Shear Stress-Induced Alterations in Red Blood Cell Calcium Accumulation, Microvesicle Formation, and Deformability Under Mechanical Circulatory Support Conditions
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| Publicado en: | ProQuest Dissertations and Theses (2025) |
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| 100 | 1 | |a Frey, Paige Elizabeth | |
| 245 | 1 | |a Shear Stress-Induced Alterations in Red Blood Cell Calcium Accumulation, Microvesicle Formation, and Deformability Under Mechanical Circulatory Support Conditions | |
| 260 | |b ProQuest Dissertations & Theses |c 2025 | ||
| 513 | |a Dissertation/Thesis | ||
| 520 | 3 | |a Red blood cells (RBCs) are susceptible to damage from mechanical forces, particularly shear stress, which can impair their function and lead to complications in patients supported by mechanical circulatory devices like heart pumps (LVADs & RVADs) and veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Calcium is a central focus of this work because increases in calcium within RBCs have been observed following both physiological and supraphysiological shear exposures and have been associated with decreased RBC deformability and microvesicle (MV) formation. When an RBC has impaired deformability, anemia may occur due to the inability of RBCs to traverse the slits in the spleen. Erythrocyte-derived microvesicles are known to be increased in MCS patients and have been linked to thrombosis and inflammation. This work investigates the effects of shear stress on RBC intracellular calcium accumulation, MV formation, and deformability under conditions relevant to mechanical circulatory support. In the first study, RBCs were exposed to varying shear durations (0 ms, 5 ms, and 10 ms) in microfluidic channels at a shear rate of 100,000 s-1. The microfluidic devices mimic medical devices in their high-shear stresses with short exposure times. Intracellular calcium levels, measured by flow cytometry using the calcium indicator Fluo-4, AM, showed a transient increase (160%) shortly after shear exposure that normalized within hours, suggesting an attempt to return to calcium homeostasis. Microvesicle formation did not change with exposure time in the microchannel, but decreased over time post-shear, potentially due to vesicle adhesion to cells or collection tubes, warranting further investigation. To further investigate the role of calcium in MV formation in conditions of shear stress, MV concentration was assessed in a CentriMag mock loop system, circulating bovine RBCs for 6 hours in media with and without calcium. This set-up allowed the cells to repeatedly experience the high shear areas of the CentriMag centrifugal pump at short, singular exposure times. Results demonstrated that CFSE-positive microvesicle production increased over six hours (214% in calcium media, 172% in no-calcium media) due to shear stress, independent of extracellular calcium presence. Plasma free hemoglobin (PFH) levels also rose steadily, indicating hemolysis driven primarily by mechanical stress rather than calcium-mediated processes. The third study evaluated deformability, PFH, and mean cell volume (MCV) in both bovine and human RBCs during prolonged circulation through the CentriMag pump. Deformability was relatively stable over time, but there was a detectable, significant impairment at 4.5 hours for bovine (10%) and 6 hours for human (9%). PFH levels increased consistently. Collectively, these findings emphasize how shear stress affects red blood cell integrity. Monitoring intracellular calcium, microvesicle formation, and deformability may help assess red blood cell damage in artificial organs, and this knowledge can guide the development of strategies to mitigate related complications. | |
| 653 | |a Chemical engineering | ||
| 653 | |a Biomedical engineering | ||
| 653 | |a Cellular biology | ||
| 653 | |a Engineering | ||
| 653 | |a Biomechanics | ||
| 773 | 0 | |t ProQuest Dissertations and Theses |g (2025) | |
| 786 | 0 | |d ProQuest |t ProQuest Dissertations & Theses Global | |
| 856 | 4 | 1 | |3 Citation/Abstract |u https://www.proquest.com/docview/3200120809/abstract/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch |
| 856 | 4 | 0 | |3 Full Text - PDF |u https://www.proquest.com/docview/3200120809/fulltextPDF/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch |