The storage-lesion in murine red blood cells: comparison to stored human red blood cells and applications for an animal model of transfusion efficacy

Introduction

Under storage conditions, red blood cells (RBCs) undergo significant biochemical and biomechanical changes that compromise their ability to unload oxygen to the tissues. The clinical benefit of RBC transfusions are, therefore, less than anticipated and may lead to tissue injury rather than improvement. The development of an animal model is an important step in characterizing the loss of effective oxygen availability and assessing the efficacy of transfusion therapy. The aim of this study was to determine when stored rat RBCs develop a storage-lesion similar to human RBCs near the end of their shelf life.

Methods

Human and rat RBCs were collected in CPDA-1, packed and stored at 4°C for 29 days according to Red Cross standards. ATP and 2,3 DPG concentrations were assessed in rat and human RBCs during the storage. Biomechanical changes were assessed by assaying RBC membrane deformability (RBCd) using the micropipet aspiration technique. Stored RBCs were treated with a rejuvenation solution to determine the effect on biochemical and biomechanical function.

Results

The storage-induced decline in ATP and 2,3 DPG in human RBCs were consistent with the literature. These changes, however, occurred more rapidly in rat RBCs; ATP levels after 7 days of storage declined to the same extent as human RBCs after 4 weeks (40% decrease). DPG levels in rat and human RBCs fell by 60% and 90% after 7 days of storage. By day 7 of storage the mean membrane deformability had dropped 45% (P < 0.001). RBCs exposed to the rejuvenation protocol at day 7 had ATP levels returned to baseline while the mean RBCd showed almost complete recovery to baseline levels. Significantly, 12% of the population of rejuvenated cells still showed compromised membrane deformability (i.e. membrane displacement less than 80% of baseline).

Conclusion

The biochemical data from this study suggest that rat RBCs stored for 7 days develop a storage-lesion similar to that of human RBCs stored for 29 days. Rejuvenation of RBCs improves RBCd and may be related to improved ATP levels. Using rat RBCs stored for 7 days gives researchers a valuable tool to assess blood storage and the consequences on transfusion efficacy and tissue oxygen availability.