Deoxygenation Reduces Sickle Cell Blood Flow at Arterial Oxygen Tension
Autor: | David K. Wood, John M. Higgins, Xinran Lu |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
medicine.medical_specialty Endothelium Biophysics Infarction Inflammation Anemia Sickle Cell Hematocrit 03 medical and health sciences Lab-On-A-Chip Devices Internal medicine medicine Humans Dimethylpolysiloxanes Cell adhesion medicine.diagnostic_test Chemistry Electric Conductivity Equipment Design Blood flow Oxygenation Microfluidic Analytical Techniques medicine.disease Oxygen 030104 developmental biology medicine.anatomical_structure Cell Biophysics Hemorheology Immunology Circulatory system Cardiology medicine.symptom |
Zdroj: | Biophysical Journal. 110:2751-2758 |
ISSN: | 0006-3495 |
Popis: | The majority of morbidity and mortality in sickle cell disease is caused by vaso-occlusion: circulatory obstruction leading to tissue ischemia and infarction. The consequences of vaso-occlusion are seen clinically throughout the vascular tree, from the relatively high-oxygen and high-velocity cerebral arteries to the relatively low-oxygen and low-velocity postcapillary venules. Prevailing models of vaso-occlusion propose mechanisms that are relevant only to regions of low oxygen and low velocity, leaving a wide gap in our understanding of the most important pathologic process in sickle cell disease. Progress toward understanding vaso-occlusion is further challenged by the complexity of the multiple processes thought to be involved, including, but not limited to 1) deoxygenation-dependent hemoglobin polymerization leading to impaired rheology, 2) endothelial and leukocyte activation, and 3) altered cellular adhesion. Here, we chose to focus exclusively on deoxygenation-dependent rheologic processes in an effort to quantify their contribution independent of the other processes that are likely involved in vivo. We take advantage of an experimental system that, to our knowledge, uniquely enables the study of pressure-driven blood flow in physiologic-sized tubes at physiologic hematocrit under controlled oxygenation conditions, while excluding the effects of endothelium, leukocyte activation, adhesion, inflammation, and coagulation. We find that deoxygenation-dependent rheologic processes are sufficient to increase apparent viscosity significantly, slowing blood flow velocity at arterial oxygen tension even without additional contributions from inflammation, adhesion, and endothelial and leukocyte activation. We quantify the changes in apparent viscosity and define a set of functional regimes of sickle cell blood flow personalized for each patient that may be important in further dissecting mechanisms of in vivo vaso-occlusion as well as in assessing risk of patient complications, response to transfusion, and the optimization of experimental therapies in development. |
Databáze: | OpenAIRE |
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