title: Pulmonary hypertension in lambs transfused with stored blood is prevented by breathing nitric oxide.
abstract: BACKGROUND
  During extended storage, erythrocytes undergo functional changes. These changes reduce the viability of erythrocytes leading to release of oxyhemoglobin, a potent scavenger of nitric oxide. We hypothesized that transfusion of ovine packed erythrocytes (PRBC) stored for prolonged periods would induce pulmonary vasoconstriction in lambs, and that reduced vascular nitric oxide concentrations would increase this vasoconstrictor effect.
  
  
  METHODS
  We developed a model of autologous stored blood transfusion in lambs (n = 36). Leukoreduced blood was stored for either 2 days (fresh PRBC) or 40 days (stored PRBC). Fresh or stored PRBC were transfused into donors instrumented for awake hemodynamic measurements. Hemodynamic effects of PRBC transfusion were also studied after infusion of N-nitro-L-arginine methyl-ester (25 mg/kg) or during inhalation of nitric oxide (80 ppm).
  
  
  RESULTS
  Cell-free hemoglobin levels were higher in the supernatant of stored PRBC than in supernatant of fresh PRBC (Mean ± SD, 148 ± 20 vs. 41 ± 13 mg/dl, respectively, P < 0.001). Pulmonary artery pressure during transfusion of stored PRBC transiently increased from 13 ± 1 to 18 ± 1 mmHg (P < 0.001) and was associated with increased plasma hemoglobin concentrations. N-nitro-L-arginine methyl-ester potentiated the increase in pulmonary arterial pressure induced by transfusing stored PRBC, whereas inhalation of nitric oxide prevented the vasoconstrictor response.
  
  
  CONCLUSIONS
  Our results suggest that patients with reduced vascular nitric oxide levels because of endothelial dysfunction may be more susceptible to adverse effects of transfusing blood stored for prolonged periods. These patients might benefit from transfusion of fresh PRBC, when available, or inhaled nitric oxide supplementation to prevent the pulmonary hypertension associated with transfusion of stored PRBC.
authors.affiliation: Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114-2696, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Baron
authors.forename: Binglan
authors.initials: B
authors.lastname: Yu
authors.forename: Chong
authors.initials: C
authors.lastname: Lei
authors.forename: Aranya
authors.initials: A
authors.lastname: Bagchi
authors.forename: Arkadi
authors.initials: A
authors.lastname: Beloiartsev
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Stowell
authors.forename: Andrea U
authors.initials: AU
authors.lastname: Steinbicker
authors.forename: Rajeev
authors.initials: R
authors.lastname: Malhotra
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Bloch
authors.forename: Warren M
authors.initials: WM
authors.lastname: Zapol
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000831:Animals, Newborn; D017707:Erythrocyte Transfusion / Q000009:adverse effects*; D006976:Hypertension, Pulmonary / Q000209:etiology* / Q000276:immunology / Q000517:prevention & control*; D009569:Nitric Oxide / Q000008:administration & dosage*; D034561:Sheep, Domestic; D013997:Time Factors
chemical_list: D009569:Nitric Oxide