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Plasma arginase promotes acute lung injury (ALI) in a rat model of trauma/hemorrhage and resuscitation
Author(s) -
Johnson Fruzsina K,
Durante William,
Johnson Robert A,
Stewart Ronald M
Publication year - 2012
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.26.1_supplement.1132.5
Subject(s) - arginase , resuscitation , medicine , lung , packed red blood cells , arginine , endocrinology , anesthesia , andrology , chemistry , blood transfusion , biochemistry , amino acid
Red blood cells (RBC) and liver contain arginase that competes for L‐arginine with nitric oxide (NO) synthase. Low NO levels promote neutrophil activation which is a key mediator 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), CINC‐1 (rat homologue of human IL 8) accumulation (1.5±0.5 vs 66.9±22.6pg/min) and pulmonary protein leak (3.4±1.4 vs 115.3±48.7μg/min) were higher in rats transfused with stored PRBC. In contrast, plasma aspartate aminotransferase activity was not different between rats transfused with fresh or stored PRBC. Transfusion with bovine arginase added to fresh PRBC increased plasma arginase activity (3.4±0.5 U/g protein), pulmonary CINC‐1 accumulation (13.9±7.7μg/min) and protein leak (41.1±8.8μg/min). Conversely, the arginase inhibitor, Nω‐hydroxy‐nor‐L‐arginine (100mg/kg IV) during resuscitation with stored PRBC decreased pulmonary CINC‐1 accumulation by 27% and protein leak by 30%. These data suggest that resuscitation with stored PRBC increases plasma arginase activity which contributes to ALI. Supported by grants AHA 0865241F (FKJ) and NIH HL074966 (WD).