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Plasma sodium concentration is normally held within a narrow range. It may however vary greatly under pathophysiological conditions. Changes in osmolality lead to either swelling or shrinkage of red blood cells (RBCs). Here we investigated the influence of suspension osmolality on biophysical properties of RBCs and their ability to perfuse an artificial microvascular network (AMVN). Blood was drawn from healthy volunteers. RBC deformability was measured by osmotic gradient ektacytometry over a continuous range of osmolalities. Packed RBCs were suspended in NaCl solutions (0.45, 0.6, 0.9, 1.2, and 1.5 g/dL), resulting in supernatant osmolalities of 179 ± 4, 213 ± 1, 283 ± 2, 354 ± 3, and 423 ± 5 mOsm/kg H2O. Mean corpuscular volume (MCV) and mean corpuscular hemoglobin concentration (MCHC) were determined using centrifuged microhematocrit. RBC suspensions at constant cell numbers were used to measure viscosity at shear rates ranging from 0.11 to 69.5s(-1) and the perfusion rate of the AMVN. MCV was inversely and MCHC directly proportional to osmolality. RBC deformability was maximized at isosmotic conditions (290 mOsm/kg H2O) and markedly decreased by either hypo- or hyperosmolality. The optimum osmolality for RBC suspension viscosity was shifted toward hyperosmolality, while lower osmolalities increased suspension viscosity exponentially. However, the AMVN perfusion rate was maximized at 290 mOsm/kg H2O and changed by less than 10% over a wide range of osmolalities. These findings contribute to the basic understanding of blood flow in health and disease and may have significant implications for the management of osmotic homeostasis in clinical practice., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Previous computational studies have suggested that the capillary blood flow oscillations frequently observed in vivo can originate spontaneously from the non-linear rheological properties of blood, without any regulatory input. Testing this hypothesis definitively in experiments involving real microvasculature has been difficult because in vivo the blood flow in capillaries is always actively controlled by the host. The objective of this study was to test the hypothesis experimentally and to investigate the relative contribution of different blood cells to the capillary blood flow dynamics under static boundary conditions and in complete isolation from the active regulatory mechanisms mediated by the blood vessels in vivo. To accomplish this objective, we passed whole blood and re-constituted blood samples (purified red blood cells suspended in buffer or in autologous plasma) through an artificial microvascular network (AMVN) comprising completely inert, microfabricated vessels with the architecture inspired by the real microvasculature. We found that the flow of blood in capillaries of the AMVN indeed oscillates with characteristic frequencies in the range of 0-0.6 Hz, which is in a very good agreement with previous computational studies and in vivo observations. We also found that the traffic of leukocytes through the network (typically neglected in computational modeling) plays an important role in generating the oscillations. This study represents the key piece of experimental evidence in support of the hypothesis that spontaneous, self-sustained oscillations of capillary blood flow can be generated solely by the non-linear rheological properties of blood flowing through microvascular networks, and provides an insight into the mechanism of this fundamentally important microcirculatory phenomenon., (Copyright © 2012 Elsevier Inc. All rights reserved.)

We have used microfabrication technology to construct a network of microchannels, patterned after the dimensions and architecture of the mammalian microcirculation. The network is cast in transparent silicone elastomer and the channels are coated with silanated mPEG to provide lubrication. Flow of red and white blood cells through the network is readily visualized by the use of high-speed digital image acquisition. The acquired sequences of high-quality images are used to calculate hematocrits and rates of red cell movement in the microchannels. Our prototype system has significant advantages over scaled-up room-size experimental systems in that it permits experimentation with actual human blood cells. Experiments can be carried out under well-controlled conditions in a network of microchannels with precisely known dimensions using cell suspensions of defined composition. Moreover, there is no need to counteract or anticipate the host's adaptive responses that may confound live animal experiments. Notwithstanding its limitations, the current prototype demonstrates certain features characteristic of the microcirculation, such as parachute and bullet shapes of red cells deformed in capillary channels, rouleaux formation, plasma skimming, and the utilization of collateral flow pathways due to flow obstruction caused by a white cell blocking a microchannel. We present this device as a prototype scale-to-scale model of the mammalian microcirculation. Limitations of the system as well as a variety of possible applications are described.