Zimring, J C, et al., Strain-Specific Rbc Storage, Metabolism, and Eicosanoid Generation in a Mouse Model. Transfusion, 2013.
Red blood cell (RBC) transfusion is alifesaving therapy, the logistic implementation of whichrequires RBC storage. However, stored RBCs exhibitsubstantial donor variability in multiple characteristics,including hemolysis in vitro and RBC recovery in vivo.The basis of donor variability is poorly understood.
STUDY DESIGN AND METHODS:
We applied amurine model of RBC storage and transfusion to testthe hypothesis that genetically distinct inbred strains ofmice would demonstrate strain-specific differences inRBC storage. In vivo recoveries were determined bymonitoring transfused RBCs over 24 hours. Timed aliquotsof stored RBCs were subjected to tandemchromatography/mass spectrometry analysis to elucidatemetabolic changes in the RBCs during storage.
Using independent inbred mouse strains asdonors, we found substantial strain-specific differencesin posttransfusion RBC recovery in vivo after standardizedrefrigerated storage in vitro. Poor posttransfusionRBC recovery correlated with reproducible metabolicvariations in the stored RBC units, including increasedlipid peroxidation, decreased levels of multiple naturalantioxidants, and accumulation of cytidine. Straindependentdifferences were also observed ineicosanoid generation (i.e., prostaglandins andleukotrienes).
These findings provide the first evidenceof strain-specific metabolomic differences afterrefrigerated storage of murine RBCs. They also providethe first definitive biochemical evidence for strainspecificvariation of eicosanoid generation during RBCstorage. The molecules described that correlate withRBC storage quality, and their associated biochemicalpathways, suggest multiple causal hypotheses that canbe tested regarding predicting the quality of RBC unitsbefore transfusion and developing methods of improvedRBC storage.