title: Adverse effects of hemorrhagic shock resuscitation with stored blood are ameliorated by inhaled nitric oxide in lambs*.
abstract: OBJECTIVE
  Transfusion of stored RBCs is associated with increased morbidity and mortality in trauma patients. Plasma hemoglobin scavenges nitric oxide, which can cause vasoconstriction, induce inflammation, and activate platelets. We hypothesized that transfusion of RBCs stored for prolonged periods would induce adverse effects (pulmonary vasoconstriction, tissue injury, inflammation, and platelet activation) in lambs subjected to severe hemorrhagic shock and that concurrent inhalation of nitric oxide would prevent these adverse effects.
  
  
  METHODS
  Animal study.
  
  
  METHODS
  Research laboratory at the Massachusetts General Hospital, Boston, MA.
  
  
  METHODS
  Seventeen awake Polypay-breed lambs.
  
  
  METHODS
  Lambs were subjected to 2 hours of hemorrhagic shock by acutely withdrawing 50% of their blood volume. Lambs were resuscitated with autologous RBCs stored for 2 hours or less (fresh) or 39 ± 2 (mean ± SD) days (stored). Stored RBCs were administered with or without breathing nitric oxide (80 ppm) during resuscitation and for 21 hours thereafter.
  
  
  RESULTS
  We measured hemodynamic and oxygenation variables, markers of tissue injury and inflammation, plasma hemoglobin concentrations, and platelet activation. Peak pulmonary arterial pressure was higher after resuscitation with stored than with fresh RBCs (24 ± 4 vs 14 ± 2 mm Hg, p < 0.001) and correlated with peak plasma hemoglobin concentrations (R = 0.56, p = 0.003). At 21 hours after resuscitation, pulmonary myeloperoxidase activity was higher in lambs resuscitated with stored than with fresh RBCs (11 ± 2 vs 4 ± 1 U/g, p = 0.007). Furthermore, transfusion of stored RBCs increased plasma markers of tissue injury and sensitized platelets to adenosine diphosphate activation. Breathing nitric oxide prevented the pulmonary hypertension and attenuated the pulmonary myeloperoxidase activity, as well as tissue injury and sensitization of platelets to adenosine diphosphate.
  
  
  CONCLUSIONS
  Our data suggest that resuscitation of lambs from hemorrhagic shock with autologous stored RBCs induces pulmonary hypertension and inflammation, which can be ameliorated by breathing nitric oxide.
authors.affiliation: 1Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA. 2Department of Anesthesia, General Intensive Care, and Pain Management, Medical University of Vienna, Vienna, Austria. 3Blood Transfusion Service of the Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA. 4Cardiovascular Research Center and Cardiology Division of the Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
authors.forename: David M
authors.initials: DM
authors.lastname: Baron
authors.forename: Arkadi
authors.initials: A
authors.lastname: Beloiartsev
authors.forename: Akito
authors.initials: A
authors.lastname: Nakagawa
authors.forename: Trejeeve
authors.initials: T
authors.lastname: Martyn
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Stowell
authors.forename: Rajeev
authors.initials: R
authors.lastname: Malhotra
authors.forename: Claire
authors.initials: C
authors.lastname: Mayeur
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Bloch
authors.forename: Warren M
authors.initials: WM
authors.lastname: Zapol
mesh_terms: D000818:Animals; D017707:Erythrocyte Transfusion / Q000009:adverse effects / Q000379:methods*; D015870:Gene Expression; D006439:Hemodynamics; D006976:Hypertension, Pulmonary / Q000209:etiology; D008168:Lung / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D009569:Nitric Oxide / Q000009:adverse effects / Q000627:therapeutic use*; D009195:Peroxidase / Q000378:metabolism; D012151:Resuscitation / Q000379:methods*; D034561:Sheep, Domestic; D012771:Shock, Hemorrhagic / Q000503:physiopathology* / Q000628:therapy*
chemical_list: D009569:Nitric Oxide; D009195:Peroxidase