Red blood cell washing, nitrite therapy, and antiheme therapies prevent stored red blood cell toxicity after trauma–hemorrhage

• Published in: Free radical biology & medicine 2015-08, Vol.85, p.207-218
• Main Authors: Stapley, Ryan, Rodriguez, Cilina, Oh, Joo-Yeun, Honavar, Jaideep, Brandon, Angela, Wagener, Brant M., Marques, Marisa B., Weinberg, Jordan A., Kerby, Jeffrey D., Pittet, Jean-Francois, Patel, Rakesh P.
• Format: Article
• Language: English
• Subjects: Acute lung injury; Animals; Erythrocytes - cytology; Heme; Heme - antagonists & inhibitors; Hemin; Hemoglobin; Hemorrhage - therapy; Humans; Mice; Mice, Inbred C57BL; Nitric oxide; Nitrites - administration & dosage; Resuscitation; Storage lesion; Wounds and Injuries - therapy
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2015.04.025

Transfusion of stored red blood cells (RBCs) is associated with increased morbidity and mortality in trauma patients. Pro-oxidant, pro-inflammatory, and nitric oxide (NO) scavenging properties of stored RBCs are thought to underlie this association. In this study we determined the effects of RBC washing and nitrite and antiheme therapy on stored RBC-dependent toxicity in the setting of trauma-induced hemorrhage. A murine (C57BL/6) model of trauma–hemorrhage and resuscitation with 1 or 3 units of RBCs stored for 0–10 days was used. Tested variables included washing RBCs to remove lower MW components that scavenge NO, NO-repletion therapy using nitrite, or mitigation of free heme toxicity by heme scavenging or preventing TLR4 activation. Stored RBC toxicity was determined by assessment of acute lung injury indices (airway edema and inflammation) and survival. Transfusion with 5 day RBCs increased acute lung injury indexed by BAL protein and neutrophil accumulation. Washing 5 day RBCs prior to transfusion did not decrease this injury, whereas nitrite therapy did. Transfusion with 10 day RBCs elicited a more severe injury resulting in ~90% lethality, compared to