Clinical Hemorheology and Microcirculation - Volume 53, issue 1-2

Authors: Jung, F. | Niimi, H. | Forconi, S. | Stoltz, J.F.

Article Type: Other

DOI: 10.3233/CH-2012-1570

Citation: Clinical Hemorheology and Microcirculation, vol. 53, no. 1-2, pp. 1-2, 2013

Authors: Forconi, Sandro | Gori, Tommaso

Article Type: Research Article

Abstract: A number of factors are involved in the regulation and maintenance of vascular homeostasis. The role of the vascular endothelium has been identified almost three decades ago, and a number of lines of evidence provide solid support to the role of this tissue in modulating not only vascular tone, but also phenomena such as platelet, red blood cell aggregation and deformability. In turn, hemorheological characteristics have been proven to impact on the endothelial release of mediators and therefore on vascular tone. Both biochemical and physical stimuli are sensed by the endothelium as stimuli for the release of oxygen free radicals …and nitric oxide. In particular, changes in blood viscosity have a direct effect on shear stress, which is believed to be the physiological stimulus for endothelial activation. These considerations have lead us to formulate an alternative hypothesis for the meaning of hyperviscosity in the setting of ischemic syndromes. While this hypothesis is supported by animal data, the evidence of cross-sectional human studies is controversial. This evidence is discussed in the present review. Show more

Keywords: Endothelial function, viscosity, hematocrit, platelets

DOI: 10.3233/CH-2012-1571

Citation: Clinical Hemorheology and Microcirculation, vol. 53, no. 1-2, pp. 3-10, 2013

Authors: Wautier, Jean-Luc | Wautier, Marie-Paule

Article Type: Research Article

Abstract: Red blood cell (RBC) adhesion to endothelium can be studied in static and flow conditions. Increased RBC adhesion was first described in sickle cell disease. Several molecules were shown to be involved in this phenomenon: VCAM-1, α4β1, Lu/BCAM, ICAM-4. In malaria, Plasmodium falciparum erythrocyte membrane protein1 binds to ICAM-1, PECAM-1 and facilitates the parasite dissemination. In diabetes mellitus augmented RBC adhesion is correlated to the severity of vascular complications. Glycated RBC band3 reacts with the endothelial Receptor for Advanced Glycation End products (RAGE). RAGE engagement induced endothelial cell dysfunction. In patients with Polycythemia Vera (PV), the most frequent myeloproliferative disorder, …constitutive phosphorylation of RBC Lu/BCAM is responsible for an increased adhesion to endothelial cell laminin. Retinal vein occlusion (RVO) is a common cause of permanent visual loss. Spontaneous growth of erythroid precursors was observed in more than 25% of patients. RBC adhesion was enhanced and correlated to phosphatidyl serine (PS) expression on RBC. Anti-PS receptor blocked RVO RBC adhesion indicating that the counterpart of RBC PS is PS endothelial cell receptor. Erythrocyte adhesion is mediated by different molecule abnormalities in different diseases but is associated to a higher risk of thrombosis and vascular complications. Show more

Keywords: Red blood cell, endothelial cell, adhesion molecules, sickle cell disease, diabetes, malaria, polycythemia vera, retinal vascular occlusion

DOI: 10.3233/CH-2012-1572

Citation: Clinical Hemorheology and Microcirculation, vol. 53, no. 1-2, pp. 11-21, 2013

Authors: Baskurt, Oguz K. | Meiselman, Herbert J.

Article Type: Research Article

Abstract: Red blood cell (RBC) aggregate to form two- and three-dimensional structures when suspended in aqueous solutions containing large plasma proteins or polymers; this aggregation is reversible and shear dependent (i.e., dispersed at high shear and reformed at low or stasis). The extent of aggregation is the main determinant of low shear blood viscosity, thus predicting an inverse relationship between aggregation and in vivo blood flow. However, the effects of aggregation on hemodynamic mechanisms (e.g., plasma skimming, Fåhraeus Effect, microvascular hematocrit) may promote rather than impede vascular blood flow. The impact of enhanced RBC aggregation on endothelial function and hemostatic mechanisms …adds further complexity, thereby requiring specific attention to the nature, extent and time course of aggregation when considering its overall influence on tissue perfusion. A detailed understanding of aggregation effects is important from a clinical point of view since it may be enhanced during a variety of pathophysiological processes, including infections, circulatory and metabolic disorders, hematological pathologies and several other disease states. Altered RBC aggregation may be an indicator of disease as well as a factor affecting the course of the clinical condition; the prognostic value of RBC aggregation indices has been demonstrated in various diseases. Currently, RBC aggregation is an easily and accurately measurable parameter, and therefore may be expected to have broader clinical usage in the future. Show more

Keywords: Inflammation, aggregability, hemorheology, tissue perfusion

DOI: 10.3233/CH-2012-1573

Citation: Clinical Hemorheology and Microcirculation, vol. 53, no. 1-2, pp. 23-37, 2013

Authors: Saldanha, Carlota

Article Type: Research Article

Abstract: A brief review of the fibrinogen molecule composition and structure is presented like as an introduction to the effects of this plasma protein on the red blood cell hemorheoplogical properties namely erythrocyte aggregation tendency and deformability ability. The protein membrane RBC target for fibrinogen is also highlight as well as the erythrocyte signal transduction pathway associated with nitric oxide mobilization resulting from its binding.

Keywords: Fibrinogen, nitric oxide, CD47, erythrocyte aggregation, erythrocte deformability

DOI: 10.3233/CH-2012-1574

Citation: Clinical Hemorheology and Microcirculation, vol. 53, no. 1-2, pp. 39-44, 2013

Authors: Muravyov, Alexei V. | Tikhomirova, Irina A.

Article Type: Research Article

Abstract: This study was designed to investigate the dependency of the red blood cell deformability upon activation of extra- and intracellular signaling pathways. Exposures of red blood cells (RBCs) to catecholamines and to insulin led to positive change in the RBC deformability. When forskolin, a stimulator of adenylyl cyclase (AC), was added to RBC suspension, the RBC deformability was increased. Somewhat more significant deformability rise appeared after RBC incubation with dB-AMP. The inhibitors of phosphodiesterase (PDE) activity increased red cell deformability. These results revealed a considerable role of the AC-cAMP signaling system in the regulation of red blood cell deformability. The …rise of the red blood cell Ca2+ influx, stimulated by mechanical loading or A23187 was accompanied by a marked lowering of RBC deformability. At the same time blocking of Ca2+ entry into RBC by verapamil or Ca2+ chelating by EGTA led to significant deformability rise. The comparison of the effect of the different protein kinases on the red blood cell deformability showed that it was altered more considerable under PKA activation by forskolin or dB-cAMP than by other protein kinases. There was a lesser but quite statistically significant effect of tyrosine protein kinase (TPK) on RBC microrheology. Whereas the microrheological effect of PKC was not so considerable. The problem of the short-term regulation of red blood cell microrheology is examined. The latter includes: the modes of activation of extra- and intracellular molecular signaling pathways, ligand - receptor interaction, second messengers, membrane protein phosphorylation. On the whole the total data clearly show that the red cell deformability changes are connected with activation of different extra - and intracellular signaling pathways. It seems reasonable to suppose that red blood cell deformability changes were mainly associated with activation of the AC-cAMP-PKA pathway, and with decrease of Ca2+ entry into cells. Show more

Keywords: Red blood cell deformability catecholamines, insulin, acetylcholine, adenylyl cyclase, phosphodiesterase, membrane receptors, Ca$^{2+}$, protein kinases

DOI: 10.3233/CH-2012-1575

Citation: Clinical Hemorheology and Microcirculation, vol. 53, no. 1-2, pp. 45-59, 2013

Authors: Baskurt, Oguz K. | Meiselman, Herbert J.

Article Type: Research Article

Abstract: Comparative data on blood composition and blood flow properties indicate different levels of interspecies variation for several parameters. Hematocrit and hemoglobin levels have relatively low variability among mammals, while mean cell volume and red blood cell (RBC) count are more variable. There is also a difference of variability between high and low shear rate blood viscosity in mammals, with low shear rate viscosity having a higher degree of interspecies variation. This observation parallels the diversity of RBC aggregation among mammalian species. Allometric relations for blood rheology parameters indicate highly significant correlations of low shear rate blood viscosity and RBC aggregation …with body weight, especially if species belonging to the order Artiodactyla are excluded. These allometric relations can be used to formulate various hypotheses about the evolutionary histories of circulatory functions, as well as hypotheses related to the role of RBC aggregation in the mammalian circulatory system. Such comparative studies and analytical reasoning based on comparative data may contribute to answering the “why” questions, and accordingly may improve our understanding of circulatory functions and hence may have possible clinical importance. During the last several decades, similar approaches to various medical concepts have yielded a new approach to medicine that is now known as Evolutionary Medicine. Show more

Keywords: Evolution, darwinian medicine, comparative physiology, blood rheology, hemodynamics

DOI: 10.3233/CH-2012-1576

Citation: Clinical Hemorheology and Microcirculation, vol. 53, no. 1-2, pp. 61-70, 2013

Authors: Reinhart, W.H.

Article Type: Research Article

Abstract: Platelets play a key role in primary hemostasis and in the pathogenesis of atherosclerosis and atherothrombotic events such as stroke and myocardial infarction. When a plaque ruptures, platelets adhere to the underlying collagen matrix, become activated and aggregate, which may lead to vascular occlusions. Hemorheological aspects are intimately involved in this process. The assessment of this platelet function in vitro is difficult and has not reached the stage of routine use. Inhibition of platelet aggregation is the corner stone of any treatment of vascular disease. It is achieved mainly by to mechanisms, inhibition of thromboxane formation by acetylsalicylic acid, and …with ADP receptor antagonists such as clopidogrel. Newer agents are being developed with the difficult mission to inhibit platelet aggregation more efficiently, and simultaneously reduce the risk of bleeding. Show more

Keywords: Aggregation, atherosclerosis, erythrocytes, inflammation, platelets

DOI: 10.3233/CH-2012-1577

Citation: Clinical Hemorheology and Microcirculation, vol. 53, no. 1-2, pp. 71-79, 2013

Authors: Papp, J. | Kenyeres, P. | Toth, K.

Article Type: Research Article

Abstract: Platelets play an important role both in normal hemostasis and in pathological thrombus formation. Several large-scale clinical studies have proved that the inhibition of platelet aggregation results in a significant decrease in mortality and morbidity of ischemic atherothrombotic events, thus antiplatelet therapy became a key pharmacological method in prevention and treatment of such cardiovascular, cerebrovascular and peripheral arterial diseases. The present paper aims to give a brief overview of the most important antiplatelet drugs, their mechanism of action and their recommended usage in cardiovascular diseases. We also discuss possible methods to monitor the effectiveness of therapy and possible causes of …therapeutic failure. Show more

Keywords: Antiplatelet drugs, inhibition of platelet aggregation, coronary heart disease, stroke, peripheral arterial disease, aspirin and clopidogrel resistance, platelet aggregometry

DOI: 10.3233/CH-2012-1578

Citation: Clinical Hemorheology and Microcirculation, vol. 53, no. 1-2, pp. 81-96, 2013

Authors: Jung, F. | Braune, S. | Lendlein, A.

Article Type: Research Article

Abstract: Cardiovascular implants are increasingly important in regenerative medicine. To improve the safety and function of blood-contacting implants a major need exists for new polymer-based biomaterials that avoid adverse reactions, particularly thrombotic events. This review is aimed to summarize the multi-stepped and interlinked processes leading to a thrombus growth on body foreign surfaces: protein adsorption, platelet adhesion accompanied by activation and spreading and the release of substances of various organelles activating other neighboured platelets (and the plasmatic coagulation) leading to the formation of a plug of platelets and, finally, to a thrombus.

Keywords: Protein adsorption, platelet activation, platelet aggregation, foreign body

DOI: 10.3233/CH-2012-1579

Citation: Clinical Hemorheology and Microcirculation, vol. 53, no. 1-2, pp. 97-115, 2013

Authors: Menu, P. | Stoltz, J.F. | Kerdjoudj, H.

Article Type: Research Article

Keywords: Vascular substitute, endothelialisation, tissue engineering

DOI: 10.3233/CH-2012-1580

Citation: Clinical Hemorheology and Microcirculation, vol. 53, no. 1-2, pp. 117-129, 2013

Authors: Vayá, Amparo | Suescun, Marta

Article Type: Research Article

Abstract: The role played by hemorheological alterations in the development of deep vein thrombosis (DVT) has often been overlooked. Although marked rheological alterations and the relationship with thromboembolic events are well-defined in patients with hematological diseases such as myelom, Waldenström disease and polycythemia vera, the relationship is not so clear in patients without hematological diseases. In the present review, we analyzed studies evaluating the rheological profile in DVT patients. Among the cardiovascular risk factors, only hyperlipidemia, metabolic syndrome, tobacco and obesity increase DVT risk and, in addition, a disturbed rheological profile is shown which could further increase this risk. The significance …of hematocrit and fibrinogen, the main factors influencing blood viscosity, is not sufficient to increase blood viscosity in any of the studies analyzed. DVT patients show increased fibrinogen levels and erythrocyte aggregation throughout all the studies despite patients not being in an acute reactant phase. In addition to rheological alterations, it is necessary to consider local conditions at pockets of venous valves which undergo deterioration with aging and play an important role equally to alterations in the rheological profile. Moreover, it is necessary to take into account that systemic rheological alterations are not comparable to those in low shear rate areas where minimum disturbances could be more relevant. It would be convenient to perform multicentric studies with the same rheological methodology and pre-analytical procedures to evaluate, in order to obviate the effect of thrombophilic and circumstantial risk factors, rheological parameters in patients with spontaneous DVT to elucidate their real contribution to the development of thromboembolic events. Show more

Keywords: Deep vein thrombosis, hemorheology, cardiovascular risk factors

DOI: 10.3233/CH-2012-1581

Citation: Clinical Hemorheology and Microcirculation, vol. 53, no. 1-2, pp. 131-141, 2013

Authors: Franke, R.P. | Jung, F.

Article Type: Research Article

Abstract: Contrast media-induced nephropathy (CIN) is a known complication of intra-arterial application of radiographic contrast media (RCM) and is associated with both short- and long-term outcomes. The development of CIN is not easy to diagnose due to a lack of a uniform definition of CIN. CIN was reported in 4 to 20% of patients after intra-arterial RCM administration during coronary angiography. An all-cause mortality rate of CIN patients amounted to 9% compared with 2% among patients not developing CIN. Pre-existing chronic renal insufficiency, especially, was described as important factor predisposing for CIN, but there was recent clinical evidence that CIN may …occur also in low risk ambulatory patients, probably depending on the type of RCM used. Strongly depending on the type of RCM administered there were marked differences in the morphological changes of erythrocytes as well as endothelial cells coinciding in some cases with microcirculatory disorders in patients as well as in animal models. Iodixanol brought about the least cellular and microcirculatory effects while Iopromide induced the strongest disturbances in capillary perfusion and myocardial oxygen tension. It is unclear, however, whether this favours the development of CIN. Show more

Keywords: Iodixanol, Iopromide, microcirculation, blood cells, nephropathy

DOI: 10.3233/CH-2012-1582

Citation: Clinical Hemorheology and Microcirculation, vol. 53, no. 1-2, pp. 143-153, 2013

Authors: Al-Banna, N.A. | Pavlovic, D. | Gründling, M. | Zhou, J. | Kelly, M. | Whynot, S. | Hung, O. | Johnston, B. | Issekutz, T.B. | Kern, H. | Cerny, V. | Lehmann, Ch.

Article Type: Research Article

Abstract: The main function of antibiotics is related to their capacity to eliminate a microorganism. In addition to the antimicrobial function of antibiotics, they are known to have anti-inflammatory and vasomodulatory effects on the microcirculation. The ability of non-antimicrobial derivatives of antibiotics to control inflammation illustrates the distinct anti-microbial and anti-inflammatory roles of antibiotics. In this review, we discuss the impact of antibiotics on leukocyte recruitment and the state of the microcirculation. Literature reporting the effect of antibiotics in non-infectious inflammatory conditions is reviewed as well as the studies demonstrating the anti-inflammatory effects of antibiotics in animal models of infection. In …addition, the effect of the antibiotics on the immune system is summarized in this review, in order to postulate some mechanisms of action for the proand anti-inflammatory contribution of antibiotics. Literature reported the effect of antibiotics on the production of cytokines, chemotaxis and recruitment of leukocytes, production of reactive oxygen species, process of phagocytosis and autophagy, and apoptosis of leukocytes. Yet, all antibiotics may not necessarily exert an anti-inflammatory effect on the microcirculation. Thus, we suggest a model for spectrum of anti-inflammatory and vasomodulatory effects of antibiotics in the microcirculation of animals in local and systemic inflammation. Although the literature suggests the ability of antibiotics to modulate leukocyte recruitment and microperfusion, the process and the mechanism of action are not fully characterized. Studying this process will expand the knowledge base that is required for the selection of antibiotic treatment based on its anti-inflammatory functions, which might be particularly important for critically ill patients. Show more

Keywords: Antibiotics, microcirculation, leukocyte recruitment, inflammation, immune system

DOI: 10.3233/CH-2012-1583

Citation: Clinical Hemorheology and Microcirculation, vol. 53, no. 1-2, pp. 155-169, 2013

Authors: Clevert, D.A. | D'Anastasi, M. | Jung, E.M.

Article Type: Research Article

Abstract: Ultrasound is often the first imaging modality used in the diagnosis of abdominal vascular as well as parenchymal organ pathologies. Contrast-enhanced ultrasound (CEUS) enables the dynamic assessment and quantification of microvascularisation up to capillary perfusion. Current clinical applications of CEUS are mainly in detection and characterization of lesions, particularly benign and malignant hepatic and renal lesions, based on differences between lesion and organ perfusion. Multifrequency high-resolution transducers are being increasingly used, including intra-operatively. Dynamic 3D techniques and ultrasound image fusion with CT or MRI may assist the diagnosis and therapy control after interventional procedures. Our own studies have demonstrated the …excellent diagnostic performance of CEUS with perfusion-analysis in the characterization of hepatic and renal lesions as well as the assessment of tissue transplant macro- and microvascularisation. CEUS opens up new possibilities in the characterization of the microvasculature with perfusion analysis, even during the course of interventions, thereby providing new possibilities for modified therapeutic strategies. In this review, the different new ultrasound techniques with their potential applications are described and illustrated. Show more

Keywords: Contrast-enhanced ultrasound (CEUS), microvascularisation, perfusion analysis, image fusion

DOI: 10.3233/CH-2012-1584

Citation: Clinical Hemorheology and Microcirculation, vol. 53, no. 1-2, pp. 171-186, 2013

Authors: Connes, Philippe | Simmonds, Michael J. | Brun, Jean-Frederic | Baskurt, Oguz K.

Article Type: Research Article

Abstract: The present review focuses on the past and recent knowledge in the field of exercise hemorheology and presents some unresolved issues for opening discussion. Acute exercise is associated with a rise in hematocrit which results in an increase in blood viscosity. Whereas increased blood viscosity was previously viewed as having negative consequences for cardiovascular function and aerobic performance, recent findings suggest dynamic changes in blood viscosity might be useful for vascular function during exercise by increasing nitric oxide production. Other determinants of blood viscosity are altered by exercise (e.g., decreased red blood cell deformability, increased red blood cell aggregation and …plasma viscosity) and may, independent of the associated effect on blood viscosity, directly modulate aerobic capacity. However, the data published on the effects of exercise on the hemorheology are not consistent, with some studies showing decreased, unchanged, or increased red blood cell deformability/aggregation when compared with rest. These discrepancies seem to be related to the exercise protocol investigated, the population tested or the methodogy utilized for hemorheological measurements. Finally, this review focuses on the effects of training exercise training (i.e. chronic physical activity) on the hemorheological profile of healthy individuals and patients with cardiovascular and metabolic disorders. Show more

Keywords: Exercise, training, blood viscosity, plasma viscosity, red blood cell deformability, red blood cell aggregation

DOI: 10.3233/CH-2012-1643

Citation: Clinical Hemorheology and Microcirculation, vol. 53, no. 1-2, pp. 187-199, 2013

Authors: Jung, F. | Mrowietz, C. | Gerk, U. | Franke, R.P.

Article Type: Research Article

Abstract: Radiographic contrast media (RCM) are widely used to visualize blood vessels. Their effects on blood vessels should be minimal so that the object of the measurement – the vessel lumen - is not influenced by the RCM molecules. However, all RCMs exhibit a more or less strong effect on endothelial cells as well as on erythrocytes. These effects are discussed to induce a significant and relevant deceleration of the microcirculation. For some RCMs this could be demonstrated in animal or clinical studies. Therefore, this study investigated the role of the viscosity of a RCM on the mean erythrocyte velocity in …nail fold capillaries in patients with coronary artery disease after a bolus injection of the RCM directly into the A. axillaris. Iopentol-350 is a high-viscous Xray contrast medium and induced a short-lasting imbalance of the microcirculation already in vascular regions not affected by atherosclerosis. This effect was – in the early phase after injection – significantly stronger than after application of the low viscous Iopentol-150. In patients with severe coronary artery disease and a myocardial perfusion at its limits, the injection of high-viscous X-ray contrast media could induce massive perturbations in the microcirculation and even ischemia. As a consequence a further impairment of both systolic and diastolic functions may occur. Show more

Keywords: Radiographic contrast media, Iopentol, capillary perfusion

DOI: 10.3233/CH-2012-1557

Citation: Clinical Hemorheology and Microcirculation, vol. 53, no. 1-2, pp. 201-208, 2013

Authors: Silva-Herdade, A.S. | Saldanha, C.

Article Type: Research Article

Abstract: Acetylcholinesterase (AChE) is found both on the membranes of neuronal and non-neuronal cells. In this study we performed intravenous administrations of velnacrine (VLN) and acetylcholine (ACh), respectively, AChE inhibitor and substrate, in an animal model of lipopolysaccharide (LPS)-induced inflammation in Wistar rats. Using intravital microscopy the number of rolling and adherent leukocytes in post-capillary venules was monitorized and blood samples were collected for TNF-α plasma concentrations determination. Our results showed that in presence of LPS, ACh has an anti-inflammatory effect, seen by a decrease in TNF-α plasma levels and maintains the number of rolling and adherent leukocytes. The presence of …VLN before LPS almost blocked the LPS-induced rolling and TNF-α releasing. Thereby VLN seems to have, like ACh, an anti-inflammatory effect by diminishing TNF-α concentrations. Show more

Keywords: Inflammation, acetylcholine, TNF-α, velnacrine, rolling leukocytes, intravital microscopy

DOI: 10.3233/CH-121646

Citation: Clinical Hemorheology and Microcirculation, vol. 53, no. 1-2, pp. 209-216, 2013