title: Acute isovolemic hemodilution triggers proinflammatory and procoagulatory endothelial activation in vital organs: role of erythrocyte aggregation.
abstract: OBJECTIVE
  The essential role of erythrocytes as oxygen carriers is historically well established, but their function to aggregate and the consequences on the microcirculation is under debate. The pathogenic potential of low erythrocyte aggregation could be important for patients undergoing on-pump cardipopulmonary bypass. These patients are severely hemodiluted due to preoperative isovolemic hemodilution (IHD), circuit priming, and large fluid infusions perioperatively. Considering the vascular endothelium sensitivity to variations in blood rheology, the authors hypothesize that low erythrocyte aggregation will be responsible for activation of vascular endothelium during acute IHD.
  
  
  METHODS
  Acute IHD (30 mL/kg exchange transfusion with colloid solutions) was induced in an "aggregating species"(pigs, n = 15). The hypoxic oxidative stress (plasma malondialdehyde, ex vivo oxygen radicals production in heart, lung, kidney, liver, and ileum tissue biopsies), erythrocyte aggregation (LORCA), and endothelial activation (real-time quantitative RT-PCR on von Willebrand factor (vWF), E- and P-selectins, endothelial nitric oxide synthase gene-expression in tissue biopsies) were investigated.
  
  
  RESULTS
  The production of superoxide and hydroxyl radicals, measured as H2O2 generation, was similar at all times in sham-operated and hemodiluted animals, proving a maintained oxygen delivery to tissues. Acute IHD was followed by a dramatic drop in erythrocyte aggregation and immediate prothrombotic (significant vWF mRNA upregulation in heart, lungs, kidney, liver, ileum) and proinflammatory (significant E- and P-selectins mRNA upregulation in lungs and ileum) endothelial activation. Low erythrocyte aggregation was significantly correlated with increased mRNA-expression of vWF (heart, liver, ileum) and P-selectin (lungs, ileum, and heart).
  
  
  CONCLUSIONS
  These results suggest that low erythrocyte aggregation might trigger endothelium-dependent thrombogenic and proinflammatory response during acute isovolemic hemodilution.
authors.affiliation: Department of Biomedical Engineering/Artificial Organs, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Aurora M
authors.initials: AM
authors.lastname: Morariu
authors.forename: Mark-Hugo J
authors.initials: MH
authors.lastname: Maathuis
authors.forename: Sigridur A
authors.initials: SA
authors.lastname: Asgeirsdottir
authors.forename: Henri G D
authors.initials: HG
authors.lastname: Leuvenink
authors.forename: Piet W
authors.initials: PW
authors.lastname: Boonstra
authors.forename: Wim
authors.initials: W
authors.lastname: van Oeveren
authors.forename: Rutger J
authors.initials: RJ
authors.lastname: Ploeg
authors.forename: Ingrid
authors.initials: I
authors.lastname: Molema
authors.forename: Gerhard
authors.initials: G
authors.lastname: Rakhorst
mesh_terms: D000818:Animals; D001777:Blood Coagulation; D001794:Blood Pressure; D001810:Blood Volume; D001026:Coronary Artery Bypass / Q000009:adverse effects; D019040:E-Selectin / Q000235:genetics; D004730:Endothelium, Vascular / Q000503:physiopathology*; D004903:Erythrocyte Aggregation; D006339:Heart Rate; D006438:Hemodilution / Q000009:adverse effects*; D018056:Hemorheology; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D008315:Malondialdehyde / Q000097:blood; D023421:Models, Animal; D018384:Oxidative Stress; D019007:P-Selectin / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013552:Swine; D014841:von Willebrand Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D019040:E-Selectin; D019007:P-Selectin; D012333:RNA, Messenger; D014841:von Willebrand Factor; D008315:Malondialdehyde