Clinical Hemorheology and Microcirculation - Volume 4, issue 2-3
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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: The human red cell may be dangerous because of individual abnormalities or collectively because of a high concentration. The normal range of red cell concentration is probably not optimal and between 1% and 4% of the population are at a significantly increased risk of cardiovascular complications because of a high red cell concentration, albeit within the normal range. There is evidence that it may act as both a primary and a secondary risk factor. A number of mechanisms may mediate this pathological effect, including a direct effect on blood viscosity and bulk blood flow, an effect on platelet aggregation and…haemodynamic effects predisposing to thrombogenesis. The true optimal red cell concentration depends on larger number of variables than is usually accepted and may vary from individual to individual. The therapeutic value of normovolaemic haemodilution is discussed in this context.
Keywords: Red cell concentration, optimal haematocrit, cardiovascular risk factor, haemodilution
Abstract: The procedures of hypervolemic hemodilution (by infusion of colloidal solutions) and of isovolemic hemodilution (by exchange of colloidal solution against whole blood) have been shown to improve cerebral perfusion. In this review, the literature and the personal experience of the author in this field is evaluated. The concept of rheological improvement of cerebral perfusion was originally developped from the epidemiological observations which clearly identified high hemoglobin levels (or high hematocrit) as an important risk factor for cerebrovascular disease. These findings are in keeping with the extensive clinical experience that high hemoglobin concentration is associated with a reduction not only in…global cerebral perfusion, but also in cerebral red cell flux (flow multiplied by hematocrit). Conversely, anemia is associated with increased cerebral perfusion; there is no evidence that anemia is associated with neurological deficits. Various procedures to reduce hematocrit resulted in improved perfusion of cerebral and peripheral vascular beds in patients. These global results do not allow to draw firm conclusions about the mode of action: arguments for the action of whole blood and plasma viscosity, of the oxygen transport capacity or of vasodilator responses are reviewed. In closing, the clinical results of retrospective and of prospective studies of the principle of hemodilution, presently available, are summarized, as are adequate procedures for its application to patients.
Abstract: The effects of orally administered drugs on blood rheology and their clinical effects in peripheral and cerebral ischaemia are reviewed. Measurements of red cell deformability remains a major problem, and more sensitive and specific methodology is required for pharmacological studies. Stress tests of red cells are interesting models to investigate drug protection against cell rigidity, but which tests to choose is unclear. There is a lack of long-term, placebo-controlled, double-blind studies of the effects of conventional oral doses on blood rheology ex vivo in patients. Such studies might usefully be combined with future studies of clinical efficacy, which would…then allow correlation of rheological and clinical effects.
Abstract: Hemorheologic changes may be primary, associated, or secondary, in relation to arterial disease and ischaemic damage. Therefore the significance of the hemorheologic changes in the pathophysiology of POAD, also in view of a therapeutic approach, needs careful assessment in each patient. Goals of the “hemorheologic” treatments in POAD are: 1) to induce a moderate lowering of peripheral resistance even when the vasodilatory reserve has been exhausted; 2) to improve blood flow in the microcirculation; 3) possibly, to increase blood flow in the newly formed collateral vessels. Some therapeutic measures dramatically altering blood rheology have been reported as effective in critical…phases of POAD, thus proving that lowering of blood viscosity improves blood flow and clinical conditions in certain groups of patients. Recent trials with “hemorheologic” drugs, mostly acting on blood filterability, suggest that some of them may indeed be effective in improving the walking ability of patients with intermittent claudication. However, the relation between hemorheologic and therapeutic effects of these drugs is not yet established. It is suggested that these drugs may be especially effective in a number of “good responders”, whose identification is however still doubtful.
Abstract: Rheological methods have much to contribute to better understanding of the microvascular changes that characterise the asymptomatic steady state and the painful vaso-occlusive crisis of sickle-cell anaemia. Loss of deformability of the reversibly sickled cell, rather than an increase in the number of irreversibly sickled cells or in plasma viscosity, is probably the important rheological change at the onset of vaso-occlusive crisis and can be measured using positive-pressure or initial-flow-rate filtration methods. These bulk filtration methods can also be used for in vitro screening of new anti-sickling compounds and to provide an objective end point, during clinical trials of…these compounds, of the resolution of crisis.
Abstract: The flow property of blood is one of the two major determinants of flow resistance, but it has not gained as much attention as the vascular component in haemodynamic investigations on ischaemic heart disease. Recent observations in some patients with typical angina pectoris but normal coronary arteriogram shed new light on this problem, since it became evident that merely severe rheological abnormalities can cause impaired coronary perfusion, while improvement of blood fluidity by plasmapheresis or haemodilution clearly increases coronary blood flow and coronary reserve. This, however, means that in coronary artery or small vessel diseases with already reduced flow forces…and restricted coronary reserve, rheological factors would be more relevant than it was expected until now. The more the vasomotor reserve is recruited the more likely are microcirculatory disturbances with clinical signs caused by pathologically altered viscosity factors. It is therefore of clinical interest that in most patients with common coronary artery disease the haemorheological parameters differ from normal. This is also true for non inflammatory and inflammatory small vessel diseases, where the changes are even more pronounced. Although rheological abnormalities can be determined in ischaemic heart disease it is not possible to forecast effects on coronary microcirculation as long as we have no data on the myocardial microhaemodynamic.
Keywords: Ischaemic heart disease, small vessel disease, plasma viscosity, red cell filtrability, red cell aggregation
Abstract: The Slit-Capillary PhotoViscometer allows a study of kinetics and morphology of aggregation of red cells. Micro and macro photography are carried out either during flow, or more frequently during stasis at 15 sec and 30 sec intervals. Colour slides are analyzed by stereological methods. Hereby three morphological indices are introduced based on the standard stereological parameters of Zeiss Videomat 2. Results for a specific stasis time can be compared using either Students t-test or by comparison of slopes and elevations of linear regressions linking various parameters and stasis time. Blood samples examined included a selection obtained from different patients, as…also a series of reconstituted suspensions at standard haematocrit of 30% but differing concentrations of albumin, fibrinogen, paraproteins, etc. Statistically significant differences have been observed using these parameters, both in kinetics and in morphology of blood samples.
Keywords: slit-capillary, aggregation of red cells, kinetics of aggregation, morphology of aggregation, stereological parameters, indices of morphology
Abstract: In vitro measurements with a transparent rheophotometer were carried out to study the spontaneous aggregation of red cells of 208 blood samples obtained from 132 children with different infectious diseases. The mean evaluation of aggregate formation in stasis (MEA) as well as of the erythrocyte sedimentation rate (ESR) was correlated with the concentration of most of the acute phase proteins of the plasma. The aggregate formation of erythrocytes (MEA) was more sensitively influenced by an increased concentration of the most important acute phase proteins than the erythrocyte sedimentation rate (ESR). A distinct correlation of red cell aggregation and the fibrinogen…concentration was found. We suggest, that the measurement of red cell aggregation is an appropriate method to describe the increase in the concentrations of the most important acute phase proteins, especially fibrinogen, during infectious diseases.
Abstract: The laser light scattered by erythrocytes subjected to a well defined shear stress can be analysed with the Ektacytometer to obtain information regarding the changes in all shape due to fluid shear. We used this technique for measuring cell deformation in different clinical status: diabetes, liver disease, geriatric population, arterial hypertension, and other clinical vascular disease. The results were compared to other biological parametes as: rheological parameters with a Couette viscometer, erythrocyte filtrability; coagulation and fibrinolytic parameters, tested as an index of a potent endothelial lesion. No reduced cell deformability was noted in clinical status at 290 mOs. However, by…modifying the osmotic strength of the suspending medium we can demonstrate the influence of S/V ratio and the internal viscosity upon erythrocyte deformability.
Abstract: A comparatively simple method is described for examining the clinical importance of red cell deformability in large numbers of patients. Using glass micropipettes in a thermostatically controlled unit, individual cells may be studied either in their native plasma or in buffer at varying pH, temperature and gas tensions. An apparatus has been produced which can make micro pipettes under reasonably controlled conditions of shape, diameter and length, with acceptable levels of production time and quality.
Abstract: Single erythrocyte passage time, flow curve in the Filtrometer, and Nuclepore filtration rate have been examined under different experimental conditions, which are supposed to simulate pathophysiological situations of diminished microvascular perfusion. The following methods have been used: 1. Nuclepore filtration test; 2. Filtrometer MF 4 (employing Nuclepore filters); 3. Single Erythrocyte Rigidometer (SER). To change RBC “deformability”, the cell suspensions have been treated with: 1. lactic acid (e.c. 0.1%); 2. 4h ageing in buffer; 3. CaCl2 (5 mmol/l); 4. adrenalin (0.1 and 0.316 mmol/l); 5. PGI2 (100 and 1000 ng/ml), and 6. PGE2 (0.3 ng/ml). The mean…passage time in the SER has been found to be significantly extended by all stress models applied, except for a non-measurable flow of RBC (e.g. occlusion) by the much too severe first stress model. In contrast, Nuclepore filtration test showed no effect on RBC deformability incubated with catecholamines and prostaglandins.
Abstract: The OP-Rheometer was developed to measure blood viscosity at lower shear rate (0.2–40 sec−1 ) and viscoelasticity at 0.1–3.0Hz in the context of clinical medicine. The system consists of a mechanical unit, a control unit, a data processing unit and a printer. The dynamic or constant flow data are automatically printed out. One of the features of this rheometer was a pair of magnetic bearings which supported an outer cylinder (blood sample container) connected to the torsion wire assembly. In clinical application, viscoelasticity of blood in diabetics showed higher level than that of normal subjects.
Keywords: viscoelasticity, OP-Rheometer, diabetes, rigidity modulus, loss modulus
Abstract: Recently, Whittington and Harkness (1) showed how whole-blood viscosities, as measured in a concentric-cylinder apparatus, could, in principle, be inferred from capillary-tube measurements made at rates of shear up to 1,000 times those in the rotary machine. Two invariant parameters, “A” and “β ” were postulated. “A” is the relative whole-blood viscosity at unit rate of shear and 1% haematocrit; and “β ” is the shear-sensitivity exponent. The ability of these parameters to discriminate between normal, hyperproteinaemic and sickle-cell bloods will now be demonstrated. It will be suggested that A and β may also be more useful indicators of…haemorheo1ogica1 reaction to surgery and drug-therapy than the data arising from whole-blood viscometry as usually presented. Hitherto, this art has generally implied the measurement of viscosity at selected constant shear-rates, often with a “correction” to an arbitrary haematocrit value. The new approach is to presume that A and β are constant characteristics of the blood-sample, quite independent of the haematocrit at withdrawal, and of the stresses imposed upon the blood during measurement.
Abstract: The maleimide-analogue sulfhydryl spin label MAL-6 has been used to study the motional and structural behavior of erythrocyte membrane proteins. Erythrocyte ghosts from insulin-dependent diabetic patients with long-standing complications were mainly examined. The ratios of weakly- and strongly- immobilized -SH groups were valued from the ESR spectra. The results indicate a high degree of resistance of the erythrocyte membrane to rapid bending rather than an increased resistance to translational motion.
Abstract: Decreased blood filterability has been found in intermittent claudicants, compared to age matched controls. An analysis of the initial filtration rate and of filter plugging showed: 1. Decreased filterability was caused essentially by filter clogging, rather than by change of initial filtration rate. 2. The remaining white cells in the suspension play a significant role in the plugging of the filter, however they cannot be held responsible for all the plugging observed. 3. Filtration tests measuring more than 0.1–0.2 ml suspension of 0.05 haematocrit are more sensitive to filter plugging than to red cell passage time. 4.…The measurement of red cell deformability (defined as transit time through a 5 µm pore) requires more sensitive methods than any of those used so far in clinical studies. 5. The white cell count in the buffy coat depleted blood was related to the plasma viscosity but not to the white cell count in the original whole blood, suggesting significant differences in cell adherence which might be an important factor 1n blood filterability. Decreased filterability was caused essentially by filter clogging, rather than by change of initial filtration rate. The remaining white cells in the suspension play a significant role in the plugging of the filter, however they cannot be held responsible for all the plugging observed. Filtration tests measuring more than 0.1–0.2 ml suspension of 0.05 haematocrit are more sensitive to filter plugging than to red cell passage time. The measurement of red cell deformability (defined as transit time through a 5 µm pore) requires more sensitive methods than any of those used so far in clinical studies. The white cell count in the buffy coat depleted blood was related to the plasma viscosity but not to the white cell count in the original whole blood, suggesting significant differences in cell adherence which might be an important factor 1n blood filterability.
Keywords: red cell filterability, red cell deformability, filter plugging, cell adherence
Abstract: The haemorheological traits were studied in 129 alcoholic liver diseases, 19 alcoholic patients without liver damage, 20 liver diseases without alcoholism and 50 controls. The methods included: 1) blood filtration, allowing an assessment of red blood cell deformability, plasma and whole blood viscosities, scanning electron microscopy; 2) in alcoholic group: intraerythrocyte ATP level, RBC membrane lipids analysis (cholesterol (e) and phospholipids (PL) content), search for correlations between initial blood filtration and MCV, rheological risk factors, blood filtration obtained after a fortnight’s alcohol withdrawal. In alcoholics, blood filterability was significantly decreased compared with non alcoholic liver diseases and healthy subjects. Plasma…and whole blood viscosities were raised, whereas ATP level dropped; increased cholesterol content induced a rise in C/PL ratio. These disturbances were correlated with morphological abnormalities observed with scanning electron microscopy. They were not correlated either with the severity of the liver disease (whether cirrhotic or non cirrhotic or non existent) or with macrocytosis and risk factors. They improved when patients were weaned from alcohol. Therefore red cell deformability abnormalities in alcoholics, purpose of the discussion, seem to be significant markers of alcoholism.
Keywords: Blood filterability, Plasma and blood viscosities, RBC ATP, Membrane lipids, Scanning electron microscopy, Alcoholism and liver disease
Abstract: The behaviour of haemorheological factors was studied by instrumental investigations in a group of 50 elderly subjects hospitalized for confusional states probably not secondary to an underlying organ pathology. Clinically, 19 were suffering from overall malnutrition, 30 from dehydration and one from frostbite. Substitute therapy given during hospitalization resulted in complete recovery in all patients. Although all haemorheological parameters had improved at the time of dischange, erythrocyte filtrability values never reached those of the normal control subjects. It is suggested that further studies should be carried out to establish whether there is a recognizable haemorheological pattern of aging in healthy…subjects, as well as to determine the effect that various nutrients and a state of dehydration exert on the haemorheological parameters.
Abstract: A near-zero gravity environment offers the elimination of some of the problems of handling heterogeneous systems such as blood in which the components are of disparate density and sedimentation of cells and buoyant convection occurs. Some of the physicochemical characteristics of blood are described, the basic variables measured in hemorheological studies discussed and the main effects of gravity or its absence on colloidal dispersions reviewed in relation to the effects which might be expected on the properties of blood and its constituents.