Clinical Hemorheology and Microcirculation - Volume 12, issue 2
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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.
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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: The transformation of sickle hemoglobin molecules into arrays of fibers is the primary event in the pathophysiology of sickle cell disease. The process involves two types of nucleation: homogeneous nucleation in bulk solution, and heterogeneous nucleation onto other polymers. The polymers grow from each homogeneous nucleus in domains which ultimately become radial. Monomer diffusion into a domain can create density gradients between domains. Both types of nucleation are exquisitely concentration sensitive and can occur in times as short as milliseconds, while alignment and diffusion are less sensitive and take seconds or more. These various processes and their kinetics are reviewed…in light of their role in the pathophysiology.
Abstract: Cell dehydration due to loss of KCl is an important determinant in the pathogeneSiS of sickle cell anemia. The polymerization of hemoglobin S and cell sickling are markedly affected by an increase in the intracellular concentration of hemoglobin. Dense, dehydrated cells have been implicated in the vascular and vasoocclusive manifestations of this disease. Two systems for K transport, the KCl cotransport and the Ca-activated K channel, can lead to dehydration of sickle cells. Cellular acidification leads to activation of the KCl cotransport whereas transient increases in free cytoplasmic Ca lead to opening of the Ca-activated K channel. Maturation of normal…reticulocytes takes place through a loss of membrane area and of cell K, Cl and water. The KCl cotransport system is a major determinant of the K loss and cell dehydration of normal maturing reticulocytes. Therefore, common mechanisms leading to K loss and dehydration are operative in normal red cells and in sickle erythrocytes.
Keywords: Sickle cell, anemia, K transport, erythrocyte
Abstract: Erythrocytes (RBC) from patients with sickle cell anemia are abnormally adherent to vascular endothelium, and this is believed to participate in development of microvascular occlusion. Various studies of this phenomenon have disagreed regarding mechanism of adhesivity and identity of the most adherent RBC subpopulation. The data can be reconciled by recognizing that several factors may influence adhesivity and lead to variable participation by multiple mechanisms.
Keywords: sickle, erythrocyte, endothelium, vasocclusion, reticulocyte, plasma protein
Abstract: Microcirculatory flow behavior of sickle (SS) blood is significantly influenced by a variety of cellular and vascular factors. In the oxy state, hemodynamic abnormalities of SS red cells are caused by an elevated mean corpuscular hemoglobin concentration (MCHC) and the presence of irreversibly sickled cells (ISC). Further, microvascular flow behavior of SS red cells is highly sensitive to the level of oxygen tension and the amount of intracellular hemoglobin S (HbS) polymer; the latter is dependent on the MCHC differences in heterogenous SS red cells. The HbS polymer characteristics of SS red cells, as determined by the rate and duration…of deoxygenation, may also play an important role. The microvascular factors that are known to influence the flow behavior of SS red cells are the vascular topographical features, perfusion pressure, arteriovenous wall shear rate gradients, endothelial-derived substances (e.g., von WiIlebrand factor), and the vascular tone. In the ex vivo mesocecum microvasculature, infusion of SS red cells is followed by adhesion of these cells exclusively to the venular endothelium. The observed inverse correlation of SS cell adhesion with the venular diameter is in accordance with the arteriovenous wall shear rate profiles in the microcirculation. Thus, the narrow immediate postcapillary venules show the highest incidence of adhesion. In addition, random trapping of ISC may occur at arteriolar-capillary junctions. Microvascular obstruction can be caused by a combination of precapillary obstruction by ISC, adhesion in postcapillary venules, and secondary trapping of dense SS red cells (high MCHC), which may induce local hypoxia, increased polymerization of HbS, and rigidity of SS red cells. In the steady state, appropriate adjustments in the vascular tone may help dislodge such ensuing obstructive events.
Keywords: Microcirculation, Sickle Erythrocytes, hemodynamic, adhesion, von Willebrand factor, vasoocclusion
Abstract: Sickle-cell anaemia is the classical example of a rheological disorder, the poorly deformable sickle cell being responsible for impaired blood flow in the microcirculation causing intermittent tissue ischaemia. Loss of cation and water is a striking feature of the sickle cell, the consequential increase in concentration and polymerization of sickle haemoglobin causing an increase in cytoplasmic viscosity as quantified by impaired cell filterability through pores of 5μm diameter. Filtration methodology has been of particular value for studying the pathogenesis of cellular dehydration, for monitoring rheological changes during vaso-occlusive crisis, and for studying the action of drugs that inhibit cation flux…across the cell membrane and thus preserve cell water. Such membrane active drugs include Ca2+ -channel blockers (nitrendipine and nifedipine), Gardos channel inhibitors (cetiedil citrate, bepridil and nitrendipine), KCl cotransporter inhibitors, and drugs with a less specific or uncertain action (ticlopidine, oxpentifylline and piracetam). Serial ex vivo rheological studies during clinical trials of anti-sickling drugs offer an attractive method of monitoring efficacy. Such rheological measurements can be used instead of clinical end-points in pilot studies or to complement clinical end-points in multi-centre therapeutic trials. The application of rheological methods has substantially improved understanding of the pathogenes is of sickling and now provides a scientific basis for the evaluation of anti-sickling drugs.
Abstract: Blood and plasma viscosity were measured in 10 patients, before and after administration of the nonionic contrast medium Iopromide for coronary angiography. In all patients the hematocrit dropped markedly; the mean (± SD) value decreased from 0.425 ± 0.036 to 0.386 ± 0.037 (p < 0.001). The mean blood viscosity also decreased significantly, in a dose-dependent way; this effect could be entirely explained by the change in hematocrit. Plasma viscosity remained constant despite the high viscosity of the contrast medium. The drop in hematocrit was caused by the volume of the contrast medium plus a shift of water from extravascular…spaces to plasma, due to the high osmolarity of the contrast agent. The contrast medium studied is unlikely to cause clinically relevant late effects on blood rheology other than hemodilution.
Abstract: Addition of low doses of Hydergine® , a drug containing a mixture of hydrated ergotalkaloids to hyperosmolar blood in vitro leads to a dose-dependent increase in erythrocyte filterability through a 8 μ filter system. The concentrat ions of Hydergine® used in the present experiments ranged from 0.04675–6.0 mg Hydergine/l00 ml blood. Blood samples were incubated for 90 min at 37° C, measuring temperature was also 37° C. It could be shown that the drug-induced increase in erythrocyte filterability was not dependend on the presence of leucocytes. At higher osmolarity values, when the erythrocytes were more rigid, higher concentrations of…HydergineR were needed in order to obtain a comparable improvement in red cell filterability.
Abstract: Free radicals produced during cardiopulmonary bypass (CPB) stimulate lipid peroxidation reactions in the living cells. The blood cells are particularly vulnerable due to trauma of CPB which reduce their rheological function, thereby affecting the microcirculation in the body. The effects of Alprostadil (Synthetic Prostaglandin E1: S-PGE1) during CPB on lipid peroxidation caused by oxygen free radical (OFR) production and blood cell rheology were studied. The plasma malondialdehyde (MDA) was used as a marker for lipid peroxidation reactions. Red cell flltration rate (RFR) and white cell filtration rate (WFR) were measured as indices of blood cell rheology. Twenty four patients were…studied, 12 received PGE1 infusion (20 ng/kg/min) intraoperatively and 12 served as controls. RFR, WFR and MDA were measured before the start of CPB, after release of the aortic cross clamp and at the end of CPB. The production of MDA was significantly lower in the PGE1 group when compared to the controls (P<0.00l). Concomitantly, RFR and WFR in the PGE1 group were kept near to the prebypass values while both values reduced markedly in the control group (P<0.00l). These results indicated that the beneficial effect of PGE1 on RFR and WFR may be related to an inhibitory action of PGE1 on the release of free radicals during CPB as well as having a cellular protective action against OFR injury. The preservation of blood rheology and the limitation of OFR generation during CPB is advantageous to the vital organs.
Keywords: Free Radicals, Defonnability, Microcirculation, Organ Dysfunction, Cardiopulmonary Bypass
Abstract: Plasma viscosity, erythrocyte aggregation and platelet aggregation were determined in 4 patients suffering from pseudotumor cerebri. The results revealed hemorheological abnormalities in all patients. Plasma viscosity was elevated in 4, erythrocyte aggregation in 3 and platelet aggregation in one case. An involvement of hyperviscosity in the pathophysiology of PC is discussed.
Abstract: In a pilot study, fifteen chronically hemodialysed patients with severe hypertriglyeridemia (>350 mg/dl) received polyunsaturated fatty acids corresponding to 1.26 g/day eicosapentaenoic acid and 0.9 g/day docosahexaenoic acid over a period of six months in addition to their normal diet. At the beginning and after 2, 4 and 6 months of fish oil administration, laboratory and hemorheological parameters were determined. Initially, all hemorheological and clinical chemical parameters relevant for lipid metabolism were increased. A decrease in plasma triglyceride, total cholesterol, LDL, VLDL and apoprotein A1 fractions together with an increase in HDL fraction were observed during the fish oil treatment.…These significant changes were in well accordance with changes in hemorheological parameters. At the end of the study both the viscous and elastic components of complex viscoelasticity, aggregation index, flexibility index, and viscoelastic phase angle were significantly decreased, whereas the plasma viscosity, hematocrit and fibrinogen contents remained unchanged. Total protein and α2 -macroglobulin contents were also significantly reduced. Parallel measurements showed that during treatment the concentration of the applied ω-3 fatty acids in the red cell membrane increases significantly and that of arachidonic acid decreases. Thus the improvement in flow properties may result from adherence of fatty acids to the phospholipids of the red cell membrane, which leads to a reduction in membrane rigidity and aggregation tendency. It can therefore be concluded that long term low dose fish oil supplementation in hemodialysis patients reduces the increased lipid levels and improves the flow properties of blood into the normal range. Thus two risk factors concerning thrombosis and cardiovascular diseases can be positively influenced.
Abstract: Filtration of blood cells through 3 μm and 5 μm Nuclepore membranes has been studied under air and nitrogen. Experimental hypoxia had no effect on the morphological appearance of leukocytes nor their filterability through the 5 μm pores. However the combination of hypoxia and attempted filtration through 3 μm pores caused extensive morphological changes in leukocytes that was characterized by significant pore blocking during filtration. Hence hypoxia alone does not stimulate morphological changes in leukocytes but the combination of hypoxia and slow deformation through narrow pores may well lead to activation of leukocytes in vivo with trapping of red cells…and extensive pore blocking.
Abstract: We investigated the effect of a new antiplatelet agent, MCI-9042 ((±)-2-(dimethylamino)-1-[[o-(m-methoxyphenethyl)phenoxy]methyl]ethyl hydrogen succinate) on the deformability of red blood cells (RBC deformability). In the ftltration tests with whole blood and washed red blood cell suspension through Nuclepore ftlter, MCI-9042 improved filterabilities. Furthermore, MCI-9042 inhibited shear stressinduced hemolysis in turbulent flow. These results in the three assessment systems on RBC deform ability indicate that MCI-9042 exhibits an improving effect on the deform ability of red blood cells and the efficacy of MCI-9042 is more potent than that of pentoxifylline. From the studies on the mode of action of MCI-9042 on RBC…deform ability, we found that this compound reduced the membrane microviscosity of red blood cells. It is therefore considered that MCI-9042 directly affects the membrane of red blood cells reducing their membrane microviscosity and consequently improves RBC deform ability.
Keywords: MCI-9042, Red blood cell, Deformability, Membrane microviscosity
Abstract: The present work reports the hemorheologic changes and its role in the acute lung injury. The blood viscosity, particularly at low shear rate, increased significantly in the early stage of the lung injury and blood viscosity at 100S−1 increased obviously only from 240 min after oleic acid infusion. The analysis of stepwise regression on O2CT and related parameters at different time suggested that the parameters which had the greatest effect on O2CT changes are blood viscosity at low shear rate, hematocrit and erythrocytes aggregation. Thus, we conclude that the hemorheologic changes play an important role in acute lung injury…and that it is inappropriate that the increase of pulmonary flow resistance was only attributed to the decrease of microvascular radius.
Abstract: An in vitro model was designed to examine the role of ischemialreperfusion and oxygen-derived free radicals on red blood cell (RBC) injury. Normal human RBC suspensions were subjected to various times of hypoxia (1 to 30 min.) followed by various times of reoxygenation (1 to 30 min.). Using a filtration technique, a decrease in RBC deformability was then observed with a maximal effect after 5 min. hypoxial 5 min. reoxygenation. Superoxide anions and hydrogen peroxide could be implicated in this phenomenon, since superoxide dismutase (30 to 300 U/ml) and/or catalase (30 to 300 U/ml) efficiently prevented the membrane rigidity.…This study underlines the role of free radicals on RBC functionality and emphasizes the potential use of free radical scavengers in post-ischemic disorders.
Abstract: To evaluate fetal erythrocyte functions in the hypoxic environment during delivery, we measured fetal erythrocyte deformability and examined its relationship to various factors affecting it in 102 fullterm, vaginally delivered fetuses. Erythrocyte deformability at delivery was higher in umbilical arterial blood than in umbilical venous blood, and much lower in maternal blood than that in umbilical vessel blood. Erythrocyte deformability was significantly greater in both an asphyxiated group (1-minute Apgar score ≤ 7) and an acidotic group (pH≤ 7.20) than in a normal group (1-minute Apgar score ≤ 8, pH> 7.20, respectively). The PO2 in umbilical arterial blood was…significantly lower than in umbilica1 venous blood. Umbilical blood erythrocyte ATP was significantly higher than that in maternal blood. Erythrocyte deformability in umbilical arterial blood was negatively correlated with umbilical arterial blood PO2 (r=−0.63, n=102, p< 0.001) but positively correlated with erythrocyte ATP level (r= 0.76, n=72, p< 0.001). Umbilical arterial blood erythrocyte ATP was negatively correlated with umbilical arterial blood P02 (r=−0.75, n=72, p< 0.001). These findings suggest that in the hypoxic environment during delivery, fetal erythrocyte deformability is enhanced by the reduced PO2 and the increased erythrocyte ATP levels.
Keywords: Erythrocyte, Deformability, Fetal hypoxia, Delivery, ATP
Abstract: Plasma viscosity is used as an alternative to the erythrocyte sedimentation rate (ESR) as a test of the acute-phase response. To determine the effect on these tests of delay between venepuncture and time of testing we have stored plasma and whole blood samples from 39 individuals for 7 days at both 4°C and room temperature (RT). Serial daily testing showed no significant change in the plasma viscosity of separated plasma stored at 4°C or RT or of whole blood stored at 4°C. Whole blood stored at room temperature was stable for 4 days. A closed-tube system was used to determine…the stability of the ESR at 4°C, but there was still a progressive fall in the ESR value over 7 days of storage. This study confirms the validity of plasma viscosity measurements when there is a delay in separation of plasma and/or testing.