PLASMA VISCOSITY AND
Early investigators conceptualized blood as a viscous fluid, assuming that the viscosity controls its flow properties. But blood is not a fluid in the ordinary sense; it is a fluidized suspension of elastic cells. In 1972, G. B. Thurston was the first to measure the viscoelastic properties that control the pulsatile flow of blood. The viscoelasticity reflects the cumulative effects of many blood parameters such as plasma viscosity, red blood cell deformability, aggregation, and hematocrit.
Now extensive basic research on blood viscoelasticity and the factors affecting it has provided a firm foundation for the increasing interest in viscoelasticity among researchers in clinical medicine and physiology. The effects of compositional parameters such as hematocrit, certain plasma proteins, and clinically relevant control fluids like Dextran 40, have been studied. Major shifts in the viscoelasticity of blood have been found to be associated with such pathologies as myocardial infarction, peripheral vascular disease, cancer and diabetes [5,6,7].
VISCOSITY VS. VISCOELASTICITY
The most common method of determining the consistency of a flowing liquid uses the relation between shear stress and time rate of shear strain (or shear rate). If the flow is constant in time, then the ratio of shear stress to shear rate is the viscosity. When flows are changing with time, such as blood flow in the human circulation, the liquid generally demonstrates both a viscous and an elastic effect, both of which determine the stress-to-strain rate relationship. Such liquids are called viscoelastic. Blood plasma normally shows viscosity only, while whole blood is both viscous and elastic.
The viscoelasticity of blood is traceable to the elastic red blood cells, which occupy about half the volume. When the red cells are at rest they tend to aggregate and stack together in a space efficient manner. In order for blood to flow freely, the size of these aggregates must be reduced, which in turn provides some freedom of internal motion. The forces that disaggregate the cells also produce elastic deformation and orientation of the cells, causing elastic energy to be stored in the cellular microstructure of the blood. As flow proceeds, the sliding of the internal cellular structure requires a continuous input of energy, which is dissipated through viscous friction. These effects make blood a viscoelastic fluid, exhibiting both viscous and elastic properties.
Failure to either disaggregate or deform (or both) results in impaired perfusion of the capillary beds and failed tissue servicing. Since aggregation[9,10] and deformability[11,12] are key factors in the viscoelasticity of blood, the structural organization of cells that affects blood flow must be evaluated in terms of its contribution to the viscoelastic properties of blood, which in vivo determine the pressure-to-flow relationships in the vessels.
A scan with increasing oscillatory shear rates can show influences of aggregation, disaggregation, cell orientation and cell deformation on the viscoelasticity of blood. Figure 1 shows an example of normal human blood measured at a frequency near that of the human pulse. In Region 1, the cells are in large aggregates and as the shear rate increases, the size of the aggregates diminish. In this range of shear rates, the viscoelasticity is strongly influenced by the aggregation tendency of the red blood cells. In Region 2, the cells are disaggregated and the applied forces are forcing the cells to orient. As the shear rate increases, the applied forces deform the cells. In Region 3, increasing stress deforms the cells, and if the cells have normal deformability they will form layers that slide on layers of plasma. In this region, the viscoelasticity is strongly influenced by the deformability of red blood cells. Cells with impaired deformability produce dilatant viscoelasticity marked by elevated viscosity and elasticity in the high shear rate region.
Modification of plasma such as changes in osmotic pressure, pH, concentration of fibrinogen and other plasma proteins, and clinically introduced blood volume expanders, can have major effects on blood viscoelasticity.[2,3,9,11] For example, changing the plasma composition by addition of blood volume expanders can affect aggregation and deformability of the cells, resulting in a shear rate-dependent viscoelasticity that deviates from that of normal blood. Figure 2 shows the effect of dilution of three samples of blood from the same donor from a hematocrit of 0.46 to a hematocrit of 0.31 by the addition of autogenous plasma, lactated Ringer's, and Dextran 40, providing a 50% dilution of the original plasma.
Variation in blood viscoelasticity among normals is very small. Thus, changes due to disease or surgical intervention can be readily identified, making blood viscoelasticity a useful clinical parameter. For example, the viscoelasticity of an individual's blood changes significantly as the result of cardiopulmonary bypass surgery (Figure 3).
Examination of a group of patients undergoing CPB found that the changes seen in Figure 3 are not solely due to changes in hematocrit but also may be a due to the combined effects of 1) dilution of plasma proteins by the priming solution, 2) changes in plasma viscosity and 3) the effects of the priming solution on aggregation and deformability of the red blood cells .
CRITERIA FOR MEASUREMENT OF VISCOSITY AND VISCOELASTICITY
A suitable system for the measurement of blood viscoelasticity or plasma viscosity must have several features for clinical applications:
The BioProfiler precisely measures viscosity of plasma and both the viscous and elastic properties of blood and other biofluids under controlled conditions of frequency, temperature and time. The Vilastic-3 can measure the viscosity and elasticity of blood under oscillatory flow in cylindrical tubes that mimic a range of blood vessels (1 mm to 20 micron i.d.) and in stenotic tubes and porous media, mimicking the complex geometries encountered by flowing blood in the human circulation. Blood or plasma samples as small as 0.25 ml can be measured repeatedly with reliable results and minimal user exposure to the sample. Computer controlled measurement protocols allow for ease of operation and reproducible measurement conditions. In addition to measuring the viscoelastic character of blood, the Vilastic-3 also can monitor dynamic changes in the viscoelasticity during blood or plasma clotting.
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