Red blood cell storage in additive solution-7 preserves energy and redox metabolism: a metabolomics approach

BACKGROUND: Storage and transfusion of red blood cells (RBCs) has a huge medical and economic impact. Routine storage practices can be ameliorated through the implementation of novel additive solutions (ASs) that tackle the accumulation of biochemical and morphologic lesion during routine cold liquid storage in the blood bank, such as the recently introduced alkaline solution AS-7. Here we hypothesize that AS-7 might exert its beneficial effects through metabolic modulation during routine storage. STUDY DESIGN AND METHODS: Apheresis RBCs were resuspended either in control AS-3 or experimental AS-7, before ultrahigh-performance liquid chromatography-mass spectrometry metabolomics analysis. RESULTS: Unambiguous assignment and relative quantitation was achieved for 229 metabolites. AS-3 and AS-7 results in many similar metabolic trends over storage, with AS-7 RBCs being more metabolically active in the first storage week. AS-7 units had faster fueling of the pentose phosphate pathway, higher total glutathione pools, and increased flux through glycolysis as indicated by higher levels of pathway intermediates. Metabolite differences are especially observed at 7 days of storage, but were still maintained throughout 42 days. CONCLUSION: AS-7 formulation (chloride free and bicarbonate loading) appears to improve energy and redox metabolism in stored RBCs in the early storage period, and the differences, though diminished, are still appreciable by Day 42. Energy metabolism and free fatty acids should be investigated as potentially important determinants for preservation of RBC structure and function. Future studies will be aimed at identifying metabolites that correlate with in vitro and in vivo circulation times.