140 Biofluid Mechanic: he Human Circulation such as mechanical heart valves or vascular stents. The thrombus then grows with additional platelet activation and aggregation. With the coagulation of blood, the adhered platelets combine with fibrin to form thrombus or blood clots. If the throm- bus breaks apart and forms emboli that are transported downstream, they may lodge in smaller vessels and prevent blood supply to the region downstream of those sites. Should emboli lodge in the smaller vessels in the brain, neurological deficits will occur. Heart failure can occur if the emboli affect the smaller vessels in the coronary circulation, From Figure 4.19, it can be observed that with relatively high shear rates, hemo- lysis or platelet activation can occur at very short time periods, whereas with lower magnitudes of shear stress, the cells must be under the influence of shear for a longer time before activation can be anticipated. By integrating the area under the shear stress-time plots, a single parameter with units of stress x time has also been pro- posed as an activation parameter in experimental and computational studies for the prediction of platelet activation and thrombus initiation in flow past devices such as mechanical heart valves. It should also be pointed out that the experiments from which the data for these plots were generated for the activation of platelets were performed with platelet-rich plasma (without the red blood cells) in the sample fluid subjected to prespecified shear stresses for known amount of time. In reality, under normal physiological concentration, there will be four platelets and one white blood cell present for 60 red blood cells. The effect of the ted blood cells in the fluid sam- ple on the behavior of platelets is essentially ignored in these experiments in order to relate the flow-induced stresses on platelet activation, aggregation, and throm- bus development. The mechanics of thrombus initiation with circulatory implants continues to be an active area of research even today in order to provide design improvements to minimize or prevent thrombus deposition. Thrombus formation and ensuing embolic complications continues to remain as a major problem with circulatory implants such as mechanical heart valves, vascular grafts and stents, and artificial heart and circulatory assist devices. 4.2, VASCULAR MECHANICS Pulsatile blood flow in the human arterial circulation is the result of constant inter- action between the flowing blood and the arterial wall. In the analysis of the fluid mechanics of blood flow in human arteries, we need to understand the behavior of the arterial wall in addition to knowledge about the flow behavior of blood. Therefore, we will briefly review the structural components and the mechanics of the walls of blood vessels. 4.2.1 StructurAL COMPONENTS OF THE BLOOD Vessel WALL AND THEIR CONTRIBUTION TO MATERIAL BEHAVIOR ‘The arterial wall is a composite of three layers, each of which contains varying amounts of elastin, collagen, vascular smooth muscle cells, and extracellular matri- ces (Figure 4.20). The inner most layer of the artery, called the intima, consists of a single layer of endothelial cells and a very thin lamina of elastin. The role of theRheology of Blood and Vascular Mechanics 141 Composite reinforced by collagen fibers arranged ~~ in helical structures Helically arranged fiber- reinforced medial layers Bundles of collagen fibrils — External elastic lamina Elastic lamina Elastic fibrils 7, Collagen fibrils =” Ay h Smooth muscle cell ~/",/ ‘ation Internal elastic lamina —“/ ar Endothelial cell — Meat FIGURE 4.20 Schematic of the components of a healthy artery. (From Holzapfel et al., J. Elast., 61, 1, 2000. With permission from Kluwer Academic Publishers.) endothelial cells lining the inner surface of the artery is to provide a smooth wall and selective permeability to water, electrolytes, sugars, and other substances between the bloodstream and the tissues. The outer layer, the adventitia, consists of connec tive tissue that merges with the surrounding structures. The middle layer, known as the media, consists of elastin, collagen, and vascular smooth muscles embedded in an extracellular matrix. Wall diameters, thicknesses, and compositions of various blood vessels are shown in Figure 4.21. Elastin fibers are present in all the vessels except the capillaries and the venules and are very easily stretched. Collagen fibers, which form a network in both the media and the adventitia, are much stiffer than the elastin fibers. However, the collagen fibers are normally found with a degree of slackness, and, thus, their full stiffness is not apparent until after the vessels are stretched to the extent where the slackness is removed. Even though the individual components behave like linear elastic materials, the combination of taut elastin and relaxed collagen fibers results in a nonlinear behavior as illustrated in Figure 4.22. A schematic illustration of the taut elastin and unstretched collagen fibers is shown. in Figure 4.22a. A schematic of the force-deformation test for a single elastin fiber is. shown in Figure 4.22b whose elastic modulus is about 10° dyn/cm?. A similar sche- matic for the collagen fiber behavior with an elastic modulus of about 10° dyn/em? is shown in Figure 4.22c. For a combination of elastin and collagen fibers, the effect of increasing distension where the collagen fiber becomes tant and reacts to the load will result in a bilinear curve as shown in Figure 4.22d. The continuous recruitment. of more collagen fibers with increased load results in a nonlinear force-deformation. behavior as illustrated in Figure 4.22e, The function of the elastin and collagen fibers142 Biofluid Mechanics: The Human Circulation Medium Sphincter Aorta Small art. P art arteriole pre-cap. AVA bic 30 um 35 um - 20 yan 30 jum End. Ela. w ne ° eee z DROS Fb. [ Vena cava ae Venule capillary oo 8 yum ohn 6 O End, Ela. >200 jam Mus. >45 um Eib. " FIGURE4.21 The diameter, wall thickness, and components of the wall of the various blood vessels in the circulatory system. (Redrawn from Burton, A.C., Physiology and Biophysics of the Circulation, Year Book Medical Publishers, Chicago, IL, Copyright 1971, Elsevier) is to maintain a steady tension within the vessels to act against the transmural pres- sure exerted on them. On the other hand, the function of the vascular smooth muscle is to provide an active tension by means of contraction under physiological control. Thus, more smooth muscle content is observed in the smaller arteries and arterioles where vascular resistance can be controlled by the change in the radius of the ves- sel produced by the tension of the smooth muscles. ‘The elastic modulus for smooth muscles depends upon the relaxed or contracted state of the muscle. The endothelial cells act more as sensors and mediators of physiological changes and offer negligible resistance to mechanical load. 4.2.2 Materiat Bexavior oF Btoop Vessets Uniaxial extension tests can be performed in vitro on strips of arteries cut in vari- ous orientations from the artery (such as circumferential or longitudinal strips) to determine the force-deformation behavior. When biological tissues are subjected toRheology of Blood and Vascular Mechanics 143 LPDDIN ° Collagen alone ea Combined Elastin Collagen (a) Collagen - ee @ Si o ay collagen fiber Recruitment of second of Collagen collagen fiber Recruitment of first collagen fiber = ee © Collagen’ Elastin © () FIGURE 4.22 (a) Schematic of the elastin-collagen complex in an unstretched arterial wall, (b) stress-strain relationship for an elastin and (c) for a collagen fiber, (@) stress-strain behay- ior of an elastin and collagen fiber combination, and (e) behavior with additional collagen fiber recruitment with increasing load. load-deformation tests cyclically, the tests will result in a hysteresis loop. In other words, the load-deformation curve during loading will take a different path from the unloading curve, indicating an energy loss during the loading and unloading process. With repeated loading and unloading, the area under the loop will decrease rapidly at first and reach a steady state after a number of cycles. For this reason, data on the load-deformation behavior for biological tissue are obtained only after preconditioning the tissue by loading and unloading for several cycles. Figure 4.23 shows a photograph of a strip of an aorta of a pig gripped between clamps and attached to a testing apparatus. The corresponding measured stress-strain behav- ior for the specimen is also shown in the figure. Such tests performed with speci- mens with various orientations (¢.g., longitudinal or circumferential) will yield144 Biofluid Mechanics: The Human Circulation FIGURE 4.23 Images of a pig's thoracic aorta being subjected to a uniaxial test (bottom row); and the corresponding nonlinear stress~strain relationship. information about the directional dependence of the force-deformation behavior, if any, of the arterial wall. These in vitro tests should be performed in a physiological environment with controlled ionic content, moisture, temperature, and other vai ables. Figure 4.24 represents a schematic comparison of the stress-strain relatioy ship for soft tissue such as skin, and blood vessel with dry bone and steel used in engineering applications. ‘More useful information on the actual behavior of blood vessels can be obtained by performing the tests with the vessels in their natural geometry. Segments of blood vessels in their original configuration can be used in in vitro or in sifu testing under an applied transmural pressure. For in vitro testing, relatively long segments need to Blood vessel FIGURE 4.24 A comparison of stress-strain relationship for steel, bone, blood vessel, and skin.Rheology of Blood and Vascular Mechanics 145 be obtained so that making the measurements sufficiently away from the supports can eliminate “end effects.” Once again, the physiological environment needs to be maintained during the testing to obtain any meaningful data. Consideration must be given to the changing state of the smooth muscle with in vitro specimens. In the absence of stimuli, the smooth muscles tend to relax while they also stiffen after death (“rigor mortis”), When a segment of artery is cut, the length can decrease by as much as 40% of the initial length. Hence, the usual practice with in vitro testing is to mark the length of the artery before dissecting it and then stretching the segment back to its original length before performing the tests so that the mechanical tether- ing will be similar to that in vivo. Either a static pressure or a dynamic pressure pulse is applied to the arterial seg- ment in both the in vitro and in situ tests and the changes in the radius and the wall thickness are measured to determine the load-deformation behavior. The applied pressure can be measured relatively easily with sensitive pressure transducers. However, measurement of change in radius and, especially, the wall thickness is more complicated. Several techniques using strain gages, differential transformers, or electro-optical methods have been used to measure the change in the outer radius. Measurement of the change in the internal diameter and thereby the change in the wall thickness requires data from angiographic, ultrasonic, or other imaging modali- ties. In static tests, a change in radius for a corresponding change in a step pressure increase can be measured to determine the incremental modulus as described earlier. Sufficient time must be allowed before the measurement of the diameter change after the application of pressure to allow for creep effects. In dynamic tests, a sinu- soidal pressure pulse is applied and the resulting change in diameter is continuously recorded so that viscoelastic properties of the arterial segments can be determined, In vivo tests can also be performed either by surgically exposing the vessel under study and making direct measurements or by applying noninvasive imaging tech- niques and inserting a pressure transducer by catheterization to record changes in diameter and the pulse pressure, respectively. A pressure-strain modulus can be computed using the relationship given in Equation 2.46. If the wall thickness change can also be measured, a static elastic modulus can be computed from the measured data using the relationship given in Equation 2.45. On the other hand, if a continu- ous recording of the diameter changes can be obtained along with the physiological pressure pulse, the signals can be separated into harmonics by the use of the Fourier series analysis. From this, the dynamic elastic modulus values over a range of fre- quencies can be obtained. 4.2.2.1 Assumptions in the Analysis ‘The data on changes in pressure, radii, and wall thickness, obtained from in vitro or in vivo experiments, can be reduced to the elastic modulus based on the expressions derived earlier. However, it should be kept in mind that certain assumptions have been made in deriving those expressions. For example, an expression for the elastic modulus was derived based on the thin-walled elastic tube model (Equation 2.29), This expression is applicable only in cases where (/R < 0.1. As can be observed from Figure 4,20, the 1/R ratio for most blood vessels ranges from 0.105 to 0.15. Hence, the thick-walled formulation may be more appropriate in analyzing the material146 Biofluid Mechanics: The Human Circulation properties of these vessels. The other important assumptions made in the formula- tions described earlier are the homogeneity, incompressibility, and isotropic behav- ior of the material. As already discussed, blood vessels are not homogeneous and actually consist of several layers and components. Expressions for the elastic moduli derived earlier for thick-walled models include information on the Poisson's ratio. It is common to assume that blood vessels, similar to other biological soft tissue, are incompressible and, hence, one can assign a value of 0.5 for v. This is supported by the observation that volumetric strain computations of the vessel walls of excised dogs indicate that blood vessels are essentially incompressible. Due to the tethering of the blood vessels, it can be expected that the elastic modulus in the longitudi- nal direction will be larger than those in the circumferential and radial directions. Numerous studies have been reported on the computed elastic modulus in the radial, circumferential, and axial directions with the vessel generally being increasingly stiffer along those directions, respectively. 4.2.2.2 Experimental Results Mechanical properties of blood vessels were assessed in vivo by the simultaneous measurement of intraarterial pressure and the arterial diameter in dogs in the 1960s. ‘The arteries were assumed to be thin-walled and incompressible and the viscoelastic behavior of the vessel was determined by the relationship oye ae te (4.38) 1 Rath A simple viscoelastic model has been assumed in deriving the aforementioned relationship with the circumferential stress Gp, the circumferential strain Ar/R), and the rate of strain in the circumferential direction d/dt(Ar/R,). Data for various arterial segments in the systemic circulation from very young to old dogs were pre- sented in this study. The results showed that the viscous component was relatively small compared with the elastic modulus. The in vivo elastic moduli of various arterial segments from the thoracic aorta to the femoral arteries ranged from 1,953 to 34,944 Gm/em? Bergel (1961a,b) has presented data for static and dynamic elastic moduli for the blood vessels based on the thick-walled theory for a homogeneous and isotropic material. The in vitro experiments were performed on excised blood vessels from dogs with transmural pressure load of up to 240 mmHg. A nonlinear behavior char- acterized by stiffening of the vessels with increasing pressure is apparent from the static study results shown in Figure 4.25. Incremental elastic moduli determined for a dog’s aorta as well as the femoral and carotid arteries in this study are included in Table 4.4, Bergel (1961b) also performed dynamic studies by superimposing a sinusoidal variation over a static pressure of 100mmHg and measuring the diameter changes employing a photo-optical technique. The dynamic elastic moduli computed for the canine arteries at various frequencies are compared with the corresponding static val- ues (OHz) in Table 4.5 and the results show that the dynamic incremental modulus is significantly increased even at 2Hz compared with the corresponding static values.Rheology of Blood and Vascular Mechanics 147 25 -— 20 10 Egg (dyn/cm? x 108) 20 40 60 80 100 120 140 160 180 200 220 240 Pressure (mmHg) FIGURE 4.25 Incremental static elastic modulus as a function of transmural pressure for dog’s arteries. A, Thoracic aorta; 1, abdominal aorta; 0, femoral artery; @, carotid artery. (Redrawn from Bergel, D.H., J. Physiol, 156, 445, 1961. With permission from the Physiological Society.) TABLE 4.4 Incremental Static Elastic Moduli (x10° dyn/cm?) for the Arterial Wall Pressure (mmHg) Thoracic Aorta Abdominal Aorta Femoral Artery Carotid Artery 40 12016) 16+0.4 (4) 12#02) 1.040.2(7) 100 43+04(12) 8.923.5(8) 6.9#1.0(9) 6.4 1.0 (12) 160 9.9 +05 (6) 12.4*22(4) 12.1#24(6) — 12.222.7(7) 220 18.22.85) 18.0#5.5(3) 204244(6) — 12.221.5(7) Source: From Bergel, D.H., J. Physiol. 156, 445, 1961. With permission from the Physiological Society, ‘Note: Figures in parentheses refer to the number of specimens in the experiments. At higher frequencies, the dynamic modulus does not show further changes. The dynamic elastic moduli computed at mean arterial pressures ranging from 87 to 130mmLlg and pulse frequencies ranging from 1.1 to 2.8Hz in the dog arteries in vivo showed a monotonic increase from the thoracic aorta to the femoral arteries. The vis- cous modulus ranged from 9% to 12% of the corresponding dynamic modulus. Effect of age on the viscoelastic properties of the human arterial wall have also been inves- tigated and the results showed that the viscous component of the elastic modulus was148 Biofluid Mechanics: The Human Circulation TABLE 4.5, The Dynamic Elastic Moduli («10° dyn/cm?) for the Canine Arteries at Various Frequencies Vessel/Frequency OHz 2Hz Siz 18Hz ‘Thoracic aorta 4.44040(10) 4.7#0.42(10) 4.9#0.45(10) 530.804) Abdominal aorta, -9.2#0.94(7) 10.9 0.88(7) 11.0#0.82(7) 12.20.46 (4) Femoral artery 9.041.15(5) 120£081(5) 12.00.8215) 10.6 + 1.395) Carotid artery 6.9£0.48(6) 11.04 1.00(6) —_11.3£0.99(6) 11.5 + 1.036) Source: From Bergel, D.H., J. Physiol. 156, 458, 1961. With permission from the Physiological Society. Note: Figures in parenthesis show the number of specimens used in the experiments. larger in the femoral arteries and can be attributed to higher muscular content in the wall, In the “young” group, the wall stiffness was observed to increase toward the peripheral vessels and in the “old” group, the opposite trend was observed. Such stud- ies indicate the presence of regional variation in the mechanical properties of arter- ies. Studies have also been reported on the anisotropic behavior of the arterial wall. Mean values for the incremental moduli in the radial, circumferential, and longitudinal directions of 5,480, 7,510, and 10,100 Gm/cm*, respectively, at a mean arterial pressure of 154cm HO have been reported from data obtained in vivo in dogs. ‘These studies also showed that the elastic moduli increased with increased mean arterial pressure, Moreover, the longitudinal elastic modulus measured on the same vessels in vitro showed a decrease after the removal of tethering of the vessels in situ. ‘The viscoelastic behavior of arteries is usually assessed by experiments on speci- mens obtained from healthy animals of various species and the results obtained have suggested an anisotropic, nonlinear stress-strain relationship under a transmural load from 0 to about 240mmLHg. It can be anticipated that vascular disease would alter the material behavior. Common vascular diseases in humans include atherosclerosis, high blood pressure (hypertension), and diabetes. Atherosclerosis is the formation of plaques within the artery wall and lumen and is associated with the accumulation of cholesterol combined with LDL that dissolve in plasma. The formation and growth of these lesions and their relationship with the local flow dynamics are further described in Chapter 6. In brief, early atheroma results from abnormal deposition of LDL-cholesterol within the intima, followed by a cellular response, composed of macrophages, lymphocytes and proliferating vascular smooth muscles. Collagen and elastin fibers eventually replace the cellular constituents, resulting in a changing histological picture with the lesion development. Initially, the arteries respond by remodeling or thinning of the media in order to accommodate the expanding lesion within the arterial wall in order to maintain the lumen cross section for blood flow. With further development of the plaque and as the contents become calcified, the plaques protrude into the lumen and begin occluding the cross section available for blood flow. It can be anticipated that the arterial wall material property is continually altered with the various stages of lesion development and several studies have been reported on the nature of such alterations.Rheology of Blood and Vascular Mechanics 149 ‘The arterial wall also responds to increased blood pressure by the reorganization and thickening (hypertrophy) of the medial wall in the artery. The wall thickening will result in the circumferential stress due to the transmural blood pressure returning to normal levels. Diabetes also affects the material behavior of the arterial wall and stud- ies on the alterations in arterial wall material behavior with these diseases continue to be the subject of ongoing research. ‘The interaction between stress and strain for an elastic material is the constitutive relationship describing the behavior of the material under external loading. In order to mathematically describe the material behavior for nonlinear material such as blood vessels, exponential, polynomial, or logarithmic relationships between stress and strain have been generally employed. In developing mathematical relationships for nonlinear and anisotropic materials, it is convenient to describe the material behavior in the form of a strain energy function (work done on the material in the deformation process) and to express the relationship in terms of material constants. A best curve fit of the force-deformation experimental data is employed for determining the material constants for the mathematical relationship being employed. Further details on such material behavior descriptions for biological soft tissues including blood vessels can be found in Fung (1981) and other similar more recent publications 4.2.3 ResiDUAL Stress ON BLoop VeEssELs Inengineering materials, a component that is not subjected to an external load will not have any deformation and no internal stresses will develop in the material. The arter- ies are subject to external loads through the transmural blood pressure and, hence, using the same analogy as for general engineering materials, it can be expected that arteries will be stress-free at zero transmural load. In the last couple of decades, sev- eral studies have demonstrated that the arterial wall tissue is not stress-free at zero transmural loads. This fact can be demonstrated as follows. A small segment of an artery is excised into a ring-shaped element and, subsequently, a radial cut is made on the ring-shaped segment. Should the artery be stress-free, the artery will main- tain its circular shape even after the radial cut. However, it has been demonstrated that the arterial segment opens to a sector (a horseshoe shape) within a few minutes after the longitudinal cut as schematically shown in Figure 4.26 with the arterial wall Radial cut Ring-shaped segment _Sector-shaped segment: Qhearing angle FIGURE 4.26 Schematic of a ring-shaped arterial segment and the open sector (horseshoe- shaped) stress-free state of the segment after a radial cut.150 Biofluid Mechanics: The Human Circulation Simm FIGURE 4.27 A photograph of an excised ring-shaped pig’s femoral arterial segment and the open-sector-shaped stress-free state of the artery with an additional radial cut. being stress-free in this open segment, The artery is assumed to be stress-free in the sector-shaped configuration because an additional radial cut will result in two pieces that do not result in noticeable additional strains or change in shape. A photograph. of an excised pig’s femoral artery in the ring-shaped configuration and in the sector- shaped stress-free state after a radial cut is shown in Figure 4.27. Itis evident, then, that the ring-shaped arterial segment is subjected to a prestress (or residual stress) even with no load (zero transmural pressure). The magnitude of the prestress has been generally described in terms of the opening angle of the sector shape as shown in Figure 4.26. Studies have demonstrated that the residual stress is a function of the anatomical location of the arterial segment (e.g., carotid artery versus femoral artery), and the species from which the segments are obtained. The opening angle also varies depending upon the location of the radial cut of the ring-shaped segment. By measuring the circumferential lengths of the intimal and adventitial boundaries in the uncut (ring-shaped) configuration and the corresponding lengths in the open sector configuration, the residual strains at zero load can be computed and have been shown to be compressive in the intimal layer and tensile in the adventitial layer. The computed residual stress with an assumed elastic modulus demonstrates, that the magnitudes of the residual stress are about 10% of the estimated circumfer- ential stress in the arterial wall under physiological transmural load. Under normal physiological loading neglecting the residual stress, it has been shown that circum- ferential stress is generally larger in the intimal border and decreases toward theRheology of Blood and Vascular Mechanics 151 adventitial border. Thus, the inclusion of a residual stress that is compressive in the intimal border and tensile in the adventitial border will result in a circumferential stress distribution across the arterial wall thickness which is more uniform under physiological loading. The presence of residual strain and stress has been implicated in the remodeling of the arterial wall. Finite element studies indicate that the distri- bution of the circumferential stress throughout the wall thickness is more uniform if the residual strain effect is included in the analysis. 4.2.4 MATERIAL CHARACTERIZATION OF CARDIAC MUSCLE ‘As was described in Chapter 3, the cardiac muscles constantly contract and relax in order to develop blood pressure and maintain adequate circulation to the various organs in the body. The basic structure of the cardiac muscle is a fiber that is arranged in columns that are roughly cylindrical in shape with a diameter of 10-20pm and a length of 50-100 pm. The fibers are oriented nearly vertically in the inner (endocar- dium) and outer (epicardium) layers of the muscle. The fiber orientation undergoes a gradual change through the myocardium such that the fibers in the middle third of the wall thickness are oriented circumferentially. Individual muscle fibers are surrounded by a surface-limiting membrane called the sarcolemma. Within the sar colemma, each fiber contains rodlike structures called the fibrils. The fibrils run the Iength of the fiber and contain serially repeating structures called the sarcomeres. Mitochondria are interspersed within the fibrils while the sarcotubular system sur rounds the fibrils and connects with the sarcolemma, The sarcomeres are the funda- mental functional units of cardiac contraction, In order to describe the behavior of cardiac muscles, both the passive clastic char- acteristics (during the diastolic phase) and the active contractile properties (during the early systolic phase) of the cardiac muscle need to be analyzed. The cardiac muscles are at least orthotropic with the force-deformation behavior being stiffer along the direction of the fibers compared with that in the transverse direction. Since the fiber orientation gradually changes along the thickness of the muscle, passive elastic defor- mation tests are usually performed on strips of papillary muscle since the fibers are oriented along the longitudinal direction in these muscles. Just as with other biologi- cal soft tissue, the passive stress-strain behavior of cardiac muscles is also nonlinear and an exponential stress-strain relationship is generally employed to describe the theological properties of the cardiac muscle. The contractile properties of the cardiac muscle (and skeletal muscle) are generally described using the force-velocity relation- ship that is typically obtained using the following steps. Strips of isolated papillary muscles are stretched with a preload and temporarily fixed at this length. An after load is then attached in this configuration and the muscle is stimulated. The peak velocity of contraction for the given total load (preload and after load) is measured as the muscle contracts under the stimulation, By varying the initial length of contraction as well as the preload, a family of force-velocity curves is obtained. In the case of cardiac muscle, the data extrapolated to obtain the velocity at no load from the set of curves converge toa single point referred to as the maximum velocity of shortening. The passive elastic properties as well as the maximum velocity of shortening can be altered if the cardia muscles are diseased due to myocardial infarction or cardiomyopathy.152 Biofluid Mechanics: The Human Circulation 4.3 SUMMARY In this chapter, the rheological behavior of blood was considered. The basic rela- tionships for viscometry were developed and the application of viscometry to measure the viscosity of blood and plasma was discussed. The importance of understanding the rheological behavior of blood and its changes with diseased states was briefly discussed. A study of the arterial wall material behavior is important for a basic understanding of the physiology of blood vessels. The arter- ies serve as a pressure reservoir in the circulation. As blood is ejected from the left ventricle during systole, the vessel walls distend as the arterial pressure rises. Later, during diastole, the passive arterial wall tension maintains a force to drive the blood through the peripheral capillaries. Assessment of mechanical properties of the blood vessels in various segments of the peripheral circulation is important in the understanding of the propagation of pressure pulses and the pressure—flow relationship in the circulation under normal and diseased states. It is also impor- tant to understand the interaction between blood flowing through the lumen and the vessel wall. Knowledge of the behavior of the normal artery will also be help- ful in early detection of any diseases of the blood vessels such as atherosclerosis. Study of the material characterization of the cardiac muscles is also important in our understanding of normal physiological behavior and various alterations that occur with the onset of diseases. PROBLEMS 4.1 Derive the relationship for the torque developed in a Couette viscometer (Equation 4.4). A typical Couette viscometer with a 4.0cm inner diameter, 4.2cm outer diameter, and 6cm height is used to measure the viscosity of blood. If the angular velocity is 50rpm, compute the torque required to rotate the outer cylinder. Also plot the distribution of the rate of shear between the inner and the outer cylinder. Use a whole blood viscosity of 3.50P. 4.2. For a typical red blood cell, the intracellular fluid volume is 87 pm? and the surface area of the cell is 163 pm?. If the red blood cell had a spherical shape with the same intracellular fluid volume, compute the surface area for the same. What is the advantage of the biconcave shape for the red blood cell? 4.3. Plot apparent viscosity as a function of shear rate for the relationship given by Equation 4.6 for a range of shear rates from 1 to 500s“. Compute the apparent viscosity of blood at a rate of shear of 230 s-!. Use a plasma viscos- ity of 1.2¢P, 4.4 Fora normal hematocrit of 43% and fibrinogen concentration of 0.3 g/100mL, compute the yield stress for blood employing the empirical formulae given in Equation 4.8. In a capillary with a diameter of 5m and a length of 1 mm,