title: Inhaled nitric oxide attenuates the adverse effects of transfusing stored syngeneic erythrocytes in mice with endothelial dysfunction after hemorrhagic shock.
abstract: BACKGROUND
  The authors investigated whether transfusion with stored erythrocytes would increase tissue injury, inflammation, oxidative stress, and mortality (adverse effects of transfusing stored erythrocytes) in a murine model of hemorrhagic shock. They tested whether the adverse effects associated with transfusing stored erythrocytes were exacerbated by endothelial dysfunction and ameliorated by inhaling nitric oxide.
  
  
  METHODS
  The authors studied mice fed a high-fat diet (HFD-fed; to induce endothelial dysfunction) or a standard diet for 4-6 weeks. Mice were subjected to 90 min of hemorrhagic shock, followed by resuscitation with leukoreduced syngeneic erythrocytes stored less than 24 h (fresh erythrocytes) or stored for 2 weeks (stored erythrocytes).
  
  
  RESULTS
  In standard-diet-fed mice at 2 h after resuscitation, transfusion with stored erythrocytes increased tissue injury more than transfusion with fresh erythrocytes. The adverse effects of transfusing stored erythrocytes were more marked in HFD-fed mice and associated with increased lactate levels and short-term mortality. Compared with fresh erythrocytes, resuscitation with stored erythrocytes was associated with a reduction in P50, increased plasma hemoglobin levels, and increased indices of inflammation and oxidative stress, effects that were exacerbated in HFD-fed mice. Inhaled nitric oxide reduced tissue injury, lactate levels, and indices of inflammation and oxidative stress and improved short-term survival in HFD-fed mice resuscitated with stored erythrocytes.
  
  
  CONCLUSIONS
  Resuscitation with stored erythrocytes adversely impacts outcome in mice with hemorrhagic shock, an effect that is exacerbated in mice with endothelial dysfunction. Inhaled nitric oxide reduces tissue injury and improves short-term survival in HFD-fed mice resuscitated with stored erythrocytes.
authors.affiliation: Postdoctoral Fellow, Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care and Pain Medicine, Harvard Medical School at Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Chong
authors.initials: C
authors.lastname: Lei
authors.affiliation: Instructor in Anesthesia, Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care and Pain Medicine, Harvard Medical School at Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Binglan
authors.initials: B
authors.lastname: Yu
authors.affiliation: Instructor in Anesthesia, Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care and Pain Medicine, Harvard Medical School at Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Mohd
authors.initials: M
authors.lastname: Shahid
authors.affiliation: Postdoctoral Fellow, Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care and Pain Medicine, Harvard Medical School at Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Arkadi
authors.initials: A
authors.lastname: Beloiartsev
authors.affiliation: William Thomas Green Morton Professor of Anesthesia, Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care and Pain Medicine, Harvard Medical School at Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Bloch
authors.affiliation: Reginald Jenney Professor of Anesthesia, Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care and Pain Medicine, Harvard Medical School at Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Warren M
authors.initials: WM
authors.lastname: Zapol
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D017707:Erythrocyte Transfusion / Q000009:adverse effects* / Q000592:standards; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000008:administration & dosage*; D012771:Shock, Hemorrhagic / Q000097:blood / Q000401:mortality / Q000628:therapy*; D015996:Survival Rate / Q000639:trends; D013997:Time Factors; D014185:Transplantation, Isogeneic / Q000009:adverse effects
chemical_list: D009569:Nitric Oxide