Effects of hyperglycemia on red blood cell storage lesion in transfusion medicine
Red blood cell (RBC) transfusions are an important component of critical healthcare. RBCs can be donated, processed, and stored in a blood bank for future transfusion. A review of RBC storage development, as well as RBC storage lesion, is presented here. Whole blood is collected into an anticoagulant-nutrient solution such as citrate phosphate dextrose (CPD). The RBCs separated from the plasma and platelets, are then added into an additive solution, such as AS-1, which supports the nutrient needs of the RBCs in storage. The glucose concentrations in CPD and AS-1 are 129 mM and 111 mM, respectively. Thus, the glucose level in this system (estimated > 40 mM) is much higher than the healthy glucose level in vivo (4-6 mM). This dissertation hypothesizes that the hyperglycemic conditions in the current storage system result in some changes in RBCs and thereby have adverse effects on vascular function.In addition to the primary function of oxygen delivery, RBCs can function as a regulator of vascular tone. It is known that adenosine triphosphate (ATP) is released from intact RBCs in response to several stimuli and further stimulates nitric oxide (NO) production in the endothelium lining the blood vessels. This NO functions to relax the smooth muscle cells surrounding circulatory vessels, thereby increasing blood flow and oxygen delivery to the tissues. In order to investigate the effects of hyperglycemia, RBCs were processed and stored in hyperglycemic and normoglycemic conditions. The vascular function and other properties of these cells were then studied.In an in vitro microflow system, the RBCs stored in hyperglycemic conditions resulted in significantly less RBC-derived ATP for 4 weeks than the RBCs in normoglycemic conditions. During the same storage duration, microfluidic technologies enabled measurements of endothelium-derived NO that was stimulated by the ATP release from the stored RBCs. In comparison to normoglycemic solutions, the NO release decreased by more than 25% in the presence of the RBCs stored in the hyperglycemic conditions. Control experiments using inhibitors of ATP release from the RBCs, or ATP binding to the endothelium, strongly suggest that the decreased NO release by the endothelium is directly related to the ability of the stored RBCs to release ATP. Furthermore, the mechanisms behind the effect of hyperglycemia on the ability of RBCs to release ATP were investigated and discussed. It was found that an osmotic imbalance was formed in RBCs in hyperglycemic conditions, which thereby reversibly impaired the ATP release from RBCs. In addition, longer hyperglycemic storage resulted in sorbitol accumulation within RBCs and cell membrane damage in terms of lipid peroxidation, which irreversibly impaired ability of the RBCs to release ATP. Therefore, the transfusion of those stored RBCs would result in inappropriate vasodilation, less blood flow, and insufficient oxygen delivery, which are often associated with post-transfusion complications. If the RBCs could be stored and maintained in normoglycemic conditions, it may be possible to reduce these complications to some extent and hopefully improve RBC transfusion efficacy.
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- In Collections
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Electronic Theses & Dissertations
- Copyright Status
- In Copyright
- Material Type
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Theses
- Authors
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Wang, Yimeng
- Thesis Advisors
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Spence, Dana
- Committee Members
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Bruening, Merlin
Huang, Xuefei
Hrinczenko, Borys
- Date Published
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2013
- Program of Study
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Chemistry - Doctor of Philosophy
- Degree Level
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Doctoral
- Language
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English
- Pages
- xix, 188 pages
- ISBN
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9781303636844
1303636840
- Permalink
- https://doi.org/doi:10.25335/kwsf-wr39