A comparison of biochemical and functional alterations of rat and human erythrocytes stored in CPDA‐1 for 29 days: implications for animal models of transfusion

Abstract

Animal models of transfusion are employed in many research areas yet little is known about the storage-related changes occurring in the blood used in these studies. This study assessed storage-related changes in red blood cell (RBC) biochemistry, function and membrane deformability in rat and human packed RBCs when stored in CPDA-1 at 4 degrees C over a 4-week period. Human blood from five volunteers and five bags of rat RBC concentrates (five donor rats per bag) were collected and stored at 4 degrees C. RBC function was assessed by post-transfusion viability and the ability to regenerate adenosine triphosphate (ATP) and 2,3-diphosphoglycerate (DPG) when treated with a rejuvenation solution. Membrane deformability was determined by a micropipette aspiration technique. ATP in rat RBCs declined more rapidly than human RBCs; after 1 week rat ATP fell to the same level as human cells after 4 weeks of storage (rat, 2.2 +/- 0.2 micromol g(-1) Hb; human, 2.5 +/- 0.3 micromol g(-1) Hb). Baseline DPG concentrations were similar in rat and human RBCs (16.2 +/- 2.3 micromol g(-1) Hb and 13.7 +/- 2.4 micromol g(-1) Hb) and declined very rapidly in both species. Human RBCs fully regenerated ATP and DPG when treated with a rejuvenation solution after 4 weeks of storage. Rat RBCs regenerated ATP but not DPG. Post-transfusion viability in rat cells was 79%, 26% and 5% after 1, 2 and 4 weeks of storage, respectively. In rats, decreased membrane deformability became significant (- 54%) after 7 days. Human RBC deformability decreased significantly by 34% after 4 weeks of storage. The rejuvenation solution restored RBC deformability to control levels in both species. Our results indicate that rat RBCs stored for 1 week in CPDA-1 develop a storage lesion similar to that of human RBCs stored for 4 weeks and underscores significant species-specific differences in the structure and metabolism of these cells.

Increased Mortality, Postoperative Morbidity, and Cost After Red Blood Cell Transfusion in Patients Having Cardiac Surgery

“…19 Transfusion of stored RBCs also has been shown to induce tissue hypoxia in rodents. 20,21 Increased red cell aggregability 22 and rigidity, 23 the diminished microvascular autoregulatory abilities of stored red cells, 20,24 and the accumulation of potentially toxic microparticles, 25 lipophosphatidylcholines, 26 or proinflammatory cytokines 27 in the storage supernatant may all contribute to tissue hypoxia and organ dysfunction in transfused patients. Alternatively, systemic inflammation, a feature of the response to transfusion of nonleukodepleted red cells, 27 is implicated in atherosclerotic plaque rupture, stroke, and acute coronary syndromes.…”

The Age of BLood Evaluation (ABLE) randomised controlled trial: description of the UK-funded arm of the international trial, the UK cost–utility analysis and secondary analyses exploring factors associated with health-related quality of life and health-care costs during the 12-month follow-up

“…Earlier studies demonstrated that old stored rat blood did not improve tissue oxygen consumption as compared with fresh RBCs. 20 By bleeding animals and replacing blood with RBC-free solutions (isovolaemic haemodilution), haemoglobin concentrations were so low that each RBC transfusion should result in increased uptake of oxygen by cells (a supply-dependent state). If RBCs worked properly in the supply-dependent state, there should be a noticeable decrease in serum lactate levels and an increase in oxygen consumption.…”

“…However, it had subsequently been shown that these observations were in part explained by low post-transfusion survival of stored rat RBCs, but the experiments demonstrate the potentially limited efficacy of stored RBCs. 20,21 In the most comprehensive animal study, Raat et al 22 compared the transfusion of 2-to 6-day-old, 2-to 3-week-old and 5-to 6-week-old human blood in a rat isovolaemic exchange model, and showed a decrease in microvascular partial pressure of oxygen in the gut with older RBCs compared with fresh and intermediate blood. However, these changes were not marked, and their clinical relevance to human disease was uncertain.…”

Loss of red cell chemokine scavenging promotes transfusion-related lung inflammation

“…It has previously been shown that rat erythrocytes stored for 1 week show storage related alterations similar to human erythrocytes stored for 4 weeks, suggesting that the RBC storage lesion occurs more rapidly in rodent erythrocytes than human erythrocytes. 26 Given these concerns and our own observations of accelerated lysis of murine RBCs beyond 14 days, we chose to transfuse murine RBCs stored for 10 days. Mice transfused with 10-day-old RBCs showed increased airspace neutrophil counts, compared with mice transfused with RBC stored for less than 1 day (2748 vs 236, P ϭ .015, Figure 3A).…”