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A microfluidic platform to study the effects of vascular architecture and oxygen gradients on sickle blood flow.

ABSTRACT: Our goal was to develop a model of the microvasculature that would allow us to quantify changes in the rheology of sickle blood as it traverses the varying vessel sizes and oxygen tensions in the microcirculation. We designed and implemented a microfluidic model of the microcirculation that comprises a branching microvascular network and physiologic oxygen gradients. We used computational modeling to determine the parameters necessary to generate stable, linear gradients in our devices. Sickle blood from six unique patients was perfused through the microvascular network and subjected to varying oxygen gradients while we observed and quantified blood flow. We found that all sickle blood samples fully occluded the microvascular network when deoxygenated, and we observed that sickle blood could cause vaso-occlusions under physiologic oxygen gradients during the microvascular transit time. The number of occlusions observed under five unique oxygen gradients varied among the patient samples, but we generally observed that the number of occlusions decreased with increasing inlet oxygen tension. The model system we have developed is a valuable tool to address fundamental questions about where in the circulation sickle-cell vaso-occlusions are most likely to occur and to test new therapies.

SUBMITTER: Lu X

PROVIDER: S-EPMC5505799 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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A microfluidic platform to study the effects of vascular architecture and oxygen gradients on sickle blood flow.

Lu Xinran X Galarneau Michelle M MM Higgins John M JM Wood David K DK

Microcirculation (New York, N.Y. : 1994) 20170701 5

Our goal was to develop a model of the microvasculature that would allow us to quantify changes in the rheology of sickle blood as it traverses the varying vessel sizes and oxygen tensions in the microcirculation. We designed and implemented a microfluidic model of the microcirculation that comprises a branching microvascular network and physiologic oxygen gradients. We used computational modeling to determine the parameters necessary to generate stable, linear gradients in our devices. Sickle b ...[more]

PMID: 28129479

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Project description: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.

Dataset Information

A microfluidic platform to study the effects of vascular architecture and oxygen gradients on sickle blood flow.

Publications

A microfluidic platform to study the effects of vascular architecture and oxygen gradients on sickle blood flow.

Similar Datasets

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