Rheologic and morphometric parameters of the microcirculation bed in the rabbit ear following local ischemia

Microvessels of the rabbit ear chamber and blood samples drawn from the internal ear vein were studied after 30-min ischemia. Total microvascular bed area augmented by 16%, total microvascular bed length increased by 9% and mean microvascular diameter increased by 6.7%. One hour after the onset of ischemia it is only the diameter that remains augmented. In the control experimental series apparent viscosity of the blood flowing from the ischemic area did not correlate with the degree of vascularization, negative relation with vessel length (p = --0.461) and positive relation with the diameter (p = 0.799) being revealed. After ischemia only the viscosity-diameter relation remained significant (p = 0.466). The correlation matrix 10 X 10 which reflected the connection between other parameters characterizing specificity of blood supply regulation is given.     

Effects of flowing RBCs on adhesion of a circulating tumor cell in microvessels

Adhesion of circulating tumor cells (CTCs) to the microvessel wall largely depends on the blood hydrodynamic conditions, one of which is the blood viscosity. Since blood is a non-Newtonian fluid, whose viscosity increases with hematocrit, in the microvessels at low shear rate. In this study, the effects of hematocrit, vessel size, flow rate and red blood cell (RBC) aggregation on adhesion of a CTC in the microvessels were numerically investigated using dissipative particle dynamics. The membrane of cells was represented by a spring-based network connected by elastic springs to characterize its deformation. RBC aggregation was modeled by a Morse potential function based on depletion-mediated assumption, and the adhesion of the CTC to the vessel wall was achieved by the interactions between receptors and ligands at the CTC and those at the endothelial cells forming the vessel wall. The results demonstrated that in the microvessel of \(15\,\upmu \hbox {m}\) diameter, the CTC has an increasing probability of adhesion with the hematocrit due to a growing wall-directed force, resulting in a larger number of receptor–ligand bonds formed on the cell surface. However, with the increase in microvessel size, an enhanced lift force at higher hematocrit detaches the initial adherent CTC quickly. If the microvessel is comparable to the CTC in diameter, CTC adhesion is independent of Hct. In addition, the velocity of CTC is larger than the average blood flow velocity in smaller microvessels and the relative velocity of CTC decreases with the increase in microvessel size. An increased blood flow resistance in the presence of CTC was also found. Moreover, it was found that the large deformation induced by high flow rate and the presence of aggregation promote the adhesion of CTC.     

Early recovery of microvascular perfusion induced by t-PA in combination with abciximab or eptifibatide during postischemic reperfusion

Background  

GPIIb/IIIa inhibitors abciximab and eptifibatide have been shown to inhibit platelet aggregation in ischemic heart disease. Our aim was to test the efficacy of abiciximab (Reo Pro) or eptifibatide (Integrilin) alone or in combination with plasminogen activator (t-PA) in an experimental model of ischemia reperfusion (I/R) in hamster cheek pouch microcirculation visualized by fluorescence microscopy. Hamsters were treated with saline, or abiciximab or eptifibatide or these drugs combined with t-PA infused intravenously 10 minutes before ischemia and through reperfusion. We measured the microvessel diameter changes, the arteriolar red blood cell (RBC) velocity, the increase in permeability, the perfused capillary length (PCL), and the platelet and leukocyte adhesion on microvessels.     

Mechanical behavior of the erythrocyte in microvessel stenosis

The passage of red blood cells (RBCs) through capillaries is essential for human blood microcirculation. This study used a moving mesh technology that incorporated leader-follower pairs to simulate the fluid-structure and structure-structure interactions between the RBC and a microvessel stenosis. The numerical model consisted of plasma, cytoplasm, the erythrocyte membrane, and the microvessel stenosis. Computational results showed that the rheology of the RBC is affected by the Reynolds number of the plasma flow as well as the surface-to-volume ratio of the erythrocyte. At a constant inlet flow rate, an increased plasma viscosity will improve the transit of the RBC through the microvessel stenosis. For the above reasons, we consider that the decreased hemorheology in microvessels in a pathological state may primarily be attributed to an increase in the number of white blood cells. This leads to the aggregation of RBCs and a change in the blood flow structure. The present fundamental study of hemorheology aimed at providing theoretical guidelines for clinical hemorheology.     

Alteration of blood hemorheologic properties during cerebral ischemia and reperfusion in rats

The cerebral ischemia and reperfusion rat model was employed in this experiment to study the rheological properties (i.e. viscosity, hematocrit, red blood cell deformability and thixotropic properties) of whole blood. The results of this study show that a significant relation exists between the duration of cerebral ischemia and reperfusion and the viscosity, hematocrit and thixotropic parameters of whole blood, but there is no significant influence on the deformability of RBC. Blood viscosity values declined gradually throughout the ischemia period, e.g., after 1h of ischemia, the values of whole blood viscosity under high, middle and low shear rates were 44, 28 and 23% lower than normal, respectively. Whereas after 1h of reperfusion, the values of viscosity increased rapidly to values 160, 57 and 41% higher than normal under the high, middle and low levels of shear rate, while the viscosity values after 12h of reperfusion tended to return to normal values. The values of hematocrit H and thixotropic parameter tau(0) and mu also gradually declined with the increase in the duration of ischemia, but increased significantly after 1h of reperfusion. The values of H, tau(0) and mu after 1h of reperfusion are significantly greater than that in the period of cerebral ischemia, the value of H, tau(0) is also higher than normal. With the increase in reperfusion time, H, tau(0) gradually returned to normal level, at the same time, mu also decreased.     

Red Blood Cells: Centerpiece in the Evolution of the Vertebrate Circulatory System

All vertebrates except cold-water ice fish transport oxygenvia hemoglobin packaged in red blood cells (RBCs). VertebrateRBCs vary in size by thirtyfold. Differences in RBC size havebeen known for over a century, but the functional significanceof RBC size remains unknown. One hypothesis is that large RBCsare a primitive character. Agnathans have larger RBCs than domammals. However, the largest RBCs are found in urodele amphibianswhich is inconsistent with the hypothesis that large RBCs areprimitive. Another possibility is that small RBCs increase bloodoxygen transport capacity. Blood hemoglobin concentration ([Hb])and mean RBC hemoglobin concentration (MCHC) increase from Agnathato birds and mammals. However, the changes in [Hb] and MCHCdo not parallel changes in RBC size. In addition, RBC size doesnot affect blood viscosity. Thus, there is no clear link betweenRBC size and oxygen transport capacity. We hypothesize thatRBC size attends changes in capillary diameter. This hypothesisis based on the following observations. First, RBC width averages25% larger than capillary diameter which insures cell deformationduring capillary flow. Functionally, RBC deformation minimizesdiffusion limitations to gas exchange. Second, smaller capillariesare associated with increased potential for diffusive gas exchange.However, smaller capillaries result in higher resistances toblood flow which requires higher blood pressures. We proposethat the large capillary diameters and large RBCs in urodelesreflect the evolutionary development of a pulmonary vascularsupply. The large capillaries reduced systemic vascular resistancesenabling a single ventricular heart to supply blood to two vascularcircuits, systemic and pulmonary, without developing high pressureson the pulmonary side. The large RBCs preserved diffusive gasexchange efficiency in the large capillaries.     

Intravital morphometric characteristics of the pial network of associative and projection regions during contralateral cooling of the cat cortex

Morphometric parameters of pial vessel bed in somatosensory (region 1) and parietal (middle third of f. supra-sylvii) zones of the right brain hemisphere were determined using automatic image analysis in acute experiments on normal cats and during 1-hour cooling blockade of the same regions in the left hemisphere. In normal conditions values of pial vessel bed area were higher in the somatosensory zone, with the vessels 16-50 micron in diameter prevailing. In the parietal zone vessels with a diameter of 5-15 micron prevailed. Primary vessel constriction was observed during cooling. Later the tendency to prolonged increase of specific bed length in the parietal zone, particularly during cooling of the symmetrical region, was noted. The data obtained reveal structural and functional peculiarities of pial system in associative and projection cortical zones and their significance in compensatory-restoration process after injury.     

Erythrocyte deformability and segmental pulmonary vascular resistance: osmolarity and heat treatment

The site and nature of change in resistance to blood flow in canine left lung lobe preparation after changes in blood viscosity were assessed by using the arterial and venous occlusion (AVO) technique and the vascular pressure-flow relationship. Blood viscosity was changed by erythrocyte (RBC) shrinkage and swelling with hypertonic and hypotonic NaCl solutions and by RBC membrane rigidification with heat treatment (49 degrees C for 1 h). The results show that although all three methods of changing blood viscosity increased the pulmonary vascular resistance (PVR) by 15-50%, the site and nature of the change in PVR were different in each case. The AVO data showed that the increase in PVR with heat treatment of RBC's was due entirely (100%) to increased resistance of the middle microvascular segment, whereas deviation from normal osmolarity potentiated the resistance in arterial, middle, and venous segments. By examining the effect of osmolarity in plasma-perfused lobes, it was possible to separate the increase in PVR due to changes in RBC deformability from those due to other factors. The increase in arterial and venous resistances with hypertonic solution was attributed in part (approximately 50%) to factors other than RBC's; however, the increase in middle resistance was entirely due to RBC crenation. The increase in arterial and venous resistances with hypotonic solutions was small and was apparently caused by factors other than RBC swelling, whereas the increase in middle resistance was partially (approximately 50%) due to RBC swelling and partially to other factors (e.g., endothelial cell hydration).(ABSTRACT TRUNCATED AT 250 WORDS)     

Neutrophil retention in model capillaries: deformability, geometry, and hydrodynamic forces

The initial retention of neutrophils within the pulmonary microvascular bed occurs in both physiological and pathological states, yet the factors responsible for this retention are poorly understood. Because the diameter of the neutrophil is approximately 7.03 micron and the mean pulmonary capillary diameter is 5.5 micron, we postulated that geometric constraints imposed by the microvascular bed, the deformability of the neutrophil, and the hydrodynamic characteristics of blood were important determinants of neutrophil retention. We used a filtration system wherein 111In-labeled human neutrophils (111In-N) suspended in a serum-containing buffer were passed through Nuclepore filters of known pore size. Compared with 99mTc-labeled erythrocytes (99mTc-RBC), the passage of 111In-N was delayed and a higher percentage was retained within the filter. Because the neutrophil and RBC are approximately equal in diameter, the deformability of the neutrophil must be less than that of RBC. As the flow rate increased, retention in the filters decreased logarithmically from 72 +/- 5% (flow rate 0.5 ml/min) to 15 +/- 4% (10.0 ml/min). As the number of RBC in the buffer increased, neutrophil retention in 5-micron filters decreased in a linear fashion from 65 +/- 6% at hematocrit of 0 to 33 +/- 2% at hematocrit of 10. The perfusion pressure and shear stress were of critical importance, and there was a logarithmic relationship between retention and perfusion pressure or shear stress (tau), whether the increase in pressure or tau was generated by increasing flow or by increasing the hematocrit of the perfusate. As the pore size of the filter increased, the retention of neutrophils decreased in a logarithmic fashion: from 75 +/- 5% in the 3-micron filter to 4 +/- 1.3% in the 12-micron filter.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of high osmotic media on blood viscosity and red blood cell deformability

Effects of high osmotic media on the shape and deformability of RBC were examined for determining increasing factors of blood viscosity. Dog blood and Urographin (a hypertonic contrast medium) were used; the plasma osmolality was changed by Urografin suspended in blood. The viscosity was measured for normal RBC and glutaraldehyde-treated RBC suspensions with a cell volume concentration. The RBC deformability was evaluated from the difference in viscosity between the two suspensions. It was shown that normal RBC suspension increased the viscosity with increase in osmolality at high shear rate; hardened RBC suspension decreased the viscosity with increase in osmolality. It was concluded that the RBC deformability decreased with increasing osmolality.     

Technique-dependent variations in cerebral microvessel blood volumes and hematocrits in the rat.

To quantitate small parenchymal microvessel blood volumes in the brain, the distribution spaces of radiolabeled red blood cells (RBC) and serum albumin (RISA) were assessed in rats by different methods of tissue sampling and radioassay. Three minutes after intravenous administration of 55Fe-RBCs and/or 125I-RISA, the rats were decapitated. The brain was either immediately frozen within the skull and later removed (head-frozen group) or rapidly removed from the skull and then frozen (brain-frozen group). Radioactivity was measured either by liquid scintillation counting of tissue pieces, which contained pial plus large and small parenchymal microvessels, or by quantitative autoradiography (QAR) of tissue sections, which indicated small parenchymal microvessel blood only. In 12 of 15 areas, the RISA, RBC, and blood volumes determined by liquid scintillation counting of head-frozen tissue pieces were equal to or greater than those of brain-frozen tissue; this indicated less than or equal to 25% greater blood retention in pial and parenchymal microvessels with head freezing. At the parenchymal microvessel level (QAR assay), the distribution volumes of RBCs, RISA, and blood were similar with the two freezing techniques; hence with QAR either freezing procedure can be used to assess small parenchymal microvessel blood volumes.     

Action of hydroxyethyl starch on the flow properties of human erythrocyte suspensions

Hydroxyethyl starch (HES) has often been used as a plasma expander, but questions still remain concerning the mechanisms by which it produces changes in the rheological properties of blood and erythrocyte (RBC) suspensions under various flow conditions. The present investigation has shown that the dynamic viscosity of HES (232,000 and 565,000 daltons) solutions rises in a nonlinear fashion with increasing HES concentration, and for a given concentration of HES exhibits Newtonian behavior at shear rates between 0.15 to 124 sec-1. At low (less than 0.9 sec-1) shear rates the apparent viscosity of a 40% RBC suspension increases with lower concentrations of HES because of RBC aggregation. At higher concentrations of HES, increases in suspension viscosity are due to an increase in the viscosity of the continuous phase since the RBC are largely disaggregated. At high (greater than 36 sec-1) shear rates the relative viscosity (eta/eta O) of RBC suspensions slowly decreases with increasing HES concentration. At low shear rates eta/eta O increases and then decreases with increasing HES concentration. Evidence of the concentration-dependent effects of HES on RBC aggregation is provided not only by the viscometric analysis but also from measurements of erythrocyte sedimentation rate (ESR) and the zeta sedimentation ratio (ZSR). HES is a more potent aggregating agent in phosphate buffered saline (PBS) than it is in plasma. Polymer size has only a slight effect on the extent of RBC aggregation produced, but does have a significant effect on the concentration of polymer at which maximum aggregation occurs. The viscosity-corrected electrophoretic mobility of RBC in HES rises monotonically with the concentration of HES in the suspending medium. Decreases in the extent of RBC aggregation with increasing polymer concentrations probably result from an increase in the electrostatic repulsive forces between the cells.     

Characteristics of the energy of electrostatic interaction of the formed elements of blood in experimental myocardial ischemia]

The diffusion and z-potentials of red cells of the blood outflowing from the zone of myocardial ischemia through the branch of the large cardiac vein were studied during acute period of experimental myocardial infarction. This enabled one to calculate the energy of electrostatic repulsion (EER) between blood constituents and to identify the factors exerting a significant effect on this value in acute experimental myocardial infarction induced in 20 dogs by ligation of the anterior interventricular branch of the left coronary artery. It was shown that the energetic state of the double electric lesion is the leading factor in the changed EER and in manifestation of the aggregation activity by the blood constituents. It was noted that the energetic potentials of red cells of the blood collected from the zone of myocardial ischemia show a statistically significant reduction.     

Reperfusion damages to the heart in acute transitory coronary failure and their prevention with myophedrin

Experiments were made on 56 white noninbred male rats with transitory coronary insufficiency (duration of myocardial ischemia 10, 40 and 120 min, the length of subsequent reperfusion 10 and 40 min). It was discovered that there were changes in the ultrastructure of cardiocytes and vessels of the microcirculatory bed both in the area of ischemia and reperfusion and in the distant heart regions, an increase in myocardial cell and microvessel lesions during postischemic reperfusion not only in the area of ischemia but also in distant zones. In addition, a reduction was noted in the degree of ischemic and reperfusion myocardial injury during the prophylactic use of myophedrine. The mechanisms of the protective action of myophedrine in acute transitory coronary insufficiency are discussed.     

A comparative analysis of the persistence of capillary blood flow oscillations in the left and right rat kidneys

Several parameters of the nonlinear dynamics of blood flow oscillations were studied in the left and right rat kidneys in baseline conditions and a perturbed state. An intramuscular injection of aspirin in 0.9% saline (0.5 mg per 100 g body weight) was used as a perturbation factor. Capillary blood flow was measured at baseline and 50 min after the aspirin injection by laser Doppler flowmetry. The persistence of time series was estimated by the Hurst method. Baseline time series were persistent in the right kidney and nonpersistent in the left kidney. Aspirin-perturbed time series were persistent in both the right and left kidneys, but the Hurst index was significantly higher in the left kidney. The results showed that the microcirculatory bed of the right rat kidney is more stable to perturbation as compared with that of the left kidney.     

Hydrodynamic interaction between erythrocytes and leukocytes affects rheology of blood in microvessels

Hydrodynamic interaction between erythrocytes (RBC) and leukocytes (WBC) in a microvessel of size 20-40 micron, typical of a postcapillary venule, is studied using a two-dimensional computational model. The model is based on immersed boundary method, and it takes into consideration the particulate nature of blood by explicitly modeling individual blood cell, and cell deformation. Due to their highly flexible nature, RBC drift away from the wall and toward the center of a vessel creating a cell-free layer. It is shown here that the lateral motion of RBC is strongly affected in presence of a WBC, and is dependent on whether the WBC is non-adherent or firmly adhered. When the WBC is non-adherent, some RBC, depending on their initial radial locations and vessel size, may be deflected closer toward the wall, resulting in a decrease in the cell-free layer. The apparent viscosity of the whole blood containing both RBC and WBC is computed, and shown to be much higher than that containing RBC only. The increased viscosity cannot be accounted for by the contribution due to WBC only. This observation is in agreement with a previous in vivo measurement. Here we show that the additional flow resistance is due to the decrease in the cell-free layer resulting from the WBC-RBC interaction. It can be accounted for by a two-layer model of blood when the reduced values of the cell-free layer thickness are used. When the WBC is firmly adhered, RBC easily move away from the wall, and the cell-free layer is not significantly changed. In such cases, the major contribution to whole blood viscosity comes from the WBC alone. The hydrodynamic interaction between WBC and RBC, though it exists, does not contribute significantly when WBC are adhered.     

Assessment of the hemorheological profile of koala and echidna

Koala, a marsupial, and echidna, a monotreme, are mammals native to Australia. Blood viscosity (62.5–1250 s^?1), red blood cell (RBC) deformability, RBC aggregation, aggregability and surface charge, and hematological parameters were measured in blood samples from six koalas and six echidnas and compared to adult human blood. Koala had the largest RBC mean cell volume (107.7±2.6 fl) compared to echidna (81.3±2.6 fl) and humans (88.4±1.2 fl). Echidna blood exhibited the highest viscosity over the entire range of shear rates. Echidna RBC were significantly less deformable than koala RBC but more deformable than human RBC. Echidna RBC had significantly lower aggregability (i.e., aggregation in standardized dextran medium) than koala or human RBC, while aggregation in autologous plasma was similar for the three species. Erythrocyte surface charge as indexed by RBC electrophoretic mobility was similar for human and echidna cells but was 40% lower for koala RBC. Data obtained during this preliminary study indicate that koala and echidna have distinct hemorheological characteristics; investigation of these properties may reveal patterns relevant to specific behavioral and physiological features of these animals.     

Evaluation of the cerebral hemodynamic response to rhythmic handgrip.

The response of the cerebral circulation to exercise has been studied with transcranial Doppler ultrasound (TCD) because this modality provides continuous measurements of blood velocity and is well suited for the exercise environment. The use of TCD as an index of cerebral blood flow, however, requires the assumption that the diameter of the insonated vessel is constant. Here, we examine this assumption for rhythmic handgrip using a spectral index designed to measure trends in vessel flow. Nineteen normal subjects were studied during 5 min of volitional maximum rhythmic right handgrip at 1 Hz. TCD velocities from both middle arteries (left and right), blood pressure, and end-tidal PCO(2) were recorded every 10 s. A spectral weighted sum was also calculated as a flow index (FI). Averages were computed from the last 2 min of handgrip. Relative changes in velocity, FI, and pressure were calculated. The validity of FI was tested by comparing the change in diameter derived from equations relating flow and diameter. Mean blood pressure increased 23.8 +/- 17.8% (SD), and velocity increased 13.3 +/- 9.8% (left) and 9.6 +/- 8.3% (right). Although the mean change in FI was small [2.0 +/- 18. 2% (left) and 4.7 +/- 29.7% (right)], the variation was high: some subjects showed a significant increase in FI and others a significant decrease. Diameter estimates from two equations relating flow and luminal area were not significantly different. Decreases in FI were associated with estimated diameter decreases of 10%. Our data suggest that the cerebral blood flow (CBF) response to rhythmic handgrip is heterogeneous and that middle cerebral artery flow can decrease in some subjects, in agreement with prior studies using the Kety-Schmidt technique. We speculate that the velocity increase is due to sympathetically mediated vasoconstriction rather than a ubiquitous flow increase. Our data suggest that the use of ordinary TCD velocities to interpret the CBF response during exercise may be invalid.     

The influence of suspending phase viscosity on the passage of red blood cells through capillary-size micropores

Much attention has been paid to the study of blood flow in long, narrow tubes. While the influence of tube diameter and driving pressure have been examined in detail, the influence of suspending phase viscosity has generally been assumed only to affect the blood viscosity in a linearly proportional manner, hence the practice of normalizing apparent blood viscosity values by the suspending phase viscosity to give a relative viscosity (e.g., Pries et al., 1992). While this assumption is probably valid for long tubes, it apparently does not hold for blood flow in short tubes (and by extension also for flow in short or branching capillary segments in vivo) in which RBC deformation plays a more significant role. In this paper we present a series of experiments using the Cell Transit Analyzer (CTA) in which the influence of driving pressure and suspending phase viscosity on RBC passage through short, narrow tubes has been systematically evaluated. Over the range studied (1 to 10 cm water), the influence of driving pressure was found to be unremarkable, in that RBC velocity scaled directly and linearly with pressure. This finding is consistent with previous studies. However, a distinct intercept was observed in the linear relationship between RBC pore transit time and suspending phase viscosity, which presumably arises as a consequence of RBC deformation either at the pore entrance or within the pore. Two simple mathematical models for the suspending phase-viscosity/transit-time relationship were considered. The results show that making CTA measurements over a range of suspending medium viscosities is a simple and practical way to obtain additional information about RBC mechanical properties.     

Numerical Analysis of Blood Flow through COVID-19 Infected Arteries

Computational Fluid Dynamics has become relevant in the study of hemodynamics, where clinical results are challenging to obtain. This paper discusses a 2-Dimensional transient blood flow analysis through an arterial bifurcation for patients infected with the Coronavirus. The geometry considered is an arterial bifurcation with main stem diameter 3 mm and two outlets. The left outlet (smaller) has a diameter of 1.5 mm and the right outlet (larger), 2 mm. The length of the main stem, left branch and right branch are fixed at 35 mm, 20 mm and 25 mm respectively. Viscosity change that occurs in the blood leads to different parametrical changes in blood flow. The blood flow towards the smaller branch is significantly affected by the changed blood viscosity. Extended regions of high pressure and increased velocity towards the larger outlet are obtained. The Time Averaged Wall Shear Stress (TAWSS) for the corona affected artery is found to be 10.4114 Pa at a 90° angle of bifurcation as compared to 2.45002 Pa of the normal artery. For varying angles of bifurcation, an angle of 75° was found to have a maximum Time Averaged Wall Shear Stress of 2.46076 Pa and 10.42542 Pa for normal and corona affected artery, respectively.