerance of different levels of acute anemic hypoxia. We hypothesized that, in some organs, tissue hypoxia occurs before the critical limits of systemic oxygen supply are reached.
  
  
  METHODS
  Laboratory animal experiments.
  
  
  METHODS
  Animal research laboratory at university medical school.
  
  
  METHODS
  A total of 18 domestic pigs of either sex (average weight: 19.6 kg).
  
  
  METHODS
  Animals were anesthetized, ventilated, and randomized into three groups and then hemodiluted by exchange of 6% hydroxyethyl starch (130,000:0.4) for whole blood to the group-specific endpoint: Sham (no hemodilution), Hb4 (hemoglobin 4.3 g/dL), Hbcrit (2.7 g/dL). Subsequently, 10 mg/kg pimonidazole (which forms protein adducts in hypoxic cells) was injected. One hour after injection, tissue samples were collected and analyzed for pimonidazole-protein adduct quantification (dot blot) and as a surrogate for transcriptional activation during hypoxia the expression of vascular endothelial growth factor messenger RNA. Relevant hemodynamic and metabolic parameters were collected.
  
  
  RESULTS
  Hemodynamics, metabolic parameters, or oxygen consumption did not indicate that tissue oxygenation was restricted before reaching Hbcrit. However, kidneys and skeletal muscle showed enhanced pimonidazole binding and vascular endothelial growth factor expression at Hb4. By contrast, liver oxygenation was actually improved at Hb4. Heart, brain, and liver showed no signs of tissue hypoxia at Hb4.
  
  
  CONCLUSIONS
  Heart, brain, kidneys, liver, small intestine, and skeletal muscle experience tissue hypoxia at different degrees of acute anemia, as assessed by the pimonidazole method and vascular endothelial growth factor expression. Further studies are needed to elucidate the mechanisms that determine organ-specific anemia tolerance.
authors: Clinic of Anesthesiology and Intensive Care Medicine, Tuebingen University Hospital, Tuebingen, Germany.
authors: Patrick
authors: P
authors: Lauscher
authors: Harry
authors: H
authors: Kertscho
authors: Olga
authors: O
authors: Schmidt
authors: René
authors: R
authors: Zimmermann
authors: Peter
authors: P
authors: Rosenberger
authors: Kai
authors: K
authors: Zacharowski
authors: Jens
authors: J
authors: Meier
mesh_terms: D000208:Acute Disease; D000740:Anemia / Q000150:complications* / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D015687:Cell Hypoxia; D005260:Female; D006438:Hemodilution; D006439:Hemodynamics; D000860:Hypoxia / Q000139:chemically induced / Q000209:etiology* / Q000378:metabolism*; D002534:Hypoxia, Brain / Q000209:etiology / Q000378:metabolism; D007108:Immune Tolerance; D007421:Intestine, Small / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D009593:Nitroimidazoles; D010101:Oxygen Consumption; D011897:Random Allocation; D013552:Swine; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D009593:Nitroimidazoles; D042461:Vascular Endothelial Growth Factor A; C033815:pimonidazole