Sanne de Bruin

135 Metabolic changes in erythrocytes in vivo, during storage and after transfusion oxygenation transport capacity while in critically ill patients these mechanisms are often impaired. Indeed, in severe traumatic brain injured patients an effect of storage time on oxygenation capacity has been observed 69 . RCCs stored for less than 19 days improved the brain oxygenation while longer stored products had no beneficial effect on oxygenation. Pentose phosphate pathway and glutathione metabolism Data on PPP fluxes and glutathionemetabolismof transfused RCCs are still lacking. GSH levels gradually decrease during storage, which can be reversed in vitro using rejuve- nation solutions 65 . Therefore, we hypothesize that GSH levels in transfused cells nor- malize after transfusion. After normalization it is expected that these levels gradually decrease, similar as seen during physiological aging. Furthermore, we hypothesize that the oxidative stress in erythrocytes decreases after transfusion compared to storage. Consequently, less GSH needs to be utilized leading to a decreased flux into the PPP and normalization of GSH levels. Besides less utilization of GSH due to less oxidative stress, it is likely that regeneration of GSH increases as more precursors of GSH will become available. Conclusions and opportunities for future investigations Erythrocytes have a distinct metabolic pattern during aging. This physiological aging is characterized by decreased enzyme activity of almost all enzymes related to the gly- colysis, Luebering-Rapoport shunt and PPP resulting in decreased ATP, 2,3DPG and GSH levels. Aging during storage shows a slightly different pattern. In non-alkaline additive solutions ATP levels also decline, but 2,3-DPG levels are almost completely depleted within two weeks. In alkaline additive solutions ATP and 2,3-DPG levels can be main- tained for a longer period. PPP activity is also dependent on the additive solution used and can be either stable during storage or increased due to increased oxidative stress. Multiple studies have been focusing on preventing the storage lesion, but normalizing one pathway always seemed to be at expense of another. Besides all the different fac- torsmentioned abovewe have to consider that not only environmental factors influence metabolic fluxes in cells, there is also a genetic component with a significant effect on the different pathways. It is seen in twin studies that a donor specific variability exists for at least GSH, GSSH and ATP levels of 79%, 60% and 53-64% respectively 59–61 . Remarkably, metabolic recovery of this storage lesion is only superficially investigated. One of the few aspects known is that ATP and 2,3-DPG levels are normalized within 4 5