Sanne de Bruin

134 Chapter 5 in healthy volunteers and surgical patients 62,63 . Depending on the additive solution, ATP levels restore almost completely from 35 days of storage to initial levels at the start of storage. This process takes four hours to seven days after transfusion depending on the additive solution 62 . ATP levels of donor erythrocytes recover fastest after storage in CPDA-1 and slowest after storage in AS-1 and AS-3 62 . Another study showed a restoration of ATP levels in SAGM stored RCCs within 12 hours. However, this was studied in 14 days stored blood, in which ATP levels were not completely depleted 63 . The mechanism of regaining ATP levels is yet unclear, although multiple explanations have been postu- lated. In the circulation there is plenty of substrate to fuel the glycolysis. Furthermore, the pH in the bloodstream is higher which results in increased PFK activity. Luebering-Rapoport shunt As mentioned above, 2,3-DPG is almost completely depleted after two weeks of stor- age in most commonly used additive solutions, such as SAGM. Several studies have been performed to investigate the regeneration of this metabolite after transfusion. In surgical patients 2,3-DPG levels were compared between patients transfused with stored allogenic RCCs and patients transfused with autologous salvaged blood. In the first group, significantly lower 2,3-DPG levels were observed. These 2,3-DPG levels did increase over time, but were not yet normalized at day three after transfusion 64 . In a second study patients undergoing gynaecological surgery were transfused with RCC stored for 10-14 days of storage. This study showed that 2,3-DPG levels in the donor RCCs regenerate to normal levels within 36-48 hours. Moreover, in a study performed on healthy volunteers 2,3-DPG levels restored almost completely within 72 hours to up to 95% of the initial 2,3-DPG level 62 . The clinical relevance of 2,3-DPG has been shown in humans and in several animal models 66–69 . Different experiments on rats showed that RCCs with higher 2,3-DPG con- centration resulted in better oxygenation of peripheral tissues 66–68 . This does not imply that higher 2,3-DPG levels always lead to better oxygenation of tissues. An animal model showed that too high 2,3-DPG levels impair the oxygen uptake in the lungs which in the end results in decreased systemic oxygenation 70 . The effect of 2,3-DPG depletion in transfused RCCs is different in healthy volunteers and critically ill patients. A study performed on healthy volunteers showed no difference in oxygenation of the brain and thenar eminence muscle comparing a 7 days stored transfusion with a 42 days stored RCC 71 . This is not surprising, since in healthy volun- teers no oxygenation deficit exists in contrast to critically ill patients. Furthermore, healthy volunteers have adequate compensationmechanisms to cope with a decreased