Clinical Hemorheology and Microcirculation - Volume 14, issue 4
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Clinical Hemorheology and Microcirculation, a peer-reviewed international scientific journal, serves as an aid to understanding the flow properties of blood and the relationship to normal and abnormal physiology. The rapidly expanding science of hemorheology concerns blood, its components and the blood vessels with which blood interacts. It includes perihemorheology, i.e., the rheology of fluid and structures in the perivascular and interstitial spaces as well as the lymphatic system. The clinical aspects include pathogenesis, symptomatology and diagnostic methods, and the fields of prophylaxis and therapy in all branches of medicine and surgery, pharmacology and drug research.
The endeavour of the Editors-in-Chief and publishers of
Clinical Hemorheology and Microcirculation is to bring together contributions from those working in various fields related to blood flow all over the world. The editors of
Clinical Hemorheology and Microcirculation are from those countries in Europe, Asia, Australia and America where appreciable work in clinical hemorheology and microcirculation is being carried out. Each editor takes responsibility to decide on the acceptance of a manuscript. He is required to have the manuscript appraised by two referees and may be one of them himself. The executive editorial office, to which the manuscripts have been submitted, is responsible for rapid handling of the reviewing process.
Clinical Hemorheology and Microcirculation accepts original papers, brief communications, mini-reports and letters to the Editors-in-Chief. Review articles, providing general views and new insights into related subjects, are regularly invited by the Editors-in-Chief. Proceedings of international and national conferences on clinical hemorheology (in original form or as abstracts) complete the range of editorial features.
The following professionals and institutions will benefit most from subscribing to
Clinical Hemorheology and Microcirculation: medical practitioners in all fields including hematology, cardiology, geriatrics, angiology, surgery, obstetrics and gynecology, ophthalmology, otology, and neurology. Pharmacologists, clinical laboratories, blood transfusion centres, manufacturing firms producing diagnostic instruments, and the pharmaceutical industry will also benefit.
Important new topics will increasingly claim more pages of
Clinical Hemorheology and Microcirculation: the role of hemorheological and microcirculatory disturbances for epidemiology and prognosis, in particular regarding cardiovascular disorders, as well as its significance in the field of geriatrics. Authors and readers are invited to contact the editors for specific information or to make suggestions.
Abstract: Two circulations of material in the human body are stated in ancient literature of traditional Chinese medicine (TCM), namely Qi (vital energy) circulation and Xue (blood) circulation. Blood stasis syndrome (BSS) is one of the important syndromes in TCM. BSS is involved in many of the main diseases. The diagnostic criteria for BSS are established, covering traditional and laboratory criteria. Hemorheological abnormalities are one of them. The principle treatment of BSS is activating blood circulation to remove blood stasis (ABCRBS). The progress in the treatment of BSS by ABCRBS reveals promising clinical benefits and encouraging efficacy in hemorheological factors.
Keywords: blood stasis, blood viscosity, coagulation, hemorheology, platelet, traditional medicine
Abstract: The Diabetes Control and Complications Trial (DCCT), an NIH-sponsored study at 29 institutions in the U.S. and Canada, was designed to examine the effects of intensive management in type I diabetes. Between 1983 and 1989, 1441 patients with and without mild retinopathy (primary and secondary) were randomized into two major treatment groups, intensively and conventionally treated patients. Retinopathy, nephropathy, and neuropathy were assessed periodically in each patient. In this study, levels of fibrinogen, haptoglobin, albumin and total protein were measured and viscosity of fresh blood was simultaneously evaluated in 45 local DCCT patients. Viscosity was measured at 17 rotation rates…arranged logarithmically from .03 to 300 inverse seconds shear rate on blood adjusted to 41% hematocrit by the addition or removal of its own plasma. Blood's time-based flow properties — transient resistance and viscoelasticity — were also assessed. Blood viscosity showed the greatest elevation (10 to 19%) in the 0.08–2.0 inverse second shear rate range. Increased low shear rate blood viscosity was found to be linked to fibrinogen and hemoglobin A1c levels. In addition to steady flow blood viscosity measurement, blood's time-based flow properties were also assessed at 15 inverse seconds shear rate. Transient resistance was increased 30% in diabetes; its elevation was found to be linked to both fibrinogen level and low shear blood viscosity. Diabetic blood's viscoelasticity at this high shear rate was much less strikingly increased than its transient resistance. Viscoelastic strain energy was correlated with fibrinogen, low shear viscosity, haptoglobin, and albumin level. Interleukin-6 (IL-6), a potent stimulator of fibrinogen and haptoglobin synthesis in hepatocytes in culture, was found to be elevated in diabetes, indicating that it is the likely mediator of the observed plasma protein changes. The altered blood flow properties observed in this well-characterized group of type 1 diabetes mellitus patients may play a role in development of diabetic complications.
Keywords: diabetes mellitus, type I diabetes, blood viscosity, transient resistance
Abstract: The Diabetes Control and Complications Trial (DCCT), an NIH-sponsored study at 29 institutions in the U.S. and Canada, began in 1983 to examine the effects of intensive blood glucose management on the complications of type I diabetes. About half of the 1441 patients studied were randomized into a conventional treatment group and half into an intensive management group. About half of each treatment group had diabetes of 1–5 years duration and no retinopathy at randomization (primary) and half had diabetes of 1–15 years duration and minimal retinopathy at randomization (secondary). Hemoglobin A1c levels were regularly measured. Information about complications collected…systematically included retinal photographs, nerve conduction velocity assessment and evaluation of albuminuria and renal function. Differences in mean Hemoglobin A1c level between the intensively-treated group and the group continuing their usual treatment were sustained and substantial. Mean hemoglobin A1c levels were 1% compared to 3% above the normal range. We measured fibrinogen, haptoglobin, albumin and total protein levels of 1347 patients from April to August of 1991. Mean fibrinogen (measured both by coagulation quantification and clotting time after dilution) and haptoglobin were elevated and albumin level modestly depressed in the overall DCCT group and gender-based differences were also noted. Despite past reports linking diabetes control to plasma protein levels, no trend to normalization was found in the intensively treated group. In fact, mean haptoglobin level was modestly higher in the intensively treated compared to the conventional group. The primary and secondary prevention components had a well-defined difference in total plasma globulin, linked to marginal differences in albumin and total protein level. The globulin was higher in the secondary prevention group, who by study design manifested more microvascular changes. Intensive management of diabetes has no direct favorable effect on the levels of the major blood proteins that influence blood's flow properties.
Keywords: diabetes mellitus, type I diabetes, fibrinogen, haptoglobin, plasma albumin
Abstract: The deformability of polymorphonuclear leukocytes (PMN) from patients with type II diabetes, from elderly healthy, and from young healthy controls has been investigated by two techniques. Partial micropipette (i.d. 2.7–4.0 μm) aspiration of individual PMNs under constant aspiration pressure of 8 mm H2 0 and measurement of the aspirated length as a function of time (creep experiments) and filtration studies, using the Hemorheometer, of PMN suspensions (2.2·106 cells/ml) through 5 μm Nuclepore filters under 6 cm H2 0 driving pressure have been carried out. The creep curves were similar in all three cases with both the diabetic and…the elderly PMN showing a statistically significant decrease (p<0.001) from the control ones in deformability, while there was no significant difference between them. The initial filtration flow rate experiments (performed only on diabetic and control samples) exhibited a decreased deformability of the diabetics, which was not statistically different, however. The increased rigidity of these leukocytes in diabetes and in ageing may be a contributing factor in the observed microvascular flow disturbances in these situations.
Abstract: A system for direct observation and video recording of red blood cells (RBC) under flow, and computerized analysis of their aggregability was constructed. A narrow-gap flow-chamber was designed, in which a blood sample is subjected to controllable flow. Software was developed to provide the RBC aggregate size distribution at different shear stresses. From the size distribution curves the average or median size (or any other percentile) of the aggregate population as a function of shear stress, as well as the shear stress required for complete disaggregation, can be derived. The kinetics of spontaneous aggregation, in stasis, from singly dispersed cells,…as well as the disaggregation kinetics at varying shear stress, can be derived from temporal monitoring of the cells images. This system provides quantitative measures of RBC aggregability from direct visual monitoring of the aggregation and disaggregation processes.
Abstract: The change of rheological properties of blood during aggregation and subsequent sedimentation of erythrocytes was monitored by a new rheological technique. A damped oscillation type rheometer used can sensitively measure logarithmic damping factor (LDF) which is closely related to fluidity or/and viscosity and viscoelasticity of blood. The LDF value increased and then decreased with the progress of aggregation and sedimentation of erythrocytes. The results were compared with the Westergren method which has been still used as a routine examination of erythrocyte sedimentation (ES) in clinical practice. Good correlations between the LDF curve and the ES curve were observed in blood…of normal subjects and patients with different diseases. It is shown that the present method is capable of estimating the value of erythrocyte sedimentation at one hour within 10 to 20 minutes.
Keywords: erythrocyte sedimentation rate, aggregation of erythrocytes, rheological measurement, damped oscillation rheometer, the Westergren method
Abstract: The flow properties of aggregating red cell suspensions flowing at low rates through horizontal tubes are analyzed using a theoretical model based on microscopic observations. It is assumed that aggregated red cells form a cylindrical core which is eccentrically located in a horizontal tube due to sedimentation in a steady-state. The cylindrical core surrounded by a uniformly dispersed suspension of individual red cells moves with a uniform velocity along the tube axes. The velocity distribution within the tube is calculated on the assumption of unidirectional, incompressible flow. From this result the relative viscosity is obtained as functions of the size,…eccentricity and hematocrit of the core and a discharge hematocrit. It is shown that the relative viscosity increases monotonically with increasing the eccentricity. The simplified model also shows the presence of a certain condition under which the relative viscosity of aggregating red cell suspensions becomes lower than that of non-aggregating suspensions.
Keywords: red cell aggregation, rouleaux, blood viscosity, red cell sedimentation, microcirculation
Abstract: The two major determinants of rouleaux formation in a red cell suspension are the properties of the aggregant (its molecular form, concentration etc) and of the erythrocyte (its deformability, membrane properties, shape etc). While much is now known about the former, relatively little information is available on the latter, and particularly on the membrane factors that are important. One way of obtaining insight into this area is to degrade the membrane with various enzymes and observe their effects on rouleaux formation. This paper is intended as a short review of the field.
Abstract: We have measured deformability of leucocyte subpopulations by a filtration method in long-standing type 1 (insulin-dependent) diabetic patients and in type 2 (non-insulin dependent) diabetic patients compared with control subjects to determine if leucocyte deformability is impaired in diabetes, particularly in association with microvascular complications. Mononuclear leucocytes deformed less readily than polymorphonuclear leucocytes in both diabetic and non-diabetic subjects. There was no significant difference in either mononuclear or polymorphonuclear deformability between either group of diabetic patients and control subjects, but there was a significant association of age with both decreasing mononuclear and polymorphonuclear deformability. Diabetes does not adversely…affect leucocyte deformability and therefore altered leucocyte rheology is unlikely to be causally related to microvascular complications in longstanding diabetes. However increased leucocyte rigidity associated with advancing age could have detrimental effects on microvascular perfusion, which may be a determinant of organ damage in patients with macro and/or microvascular disease.
Abstract: The rheological action in human erythrocytes of oxpentifylline, a synthetic dimethyl xanthine, has been studied using blood from healthy controls and from patients with sickle cell anaemia. Calcium flux measurements using 45 Ca and the dihydropyridine D-600 (methoxyverapamil) were used to define a specific fraction of Ca entry into human erythrocytes. Oxpentifylline was found to inhibit the D-600-sensitive Ca flux (IC50 in the order of 0.5 mM) and may therefore protect sickle cells against Ca-mediated dehydration. Sickle cells were then dehydrated by 15 hours of cyclical oxygenation-deoxygenation in Ca-containing buffer. Oxpentifylline (1 μM–5 mM) failed to prevent Ca-induced loss…of cation via the K efflux (Gardos) channel. Thus the inhibitory effect of oxpentifylline on mediated Ca-entry is insufficient to prevent Ca-dependent dehydration of sickle cells. Inhibition of the Gardos channel in addition would seem to be necessary for a significant anti-sickling effect.
Abstract: To elucidate the pathophysiologic significance of the mechanical fragility of red blood cells (RBC), we have developed a simple quantitative technique, the impact-force method, for measuring mechanical hemolysis; the method makes use of the instantaneous falling of a metal bar due to gravity. The mechanical hemolysis thus induced was accompanied by cell fragmentation and echinocytosis. The method can be performed under near physiologic conditions. We found that mechanical hemolysis increased with a rise in hematocrit (Hct) value; in particular, the hemolysis rapidly increased above a Hct value of around 50%, thereby suggesting that the mechanical fragility determined by this method…reflects the rheologic characteristics of the RBC suspension, such as cell-cell interactions, as well as membrane stability. Using the impact-force method, we found that the mechanical fragility of rat RBC was greater than that of human RBC, whereas there was little difference between the two species in osmotic fragility. Although osmotic hemolysis was strongly reduced by low concentrations of chlorpromazine, this drug promoted mechanical hemolysis at all concentrations examined. More interestingly, Heinz body-forming RBC from a patient with unstable hemoglobin disease and hemolytic anemia showed a marked increase in mechanical fragility, but a pronounced decrease in osmotic fragility due to dehydration of the cells. This suggests the pathophysiologic importance of the mechanical fragility of RBC, specifically in the pathogenesis of hemolytic disease. It is, therefore, likely that this mechanical fragility test could be of value in various related fields of clinical medicine, as well as hematology.
Abstract: To elucidate the pathogenesis of hemolysis in hereditary spherocytosis (HS), we studied the heterogeneity and deformability of red blood cells (RBCs), before and after splenectomy, in a typical patient with HS. RBC deform ability was measured with our recently developed nickel mesh filter with both 3μm and 5μm pores. HS RBCs showed a marked increase in osmotic fragility with a “tailed” osmotic-fragility curve; consistently, the density distribution of HS RBCs was markedly shifted to heavier cells, with a biphasic profile. HS RBCs, the dense cells in particular, showed a marked impairment in filterability through the 3-μm pore nickel mesh compared…with that through the 5-μm pores. It is, therefore, likely that the impaired deformability of HS RBCs arises from the decrease in the cell surface area to volume ratio and the high mean corpuscular hemoglobin concentration. After splenectomy, the dense microspherocytes disappeared, and there was a marked improvement in RBC filterability through 3-μm pores. This suggests that dense cells were microspherocytes that received splenic conditioning in the walls of splenic sinuses. Correspondingly, splenectomy markedly improved clinical manifestations and ameliorated hemolysis. Thus, the laboratory measurement (i.e., the 3-μm filtration test) reflected the patient's clinical state. The use of both 5- and 3-μm filtration measurements can make a practical contribution to determining the differential diagnosis of hereditary hemolytic anemias. The 3-μm filter is useful in determing the clinical severity and indications for splenectomy in HS.
Abstract: The intrinsic resistance of red blood cell (RBC) is a determining factor of the blood viscosity. Hematocrit (Ht) greater than 60% significantly contributes to an increase in this factor. This study determines the viscosity of the intracellular content of RBC in neonates with and without polycythemia. The viscosity is measured in two neonate groups, according to the absence of illness and their hematocrit values, using capillary tubes with a 0.38 mm diameter at 25° C. The internal viscosity was found to be lower in polycythemic neonates together with lower plasma viscosity and mean corpuscular hemoglobin levels. The relative viscosity was…significantly greater in the polycythemic group. We draw the conclusion, that viscosity changes due to increased hematocrit are compensated by decreases in the plasma and internal viscosities of the red blood cells thus minimizing their effects on tissue blood flow.
Abstract: Activated leukocytes are known to generate reactive oxygen species which may attack other cells in their surroundings. On the other hand, rheological properties of red blood cells (RBC) are affected by oxidant attack. This study was designed to determine the influence of activated leukocytes on RBC rheology in vitro. Activated leukocytes were isolated from the Guinea pigs with an induced E. Coli sepsis and incubated with RBC obtained from normal animals. After two hours of incubation with activated leukocytes, RBC deform ability indices were increased 1.23 ± 0.05 (Mean ± Standart error) times (compared to the control RBC suspensions) while…incubation with leukocytes obtained from healthy animals increased deformability indices 1.12 ± 0.03 times. Thiobarbituric acid reactive substances as a measure of lipid peroxidation were increased 2.95 ± 0.36 times in the RBC suspensions incubated with activated leucocytes, but 1.70 ± 0.10 times in suspensions incubated with normal leukocytes. These results suggest that RBC mechanical properties might be affected by activated leukocytes and possibly an oxidative mechanism plays role in this interaction.
Keywords: Red blood cell deformability, oxidant attack, leukocytes, lipid peroxidation
Abstract: The capacity of red blood cells to deform is of crucial importance for both macro and microcirculation. A satisfying technique for the measurement of this parameter is lacking so far. We have developed and tested in various studies an instrument for automatic measurement of red cell deformability by laser diffractometry. Recently, it appeared that the applicability of the instrument could be extended for measuring another structural hemorheological parameter, red blood cell aggregation. In this communication, a description of the Laser-assisted Optical Rotational Cell Analyser (LORCA) is followed by the general methodology for the measurement of both red blood cell deformability…and aggregation, demonstrating the practical versatility of this instrument in the field of hemorheology.
Abstract: Red blood cell deformability was measured under normal and experimental conditions with the Laser-assisted Optical Rotational Cell Analyser (LORCA). Results were compared to simultaneously performed filtration measurements using the Cell Transit Analyser (CTA). The deformability parameters of the two methods were Elongation Index (EI) and mean Cell Transit Time (CTT), respectively. Aside from instrumental and intra-individual reproducibility, normal values, the effect of sample aging and of changing medium osmolality are reported. Furthermore, the respective sensitivities were determined using red blood cells with slightly impaired deformability. Both heat treatment and incubation in the presence of low concentrations of glutaraldehyde are…used to manipulate the deformability of the entire red cell population. It is concluded that minor defects in red blood cell deformability are detected more easily by the laser technique than by filtration. Even when the absolute differences in EI are small, they can be significant due to the very high reproducibility of the ektacytometric technique. Differentiation between a decreased deformability of the entire RBC population and the presence of a small (i.e., 5% or higher) subpopulation of rigid cells can be achieved with the LORCA by combining the measured EI-values with visual inspection of the diffraction pattern. Finally, no significant correlation was found between the results of both techniques applied to blood from 525 patients with various diseases.