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Increased plasma arginase activity contributes to acute lung injury (ALI) following resuscitation with stored packed red blood cells (PRBC) in a rat model of trauma/hemorrhage
Author(s) -
Johnson Fruzsina K,
Durante William,
Johnson Robert A,
Craig Teresa,
Myers John G,
Stewart Ronald M
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.642.3
Red blood cells (RBC) and liver express arginase that competes for L‐arginine with nitric oxide (NO) synthase and decreases NO production. Low NO levels promote neutrophil activation which is a key feature of ALI. Arginase is released during RBC storage and ischemic liver damage. Massive hemorrhage promotes liver ischemia and is treated by RBC transfusion. This study tests the hypothesis that increased plasma arginase activity contributes to ALI following resuscitation with stored PRBC in a rat model of trauma/hemorrhage. PRBC were prepared from rat whole blood. Male Lewis rats were implanted with femoral arterial and venous catheters (trauma), subjected to a 30% hemorrhage and resuscitated with crystalloids and fresh or stored (28 days) PRBC. Plasma arginase activity (0.2±0.1 vs 3.1±1.1 U/g protein) and pulmonary protein leak (3.4±1.4 vs 115.3±48.7μg/min) were higher in rats transfused with stored PRBC. Transfusion with bovine arginase added to fresh PRBC increased plasma arginase activity (3.4±0.5 U/g protein) and pulmonary protein leak (41.1±8.8μg/min). Conversely, L‐arginine administration (300mg/kg IV) prior to resuscitation with stored PRBC decreased pulmonary protein leak by 47%. These data suggest that resuscitation with stored PRBC increases plasma arginase activity which contributes to ALI by decreasing L‐arginine availability. Supported by grants AHA 0865241F (FKJ) and NIH HL074966 (WD).