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

Abstract

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.

Metabolic effect of alkaline additives and guanosine/gluconate in storage solutions for red blood cells

“…Indeed, we recently appreciated the role that oxidative stress plays in activating AMP deaminase 3 to promote purine deamination and thus hypoxanthine accumulation, a phenomenon that negatively correlates with posttransfusion recovery and is prevented by hypoxic storage (which also induces intracellular alkalinization) . However, direct comparison of hypoxanthine levels in alkaline versus nonalkaline additives (SOLX vs. AS‐3) in unpaired studies showed increases in the former group, also accompanied by higher total levels of nondeaminated purines and ATP . Similarly, supplementation of CO 2 to hypoxically stored RBCs decreased hypoxanthine levels but increased urate/hypoxanthine ratios.…”

“…For example, although RBCs lack mitochondria, they have now been shown to metabolize carboxylic acids from citrated anticoagulants or storage additives in an oxygen‐dependent fashion . Omics technologies have helped investigators in the field of transfusion medicine to characterize the multifaceted nature of the storage lesion and, by qualitatively and quantitatively characterizing its evolution in different storage additives, pave the way for future developments in the field. Recently, we performed a comparative analysis of hemolysis, ion homeostasis, and osmotic fragility of RBCs stored in five different additives .…”

pH modulation ameliorates the red blood cell storage lesion in a murine model of transfusion

“…28, 29 These advances naturally led to the study of the metabolomics of the red blood cell storage lesion using emerging technologies. 28, 30-32 …”

AltitudeOmics: Red Blood Cell Metabolic Adaptation to High Altitude Hypoxia

“…MS analyses through a QExactive mass spectrometer (Thermo, San Jose, CA, USA) and metabolite identification through Maven 42 (Princeton, NJ, USA), the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database, and a library of >800 standard compounds (SIGMA Aldrich, St. Louis, MO, USA; MLSMS, IROATech, Bolton, MA, USA) were performed as reported 40,41 .…”