Clinical Hemorheology and Microcirculation - Volume 64, 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: The lecture was presented during the Fåhraeus award ceremony for 2016 at the University of Lisbon. It summarizes the main results and some of the more important hemorheological contributions achieved in the Laboratory of Biodynamics and Biorheology of the Institute of Mechanics to BAS and in collaboration with other laboratories of the research group, involved in many studies explaining hemorheological disturbances in various clinical conditions. An original method for the study of microstructural changes in the biological fluids by measuring the electrical conductivity simultaneously with the the rheological properties of red blood cells (RBC) in the whole blood and red…blood cell suspensions in a viscometric flow was suggested. The influence of the disturbed hemorheological parameters on the common carotid artery and cerebral blood flow was studied. Analysis of blood flow in the common carotid artery bifurcation with stenosis was done. This lecture does not claim to be a comprehensive review, and many important studies were not cited. The author would like to acknowledge the valuable collaboration of all those cited in the reference list.
Keywords: Hemorheology, cerebrovascular disease, diabetes mellitus type 2, electrorheological method, blood conductivity, common carotid artery hemodynamics, common carotid artery bifurcation, stenosis, numerical analysis
Abstract: Nitric oxide (NO) produced by endothelial cells interacts with erythrocyte through band 3 protein, being scavenged by haemoglobin. A signal transduction mechanism involving protein Gi and protein band 3 stimulates erythrocyte NO efflux when acetylcholine (ACh) binds to erythrocyte membrane acetylcholinesterase. Binding of normal plasma fibrinogen (Fib) levels, to erythrocyte membrane CD47 decreases the NO efflux. When high Fib concentration and ACh were present the efflux of NO from erythrocytes was normalized. The increased NO efflux from erythrocytes in presence of high Fib concentration and band 3 phosphorylation is reinforced in the presence of 4N1K an agonist peptide of CD47.…When both Fib and 4N1K are present the NO efflux from erythrocytes is higher or not affected according lower or high levels of cAMP. Erythrocyte NO efflux in patients with systemic lupus erythematous and rheumatoid attrite was significantly negative associated with carotid intima-media thickness. In patients with amyotrophic lateral sclerosis erythrocyte NO content is preserved and an inverse association between respiratory function and NO efflux from the erythrocyte was verified. Sepsis patients before dead at 24 h showed higher efflux of NO from erythrocytes that worsening the blood sub lingual microcirculation observed by high unequal blood flow and high microvascular flow index. The in vivo animal models either of inflammation or of hypertension evidenced that the NO efflux from erythrocyte decrease as a compensatory mechanism. All studies conducted since 2000 where we demonstrated the existence NO inside the erythrocyte by fluorescence microscopy, and after their signaling pathway needs more development translational research for news therapeutics and further application in not invasive therapy to vascular inflammatory diseases.
Keywords: Nitric oxide, erythrocyte, fibrinogen, signal transduction, inflammation, vascular diseases
Abstract: Vascular homeostasis involves endothelial function, smooth muscle function, central hemodynamics, and their interactions with blood. In this complex balance, the role of hemorheological parameters still needs to be defined, particularly with regards to its clinical implications. While the importance of microcirculation is being increasingly appreciated, the mechanisms of hemorheology and their implications are still not. This will be the challenge of our Society for the next years.
Abstract: The word “Biorheology” was introduced in 1948 during the first international congress on Rheology but “hemorheology” was first employed in 1951 during a meeting of the American Institute of Physics. Basically this science is related to physics and mechanics. The first international conference devoted to hemorheology was organized by AL Copley in Reykjavik (Iceland) in July 1969 and an International Society on Hemorheology was created. But after Reykjavik this society was named “International Society of Biorheology”. The term “Clinical Hemorheology” was proposed in Nancy in 1979 which was named “First European Symposium on Clinical Hemorheology” and an European Coordinating Committee…on Clinical Hemorheology (ECCCH) was created. The European Society on Clinical Hemorheology and Microcirculation was in fact created in Frankfurt in 1990 initiated by Albrecht Ehrly. In Nancy it was also decided to create a European Award named “Fahraeus Medal”. After Nancy, the ECCCH and the European Society organized symposia in London, Baden Baden, Sienna, Frankfurt, Bordeaux, ... , Sofia ... and now Lisboa. Now it is necessary to give new directions for the development of Hemorheology and Clinical Hemorheology. Different ways can be considered: – Development of new theoretical models which take into account the heterogeneity of blood and blood vessel – Research on cell mechanobiology and mechanotransduction (leucocyte, endothelial and smooth muscle cells) – Study of cellular interactions (aggregation, adhesion, ...) and intracellular transport – Membrane rheology and concept of molecular fluidity – Dynamic blood coagulation in relation with molecular reactions – Development of metrology for clinical hemorheology Development of new theoretical models which take into account the heterogeneity of blood and blood vessel Research on cell mechanobiology and mechanotransduction (leucocyte, endothelial and smooth muscle cells) Study of cellular interactions (aggregation, adhesion, ...) and intracellular transport Membrane rheology and concept of molecular fluidity Dynamic blood coagulation in relation with molecular reactions Development of metrology for clinical hemorheology
Abstract: An obvious candidate for the seminal event in the history of haemorheology is Harvey’s presentation of the concept of the circulation of the blood. Prior to this, the ideas concerning the movement of blood were based, in Europe and Middle East, largely on the principles laid down by Galen, and these had been, in effect, dogma for nearly a millennium and a half. These principles were basically that blood is formed in the liver, thence it travels to the bodily organs and is consumed –hence there is one-way flow and no circulation of the blood at all. Harvey’s revolutionary idea…that blood circulates repeatedly around the cardiovascular system laid the foundation for haemorheology because once that idea was accepted then the fluidity of the blood immediately became potentially of crucial importance – and haemorheology was conceived. In this paper the ideas that preceded Harvey will be presented, i.e. those of Galen, Ibn al-Nafis, Vesalius, Fabricius and Colombo etc. Harvey’s awareness of this background, due mainly to time spent in Padua, triggered his many experimental investigations and discoveries. Ultimately, these led to his astonishing insights published in De Mortu Cordis in 1628 which changed the understanding of the cardio-vascular system forever.
Abstract: Clinicians are used to treat individual patients, and therefore may feel that clinical trials and systematic reviews do not give information for optimal treatment of the single patient. Evidence Based Medicine (EBM) is the integration of research evidence (from clinically relevant studies conducted using sound methodology) with clinical expertise (clinician’s cumulated experience) and patient values (personal preferences and unique concerns and expectations). The practical steps of EBM include: 1) assess the patient, 2) ask the clinical question, 3) acquire the evidence, 4) critically appraise the evidence, 5) apply the results to the patient and 6) self-evaluate one’s practice. Clinical studies in clinical hemorheology…include – among other – interventions in vascular medicine: coronary disease, stroke, peripheral vascular disease, venous insufficiency and thrombosis, etc. Of these, we will present some practical steps on how to apply therapy results of stroke studies to the individual patient (this addresses step number 5 in the previous definition of EBM practice). We will do this by discussing the differences between internal and external validity of clinical trials, and defining the importance of baseline risks to choose therapy using the data from the best and most useful studies available. In the end, clinicians will understand how to use evidence effectively.
Abstract: In this ESCHM 2016 conference talk report, we summarise two recently published original articles Franco et al. PLoS Biology 2015 and Franco et al. eLIFE 2016. The vascular network undergoes extensive vessel remodelling to become fully functional. Is it well established that blood flow is a main driver for vascular remodelling. It has also been proposed that vessel pruning is a central process within physiological vessel remodelling. However, despite its central function, the cellular and molecular mechanisms regulating vessel regression, and their interaction with blood flow patterns, remain largely unexplained. We investigated the cellular process governing developmental vascular remodelling in…mouse and zebrafish. We established that polarised reorganization of endothelial cells is at the core of vessel regression, representing vessel anastomosis in reverse. Moreover, we established for the first time an axial polarity map for all endothelial cells together with an in silico method for the computation of the haemodynamic forces in the murine retinal vasculature. Using network-level analysis and microfluidics, we showed that endothelial non-canonical Wnt signalling regulates endothelial sensitivity to shear forces. Loss of Wnt5a/11 renders endothelial cells more sensitive to shear, resulting in axial polarisation at lower shear stress levels. Collectively our data suggest that non-canonical Wnt signalling stabilizes forming vascular networks by reducing endothelial shear sensitivity, thus keeping vessels open under low flow conditions that prevail in the primitive plexus.
Abstract: During the past decades, our group have investigated the hemorheological parameters (HPs) of more than 1,000 patients with various forms of ischemic heart disease (IHD). Our data indicate that HPs are altered in patients with IHD and the extent of the alterations is in good correlation with the clinical severity of the disease. Our findings have also proven that HPs play a critical role in the pathogenesis of myocardial ischemia. The lack of regular exercise is an important cardiovascular risk factor. Regular physical activity – as part of the cardiovascular rehabilitation training program (CRP) – is recommended for the…treatment of IHD and the prevention of first or further cardiovascular events. To estimate the beneficial hemorheological effects of CRP, compared to patients after a coronary event or intervention and not participating in CRP, the data of four of our prospective studies (three non-CRP and one CRP-participating) were evaluated. Hematocrit (Hct), plasma and whole blood viscosity (WBV), Hct/WBV ratio significantly (p < 0.05) increased in the non-CRP groups during the 6–12 months follow-up, while in the CRP group they significantly decreased (p < 0.05). Red blood cell aggregation decreased in a much greater manner in the CRP group. Our results indicate that CRP has beneficial hemorheological effects and is able to reverse the deterioration of HPs after coronary events or intervention.
Abstract: The hematocrit (Hct) determines the oxygen carrying capacity of blood, but also increases blood viscosity and thus flow resistance. From this dual role the concept of an optimum Hct for tissue oxygenation has been derived. Viscometric studies using the ratio Hct/blood viscosity at high shear rate showed an optimum Hct of 50–60% for red blood cell (RBC) suspensions in plasma. For the perfusion of an artificial microvascular network with 5–70μ m channels the optimum Hct was 60–70% for high driving pressures. With lower shear rates or driving pressures the optimum Hct shifted towards lower values. In healthy, well trained athletes…an increase of the Hct to supra-normal levels can increase exercise performance. These data with healthy individuals suggest that the optimum Hct for oxygen transport may be higher than the physiological range (35–40% in women, 39–50% in men). This is in contrast to clinical observations. Large clinical studies have repeatedly shown that a correction of anemia in a variety of disorders such as chronic kidney disease, heart failure, coronary syndrome, oncology, acute gastrointestinal bleeding, critical care, or surgery have better clinical outcomes when restrictive transfusion strategies are applied. Actual guidelines, therefore, recommend a transfusion threshold of 7–8 g/dL hemoglobin (Hct 20–24%) in stable, hospitalized patients. The discrepancy between the optimum Hct in health and disease may be due to factors such as decreased perfusion pressures (low cardiac output, vascular stenoses, change in vascular tone), endothelial cell dysfunction, leukocyte adhesion and others.