PLASMA AND LIPIDS FROM STORED PACKED RED-BLOOD-CELLS CAUSE ACUTE LUNGINJURY IN AN ANIMAL-MODEL

Transfusion-related acute lung injury (TRALI) is a serious complicatio n of hemotherapy. During blood storage, lipids are generated and relea sed into the plasma. In this study, the role of these lipids in TRALI it as investigated using an isolated, perfused rat lung model, Rats we re pretreated with endotoxin (LPS) or saline in vivo and the lungs wer e isolated, ventilated, and perfused with saline, or (a) 5% (vol/vol) fresh human plasma, (b) plasma from stored blood from the day of isola tion (D.0) or from the day of outdate (D.42), (c) lipid extracts from D.42 plasma, or (d) purified lysophosphatidylcholines. Lungs from sali ne or LPS-pretreated rats perfused with fresh (D.0) plasma showed no p ulmonary damage as compared with saline perfused controls, LPS pretrea tment/D.42 plasma perfusion caused acute lung injury (ALI) manifested by dramatic changes in both pulmonary artery pressure and edema, incub ation of LPS pre-tx rats with mibefradil, a Ca2+ channel blocker, or W EB 2170, a platelet-activating factor (PAF) receptor antagonist, inhib ited ALI caused by D.42 plasma, Lung histology showed neutrophil seque stration without ALI with LPS pretreatment/saline or D.0 plasma perfus ion, but ALI with LPS pretreatment/D.42 plasma perfusion, and inhibiti on of D.42 plasma induced ALI with WEB 2170 or mibefradil. A significa nt increase in leukotriene E4 was present in LPS-pretreated/D.42 plasm a-perfused lungs that was inhibited by WEB 2170, Lastly, significant p ulmonary edema was produced when lipid extracts of D.42 plasma or lyso phosphatidylcholines were perfused into LPS-pretreated lungs, Lipids c aused ALI without vasoconstriction, except at the highest dose employe d. In conclusion, both plasma and lipids from stored blood produced pu lmonary damage in a model of acute lung injury, TRALI, like the adult respiratory distress syndrome, may be the result of two insults: one d erived from stored blood and the other from the clinical condition of the patient.