Clinical Hemorheology and Microcirculation - Volume 49, issue 1-4

Authors: Brun, Jean-Frédéric | Varlet-Marie, Emmanuelle | Cassan, Delphine | Raynaud de Mauverger, Eric

Article Type: Research Article

Abstract: Athletes involved in rugby are characterized by a very specific pattern of body composition with an unusually important muscle mass. In a preceding study about rugbymen we evidenced that they exhibit a correlation between red blood cell aggregability and the amount of body fat although it remains within a normal range, and that red cell rigidity was correlated to isometric adductor strength. We had the opportunity of studying the relationships among exercise performance, body composition and hemorheology in 19 female rugby players (age 19–26, mean: 24.47 ± 0.67 yr) practising 4 – 10 hr/wk (mean 7.15 ± 0.3) since 1–12 …yr (mean 4,05 ± 0,694). VO2max was not related by its own to blood rheology, either hematocrit (r = −0.0717 p = 0.7706) or plasma viscosity (r = 0.0144; p = 0.9533), but other markers of performance exhivited a correlation with red cell rheology. Relationships between fitness and body composition were evidenced. Isometric handgrip strength was negatively correlated to red blood cell aggregability (Myrenne M, r = −0.57839; p = 0.00948 M1 r = −0.58910; p = 0.00795). Adductor isometric strength was negatively correlated to red blood cell aggregability Myrenne M (r = −0.5033; p = 0.0280) but not to M1 (r = −0.4227; p = 0.0714). Fat mass is a major determinant of the maximal oxygen consumption VO2max either measured by a field test (r = −0.766; p = 0.00013) or exercise test (r = −0.575; p = 0.00994) and was also negatively correlated to both handgrip (r = −0.4918; p = 0.0325) and RBC aggregability M (r = −0.57839; p = 0.00948 and M1 r = −0.5891; p = 0.00795). Independently of fat mass, FFM appears to be a determinant of blood viscosity (r = 0.4622; p = 0.0463) due to its correlation with RBC rigidity (r = 0.4781; p = 0.0384). Thus, trained young women exercising 4–10 hr/wk and thus exhibiting a low percentage of body fat exhibit clear relationships between body composition and hemorheology, but fat mass being low, the parameter correlated with blood rheology is in this case fat-free mass, consistent with recent findings indicating that high fat mass in women is sometimes correlated with parameters of the metabolic syndrome such as insulin resistance or inflammation. In addition, parameters quantifying fatness even within such a physiological range are in this sample negatively related with exercise performance. Show more

Keywords: Rugby, exercise, fat mass, hematocrit, blood viscosity, plasma viscosity, hemorheology, erythrocyte aggregation

DOI: 10.3233/CH-2011-1470

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 207-214, 2011

Authors: Brun, Jean-Frédéric | Varlet-Marie, Emmanuelle | Fédou, Christine | Raynaud de Mauverger, Eric

Article Type: Research Article

Abstract: Aerobic capacity and performance are associated with increased blood fluidity, while sedentarity leads to decreased exercise performance, and blood hyperviscosity. We aimed at investigating the relationships among body composition, blood rheology and exercise performance in this situation. In 46 sedentary subjects (53.09 ± 1.79 yr old; BMI = 32,35 ± 0,80) attending our unit for an exercise prescription we performed an exercise test to assess aerobic capacity, together with blood lipid profile and blood viscosity (MT 90 viscometer, Myrenne erythroaggregometer). The maximal aerobic capacity VO2max was not correlated to blood rheology but its changes were negatively correlated to those …of plasma viscosity (r = −0.679) and pre-training VO2max values were negatively correlated to the BMI (r = −0.45873; p = 0.00430) and fatness (waist circumference r = −0.53476; p = 0.00406). Hemorheological parameters were as expected correlated to blood lipids. The main determinant of the RBC rigidity index Tk was HDL-cholesterol (r = −0.70026; p = 0.00121). The main determinant of M1 is HDL-cholesterol (r = −0.5157; p = 0.0238). RBC aggregability “M” is negatively correlated to total cholesterol (r = −0.758932; p = 0.000105); HDL-cholesterol (r = −0.62232; p = 0.00444); LDL-cholesterol (r = −0.64486; p = 0.00386). Whole blood viscosity is correlated to triglycerides (r = 0.8569; p = 0.00000140) and negatively correlated to HDL-cholesterol (r = −0.5622; p = 0.0122). Waist circumference (an index of abdominal fatness) is correlated to blood viscosity (r = 0.597; p = 0.00888). The waist to hip ratio is correlated to Hct (r = 0.70075 p = 0.00120) and to blood viscosity (r = 0.8124334; p = 0.0000420). Fat-free mass is correlated to blood viscosity (r = 0.66528; p = 0.00137) and hematocrit (r = 0.64350; p = 0.00220). Hip circumference is negatively correlated to plasma viscosity (r = −0.5007; p = 0.0290). Therefore, this study confirms that hemorheological parameters are influenced by blood lipids, that changes in plasma viscosity are correlated to those of aerobic capacity, and that abdominal fat mass is associated with a worsening of blood rheology and of exercise performance. By contrast, gluteal fat (a factor associated with favorable lipid profile and high insulin sensitivity) is associated with a decrease in plasma viscosity, and fat-free mass is associated with higher blood viscosity and hematocrit, consistent with recent literature linking its size in abdominal obesity with a deleterious metabolic profile. Show more

Keywords: Metabolic syndrome, body fluids, hematocrit, blood viscosity, plasma viscosity, hemorheology, erythrocyte aggregation, fat mass, fat-free mass, gluteal fat

DOI: 10.3233/CH-2011-1471

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 215-223, 2011

Authors: Varlet-Marie, Emmanuelle | Brun, Jean-Frédéric | Fédou, Christine | Raynaud de Mauverger, Eric

Article Type: Research Article

Abstract: The aim of this study was to assess on a large series of soccer players our previous reports on blood rheology and exercise performance. In 99 soccer players (Age 24,17 ± 0,42 yr; weight 75,87 ± 0,89 kg; VO2 max 46,86 ± 0,95 mL/min/kg) an exercise test was performed for measuring maximal aerobic capacity and we measured blood viscosity at high shear rate (MT90 viscometer) and RBC aggregation (Myrenne MK1). The French questionnaire developped by the consensus group on overtraining of the French Society of Sports Medicine (SFMS) was also employed. The only hemorheologic statistical determinant of VO2 max was …hematocrit (Hct r = −0.2439; p = 0.0303). The lactate threshold 2 mmol/l was negatively correlated to M1 (r = −0.43224; p = 0.00847). There was a borderline correlation between the overtraining score at the questionnaire of the SFMS and plasma viscosity (r = 0.3080; p = 0.0532). Therefore, our study confirms that aerobic capacity in this sport is negatively correlated to hematocrit, that RBC aggregation is positively associated with blood lactate accumulation in blood during exercise, and that plasma viscosity is one of the parameters that increase when the athlete is on the edge of the overtraining syndrome. These data are consistent with previous reports about soccer players but caution is needed to extrapolate to other sports. Show more

Keywords: Exercise, soccer, overtraining, hematocrit, blood viscosity, plasma viscosity, hemorheology, erythrocyte aggregation

DOI: 10.3233/CH-2011-1472

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 225-230, 2011

Authors: Simmonds, Michael J. | Tripette, Julien | Sabapathy, Surendran | Marshall-Gradisnik, Sonya M. | Connes, Philippe

Article Type: Research Article

Abstract: Background: The principal determinants of oxygen uptake ($\Vdot$O2 ) kinetics are controversial, with dynamic changes in central and peripheral factors mediating oxygen supply and utilisation suggested to be limiting. The aim of this study was to determine whether important parameters of blood rheology were related to the exercise-induced time-course changes in $\Vdot$O2 and cardiac output ($\Qdot$c), or steady-state arteriovenous oxygen difference (a-vO2 D) during submaximal cycling. Methods and Results: Blood was collected from ten healthy, recreationally active males and females (age: 21.7 ± 1.3 yr; body mass index: 22.7 ± 2.0 kg·m−2 ), before each subject cycled at 105% …of the first ventilatory threshold. Red blood cell aggregation was negatively correlated with steady-state $\Vdot$O2 during exercise and the a-vO2 D at rest (r = −0.73, p < 0.05), and positively correlated to $\Qdot$c at rest (r = 0.71, p < 0.05). Blood viscosity at various shear rates was negatively correlated with the time constant of $\Vdot$O2 (all p < 0.01) on-transient kinetics. Red blood cell deformability at various shear stress was positively correlated to the time constant of $\Vdot$O2 (all p < 0.05) on-transient kinetics. Conclusions: The findings of the present study suggest that the rheological properties of blood may modulate, at least in part, the rate of change in the uptake and/or utilisation of oxygen at the onset of exercise. Show more

Keywords: Aggregation, blood viscosity, deformability, oxygen uptake kinetics, red blood cell

DOI: 10.3233/CH-2011-1473

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 231-241, 2011

Authors: Jung, F. | Leithäuser, B. | Sternitzky, R. | Mrowietz, C. | Pindur, G.

Article Type: Research Article

Abstract: Background: Endothelial cells secrete different mediators depending on biochemical and/or biophysical conditions, which can lead to vasodilation or vasoconstriction, respectively. Impaired endothelial responsiveness to specific vasodilator stimuli has been used as a surrogate marker of cardiovascular risk. Multiple methods allow testing endothelial responses in both microvessels and conduit arteries, but it is still unclear whether there is a relationship in endothelial function between these two different vascular beds. Material and methods: In order to examine, whether such macrocirculatory data might correlate with data obtained in the supplied microvessels, a parallel investigation in the brachial artery (BA) and the supplied nailfold …capillaries was performed. The duration and amplitude of the postischemic hyperemia (stasis in the vasculature of the left arm using a blood pressure cuff for 3 minutes) were measured (ultrasound technique) and simultaneously the amplitude and duration of the postischemic hyperemia in ipsilateral nailfold capillaries (intravital capillaroscopy). Results: There was absolutely no correlation between the duration (n = 153, r = 0.076, p = 0.3493) of the diameter increase in the BA and in ipsilateral nailfold capillaries. Conclusion: The regulation of the cutaneous microcirculation did not follow diameter changes of the conduit artery (BA) but seems to be dominated by the precapillary arterioles. Show more

Keywords: Conduit artery, microcirculation, cutaneous capillaries, endothelial dysfunction

DOI: 10.3233/CH-2011-1474

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 243-250, 2011

Authors: Prantl, L. | Pfeifer, C. | Geis, S. | Gosau, M. | Jung, E.M.

Article Type: Research Article

Abstract: Purpose: Osteocutaneous free flaps (OFF) are widely used to reconstruct large bone defects in trauma and cancer surgery. Currently no monitoring method is available to detect blood circulation around and inside the bone after transplantation. Therefore we used for the first time contrast-enhanced high-resolution ultrasound (hrCEUS) to gain evidence for the microcirculation of the transplanted bone. Materials and methods: 15 patients transplanted with OFF because of large bone defects at different sites were examined postoperatively with hrCEUS with a high resolution linear probe (6–9 MHz, LOGIQ E9/GE) and a bolus injection of 2.4 ml of contrast agent (SonoVue® , Bracco, …Italy). Operation and examination were performed by either an experienced plastic surgeon or an experienced ultrasound examiner. Microcirculation of the periost and bone was analyzed in different regions of interest (ROIs) and quantitative microcirculation analysis was performed using time intension curve analysis (TIC). We further analyzed clinical outcome of the patients in respect to revision-surgery, necrosis of the OFF and flap survival as well as viability on standard x-rays 2 months after surgery. Results: The most representative parameter by TIC analysis of hrCEUS were the area under the curve (AUC) and the time to peak (Ttop). The AUC of the periost and central part of the bone showed a high correlation (Pearson's r = 0.831). Mean AUC for the periost was 163.92 dB ± 49.44 and for the central part of the bone 70.42 dB ± 25.33. The Ttop of the periosteal ROI was 33.04 sec. ± 6.71 and the bone ROI 41.01 sec. ± 9.24. There was a high correlation of the Ttop of the periost and bone (Pearson's r = 0.937). One revision had to be performed due to haematoma and microcirculation defect of the distal part of the transplanted bone graft which was detected early by hrCEUS and the distal part of the avital bone could be removed timely. Conclusion: For the first time we could show that hrCEUS is a reliable method to evaluate the viability of OFF. The AUC and Ttop seem to be a valuable parameter to detect the microcirculation around and inside the bone transplant. Show more

Keywords: Bone transplant, contrast-enhanced ultrasound, TIC analysis, microcirculation

DOI: 10.3233/CH-2011-1475

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 251-259, 2011

Authors: Damaske, Ana | Muxel, Selina | Fasola, Federica | Radmacher, Marie Christine | Schaefer, Sarina | Jabs, Alexander | Orphal, Dörte | Wild, Philipp | Parker, John D. | Fineschi, Massimo | Munzel, Thomas | Forconi, Sandro | Gori, Tommaso

Article Type: Research Article

Abstract: The slow coronary flow phenomenon (SCF), a condition described by the presence of inappropriate delay in the progression of intracoronary contrast during angiography in the absence of stenoses, has been shown in some patients presenting with chest pain. While several conditions leading to “secondary” slow flow are known, there are no definitive conclusions regarding the exact pathogenesis of “primary” SCF. The present paper outlines the mechanisms that may lead to SCF, emphasizing the role of hemorheological and vascular factors in the pathogenesis of this phenomenon. Small vessel dysfunction has been proposed in the pathogenesis of SCF since the first description …of this syndrome in 1972. Abnormalities in coronary microvascular function result from increased microvascular resistances and impaired endothelial release of vasoactive substances, especially in production and bioavailability of endothelium derived NO. Inflammatory conditions (increased levels of C-reactive protein, interleukin-6 and adhesion molecules) and metabolic abnormalities such as impaired glycemic control, hyperuricemia and elevated serum gamma-glutamyltransferase were also found to contribute to microvascular dysfunction in patients with SCF. New studies have also indicated that increased blood viscosity and one of its major determinants, erythrocyte aggregation, is associated with the SCF. Rheological variables play a role in the control of shear stress and contribute to blood flow velocity changes. Although platelets do not have a significant influence on blood viscosity, it has been demonstrated that they are involved in the development of SCF. Increased mean platelet volume (MPV), an indicator of platelet activation and platelet aggregability is also significantly higher in patients with SCF compared with patients with normal coronary flow. Show more

Keywords: Coronary slow flow, endothelial function, viscosity, hematocrit, platelets

DOI: 10.3233/CH-2011-1476

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 261-269, 2011

Authors: Abegunewardene, Nico | Schmidt, Kai-Helge | Vosseler, Markus | Kreitner, Karl-Friedrich | Schreiber, Laura M. | Lehr, Hans-Anton | Gori, Tommaso | Münzel, Thomas | Horstick, Georg

Article Type: Research Article

Abstract: Aims: The purpose of this study was to evaluate the effect of transient local myocardial gene transfer of iNOS on cardiac function in a large mammal animal model of heart failure induced by chronic ischemia. Methods: Chronic myocardial ischemia was induced using a minimally invasive model in 16 landrace pigs. Upon demonstration of heart failure, eight animals were treated with liposome-mediated iNOS-gene-transfer by local intramyocardial injection; eight animals received a sham procedure to serve as control. Results: The transmurality of late enhancement (control: 46.4%, iNOS: 35.9%; p < 0.05) was significantly decreased in the ischemic area in the iNOS-treated group. …Wall thickness at end-systole (6.8 mm vs. 5.9 mm, p < 0.001) and at end-diastole (5.4 mm vs. 4.2 mm, p < 0.001) were significantly higher in the therapy group. Additionally, the regional wall motion at the level of the ischemic region was 3.5 mm in the therapy group while it was significantly less (3.0 mm, p < 0.001) in the control group. Conclusions: Our findings demonstrate that transient iNOS overexpression potentially leads to a significant decrease of regional late enhancement with a positive effect on regional cardiac function in the ischemic area in a large animal model of postischemic heart failure. Show more

Keywords: iNOS, gene therapy, regional contractility, heart failure

DOI: 10.3233/CH-2011-1477

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 271-278, 2011

Authors: Lechler, Philipp | Klein, Silvan M. | Prantl, Lukas | Englert, Carsten | Renkawitz, Tobias | Grifka, Joachim

Article Type: Research Article

Abstract: Both, skeletal development and fracture healing depend on an orchestrated sequence of cellular growth and differentiation processes. Regional changes in tissue oxygen tension were proposed as key regulators of osteoblast proliferation and phenotype. Hypoxia results in the stabilization of hypoxia-inducible factor-1α (HIF-1α), thus influencing expression of a multitude of genes required for cellular adaptation. In the present study we dissected the effects of HIF-1α on cellular proliferation and gene expression of primary human osteoblasts. Primary human osteoblasts were studied by transfecting siRNA and plasmids coding for human HIF-1α. Gene expression was analyzed by western blot and quantitative PCR. Functional assays …were performed to study HIF-1α function, i.e. proliferation and cell cycle analysis. As previously reported exposure to hypoxia led to a stabilization of HIF-1α on protein level and resulted in reduced rates of proliferation and osteocalcin expression. Furthermore, the expression of the proproliferative gene survivin was significantly reduced (p < 0.01). Knock down of HIF-1α attenuated hypoxic downregulation of proliferation (p < 0.05), and osteocalcin (p < 0.05) as well as survivin (p < 0.05) expression significantly. Importantly, the isolated overexpression of HIF-1α impaired proliferative activity and led to significantly reduced rates of expression of osteocalcin (p < 0.05) and survivin (p < 0.01). The present study shows that HIF-1α might reduce proliferation and survivin expression in primary human osteoblasts independently from cellular hypoxia. Furthermore, HIF-1α promoted the loss of the characteristic osteoblastic marker, osteocalcin in vitro. These findings underline the important role of HIF-1α in bone physiology and pathophysiology. Modulating HIF-1α function in hypoxic environments could be of value for future therapeutic approaches. Show more

Keywords: Hypoxia, HIF-1alpha, osteoblast, proliferation, cell viability

DOI: 10.3233/CH-2011-1478

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 279-286, 2011

Authors: Luca, Mary Clare | Liuni, Andrew | Muxel, Selina | Münzel, Thomas | Forconi, Sandro | Gori, Tommaso | Parker, John D.

Article Type: Research Article

Abstract: Despite decades of research and thousands of experimental publications, acute preconditioning strategies have yet to be implemented in clinical practice. While some have attributed this to a failure of the experimental studies to mimic the clinical environment, others have suggested that acute preconditioning strategies themselves may possess physiological limitations. In particular, there is evidence to suggest a reduced efficacy of acute preconditioning in the aged heard and in disease states, such as diabetes, hypertension, hyperlipidemia, and atherosclerosis. In addition, pharmacologic agent commonly used in clinical practice, such as sulfonylureas and non-steroidal anti-inflammatory agents may interfere with acute preconditioning signaling pathways. …Such considerations may preclude the translation of acute preconditioning strategies to the clinical setting. This has led some to shift attention to alternate strategies of cardioprotection, one such strategy being the possibility of generating a prolonged state of cardioprotection. Although preliminary, studies to date have suggested that sustained preconditioning strategies may not be associated with the same drawbacks as acute preconditioning. Further, cardioprotective signaling pathways that elicit the sustained preconditioning response may be distinct from acute signaling pathways, which permit pharmacologic targeting of these pathways in the future. Additionally, sustained preconditioning strategies may be clinically applicable in the setting of acute myocardial infarction, a setting where acute preconditioning strategies are inherently limited. This review will briefly discuss the current data regarding sustained preconditioning strategies, including those in humans, and discuss the goal of future studies in this setting. Show more

DOI: 10.3233/CH-2011-1479

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 287-293, 2011

Authors: Tikhomirova, Irina A. | Oslyakova, Anna O. | Mikhailova, Svetlana G.

Article Type: Research Article

Abstract: We estimated hemorheological parameters of vein blood samples and cutaneous microvascular blood flow in patients with acute ischemic stroke and in controls. The worsened blood rheological properties were registered in patients with stroke: the enhanced whole blood viscosity was due to the substantial increase of plasma viscosity and the impairment of microrheological blood properties: elevated erythrocyte aggregability and decreased deformability compared to the healthy group. The decrease of oxygen consumption fixed by rheological methods and by laser Doppler flowmetry led us to conclude that the tissue hypoxia took place in patients with stroke. The regulatory mechanisms aimed to maintain blood …supply to tissue were activated under cerebral infarction and the impact of unfavorably changed rheological blood properties was markedly enhanced. Revealed close interrelations between rheological and microcirculation parameters testified the important role of hemorheological factors in maintenance of microvascular blood flow and oxygen delivery to tissue. Show more

Keywords: Microcirculation, hemorheology, stroke, regulatory mechanisms

DOI: 10.3233/CH-2011-1480

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 295-305, 2011

Authors: Reinhart, W.H. | Geissmann-Ott, C. | Bogdanova, A.

Article Type: Research Article

Abstract: Purpose: Red blood cells (RBCs) express N-methyl D-aspartate (NMDA) receptors on their surface. We tested if NMDA receptor activation or inhibition had an influence on RBC deformability and aggregability. Methods: Heparinized blood was drawn from healthy volunteers and centrifuged. RBCs were washed twice and resuspended with a hematocrit of 30% in a same buffer solution containing 3% dextran 70. Aliquots were prepared: a) control; b) containing 100 μM homocysteic acid (NMDA receptor agonist); c) 100 μM memantine (NMDA receptor inhibitor) and 100 μM homocysteic acid. RBC suspension viscometry (Contraves LS-30) was done at 37°C with shear rates of 37.6 s−1 …and 0.1 s−1 . RBC aggregability was assessed with a Myrenne aggrometer and sedimentation rate. Results: Neither NMDA receptor activation nor inhibition had an influence on biophysical properties of RBCs. RBC suspension viscosity at a shear rate of 37.6 s−1 was 3.62 ± 0.16, 3.61 ± 0.13, and 3.62 ± 0.16 mPa.s for control, homocysteic acid, and memantine + homocysteic acid, respectively, indicating an unchanged RBC deformability. The RBC aggregability parameters (low shear viscosity, Myrenne aggregometry at stasis (M) and 3 s−1 (M1 ), and the sedimentation rate) showed no influence of either memantine and/or homocysteic acid. A large interindividual variability in RBC aggregability was observed. A good correlation was found between M, M1 and sedimentation values, but not with low shear viscosity values. Conclusions: An activation or inhibition of NMDA receptors on RBCs has no influence on their deformability and aggregability. RBC aggregability varies largely among individuals, which was consistently detected by the sedimentation rate and the Myrenne aggregometer, but not by low shear viscosity, which should not be used for this purpose. Show more

DOI: 10.3233/CH-2011-1481

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 307-313, 2011

Authors: Ruef, P. | Ehrhard, M. | Frommhold, D. | Koch, L. | Fritzsching, B. | Poeschl, J.

Article Type: Research Article

Abstract: There are several reports demonstrating an involvement of bacterial toxins in the rigidity of red blood cells (RBC). The present study investigates the influence of E. coli F-583-Rd lipid A on RBC deformability under mechanical shear stress. Verapamil (Ca2+ channel inhibitor), staurosporine (protein kinase inhibitor) and Y-27632 (rho-kinase inhibitor) were used to modify the effect of lipid A on RBC deformability. We also determined if E. coli F-583-Rd Lipid A could induce an increase of intracellular Ca2+ concentration. For the deformation measurements RBC (10 adult donors) were incubated with E. coli F-583-Rd lipid A (100μg/ml) and also co-incubated …with either verapamil (10−7 mol/l), staurosporine (10−7 mol/l) or Y-27632 (10−7 mol/l). The deformation of the RBC under different shear stresses (0.6–60 Pa) was measured by a shear stress diffractometer (Rheodyne SSD). Intracellular Ca2+ was determinded by flow cytometry in RBC incubated with Lipid A and labeled with fluorescent Fluo-4/AM which binds intracellular Ca2+ with high affinity resulting in enhanced green fluorescence intensity. At increasing shear stresses Lipid A induced a significantly lower elongation. Co-incubation of the erythrocytes with verapamil or staurosporine inhibited lipid A induced decrease in elongation while Y-27632 had no effect. Verapamil, Staurosporine and Y-27632 did not influence the elongation response of the cells under control conditions. Lipid A induced a marked increase in fluorescence Fluo-4/AM indicating increased intracellular Ca2+ . These results suggest that E. coli F-583-Rd lipid A is able to influence red blood cell rigidity by a rapid and significant increase of intracellular Ca2+ concentration. Verapamil and staurosporine abolished the decrease in deformability of Lipid A incubated RBC. Show more

Keywords: Red blood cell, sepsis, lipid A, Ca$^{2+}$, deformability, staurosporine, verapamil, rho-kinase-inhibitor

DOI: 10.3233/CH-2011-1482

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 315-322, 2011

Authors: Fornal, Maria | Korbut, Renata A. | Grodzicki, Tomasz

Article Type: Research Article

Abstract: Relationship between erythrocyte deformability and: a) soluble cell adhesion molecules concentration, b) glomerular filtration rate (eGFR) has been investigated in three study groups: a group of 20 patients with diagnosed arterial hypertension, a group of 20 individuals with exclusively hypercholesterolemia and a group of 22 healthy persons. The individuals with hypertension or hypercholesterolemia were free of any other cardiovascular disease risk factor and were not on any therapy prior to entering the study. Clinical and laboratory data included systolic and diastolic blood pressure (obtained by ABPM), lipids profile, eGFR, red blood cell (RBC) deformability (assessed by shear stress laser diffractometry) …and levels of circulating soluble vascular adhesion molecules-1 (sVCAM-1) as well as soluble intracellular adhesion molecules-1 (sICAM-1). In the group of hypertensives, RBC deformability and concentration of circulating soluble adhesion molecules showed statistically significant negative correlations: RBC deformability decreases with increasing level of: a) sVCAM-1, R = −0.61, p < 0.002, b) sIVCAM-1, R = −0.53, p < 0.009. In parallel, statistically significant increase of eGFR was observed with rising erythrocyte deformability, R = 0.60, p < 0.005. In the groups of healthy individuals and patients with hypercholesterolemia there was no sign of any correlations between the considered parameters. The observed correlations suggest that in patients diagnosed exclusively with hypertension, firstly, erythrocyte deformability may serve as a marker of endothelial dysfunction and, secondly, red blood cells may be mediators of adverse changes in kidneys. Show more

Keywords: Erythrocyte deformability, glomerular filtration rate, soluble cell adhesion molecules, hypertension

DOI: 10.3233/CH-2011-1483

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 323-329, 2011

Authors: Papp, J. | Toth, A. | Sandor, B. | Kiss, R. | Rabai, M. | Kenyeres, P. | Juricskay, I. | Kesmarky, G. | Szabados, S. | Toth, K.

Article Type: Research Article

Abstract: Conditions during coronary artery bypass grafting (CABG) performed on beating heart (off-pump) are more physiological than using extracorporeal perfusion (on-pump). The present study aims to examine the hemorheological aspects of the two techniques. Blood samples were taken from patients undergoing on-pump (n = 25) and off-pump (n = 22) CABG, upon arrival to the operating theatre, after 20 and 40 minutes during the operation, after closing the thorax, on the 1st and 2nd postoperative days, and during the 2nd and 6th month control check-ups. Hematocrit (Hct), plasma and whole blood viscosity (PV, WBV; Hevimet 40 capillary viscometer), red blood cell …(RBC) aggregation (Myrenne RBC aggregometer, LORCA) and deformability (LORCA, Carat FT-1 filtrometer), and platelet aggregation (Carat TX4 aggregometer) were determined. The morphology of red blood cells was investigated by scanning electron microscopy (SEM). Hct, PV, WBV and RBC aggregation decreased significantly during the early phase of the surgery, they started to recover during the postoperative period, and reached the baseline values by the 2nd and 6th month control check-ups. These parameters were significantly lower in samples taken after 20 and 40 minutes in the on-pump group. SEM showed rather damaged and malformed cells in case of on-pump surgery. Ektacytometry showed no significant difference, but RBC deformability was impaired during on-pump surgery when measured by filtrometry. The decrease in platelet aggregation was more pronounced by the end of surgery in case of on-pump technique. During CABG rheological parameters change less when using the off-pump method, and mechanical damage of RBCs are also smaller. The off-pump technique seems to be favorable from a hemorhelogical point of view. Show more

Keywords: Coronary artery bypass grafting, on-pump, off-pump, viscosity, erythrocyte aggregation, erythrocyte deformability, platelet aggregation, scanning electron microscopy

DOI: 10.3233/CH-2011-1484

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 331-346, 2011

Authors: Wischke, Christian | Lendlein, Andreas

Article Type: Research Article

Abstract: Polymer-based biomaterials are extensively used in all disciplines of clinical medicine and innovations in biomaterial science are building a product pipeline, e.g., of future cardiovascular implants. Still, cardiovascular applications demand a number of extensive requirements of properties and functions to be fulfilled by the polymer matrix. This report provides an overview on some of these issues and how they can be addressed by a tailored design of novel polymer-based biomaterials. Multifunctional shape-memory polymers are highlighted as a class of materials that combine biocompatibility and the capability for stimuli-induced active movements for anchoring of implants with a controlled degradation and drug …release profile to enable a functional regeneration of the tissue at the application site. Show more

Keywords: Degradable biomaterial, cardiovascular implants, shape-memory polymers, stents, vascular prosthesis

DOI: 10.3233/CH-2011-1485

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 347-355, 2011

Authors: Song, Y. | Feijen, J. | Grijpma, D.W. | Poot, A.A.

Article Type: Research Article

Abstract: For the treatment of cardiovascular disease, functional arterial blood vessel prostheses with an inner diameter less than 6 mm are needed. This article gives an overview of the preparation of such vascular grafts by means of tissue engineering.

Keywords: Vascular graft, tissue engineering

DOI: 10.3233/CH-2011-1486

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 357-374, 2011

Authors: Braune, S. | Hönow, A. | Mrowietz, C. | Cui, J. | Kratz, K. | Hellwig, J. | Üzüm, C. | Klitzing, R.V. | Lendlein, A. | Jung, F.

Article Type: Research Article

Abstract: Small calibre vascular prostheses (<6 mm) still lack medium and long term patency. Inelasticity of the prosthesis is one of the characteristics, which is involved in the mechanisms of failure (e.g. the development of neointimal hyperplasia at the distal anastomosis). Here we report about covalently crosslinked poly(n-butyl acrylate) networks (cPnBA) with adjustable elastic moduli, which can be tailored to values of human arteries (between 100 and 1000 kPa). Motivated by the potential application of such polymer networks as cardiovascular prosthesis, adhesion, activation and thrombus formation of human platelets on cPnBA networks were evaluated. All cPnBA-samples displayed a high thrombogenicity compared …to the control (silicone). Significantly less platelets adhered on the surface of the soft cPnBA04 than on cPnBA73. All cPnBA samples displayed a higher number of platelet aggregates and a lower number of inactivated platelets in comparison to the control. While the elastic modulus of cPnBA networks could be successfully adjusted to that of human arteries, the tested polymers did not show an optimal hemocompatibility. Future studies aim at improving the biofunctionality by surface modification of these polymer networks. Show more

Keywords: Haemocompatibility, platelets, polymer networks, elastic modulus, biomaterial

DOI: 10.3233/CH-2011-1487

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 375-390, 2011

Authors: Dreyer, Lutz | Krolitzki, Benjamin | Autschbach, Rüdiger | Vogt, Peter | Welte, Tobias | Ngezahayo, Anaclet | Glasmacher, Birgit

Article Type: Research Article

Abstract: Endothelial cells (ECs) are permanently exposed to the blood flow and the resulting shear stress, its magnitude varying with the EC site in the blood stream. Along with other mechanical stimuli like vessel wall stretching or hydrostatic blood pressure, this shear stress modulates the endothelial cell function, morphology and gene expression. Here, we describe our improved cone-and-plate reactor that applies up to 10 dyn/cm2 uniform wall shear stress on a defined, ring-shaped region on a culture dish. At the same time, a hydrostatic pressure of up to 195 mmHg can be applied by increasing the atmospheric pressure in the …incubator box. Gas composition can be controlled additionally, used for maintaining CO2 -homeostasis or inducing hypoxic conditions. For better comparability, six cone-and-plate systems can be used at the same time at different rotational velocities. The effects on cell morphology, cytoskeleton and cell alignment can be monitored during application using a laser scanning microscope. Flow conditions have been studied and a sufficient area of uniform wall shear stress could be shown. To exceed 10 dyn/cm2 , we suggest an increase in medium viscosity. Show more

Keywords: shear force, cone-and-plate rheometer, mechanotransduction, endothelial cells

DOI: 10.3233/CH-2011-1488

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 391-397, 2011

Authors: Wenzel, Folker | Gettmann, Thorben | Zimmermann, Norbert | Giers, Günther

Article Type: Research Article

Abstract: Introduction: The hormones erythropoietin (EPO) and thrombopoietin (TPO) are main regulators of erythro- and thrombopoiesis. Cell loss caused by operative procedures may alter serum levels of the hormones, resulting in well known phenomenons like reactice thrombocytosis. Material and methods: Blood samples from 10 patients (mean age 63 ± 9 years) were obtained before and at day 1, 5 and 10 after coronary artery bypass grafting (CABG). EPO and TPO levels were determined by commercially available ELISA-Kits (R&D Systems, Germany). In addition, platelet count (PC) and hemoglobin concentration (Hb) were determined. Results: Prior to CABG, EPO (13.2 ± 8.2 mU/mL), TPO …(189 ± 52 pg/mL), Hb (8.8 ± 1.1 mmol/L) and PC (254 ± 121/nL) were within a normal range. At day 1 after surgery, Hb and PC were significantly decreased to 6.6 ± 0.9 mmol/L and 138 ± 70/nL. In contrast, EPO and TPO were significantly elevated to 32 ± 18 mU/mL and 336 ± 96 pg/mL, respectively, in spite of hemodilution. In particular, TPO elevation was followed by a significant increase in PC (342 ± 144/nL) at day 10 after surgery compared to preoperative values. Conclusions: Appropriate to the decrease in hemoglobin concentration and platelet count, clear alterations of serum erythropoietin and thrombopoietin levels could postoperatively be observed. EPO levels showed an inverse correlation to hemoglobin concentrations, whereas a disturbed thrombopoietin feedback mechanism resulted in the phenomenon of reactive thrombocytosis. Show more

DOI: 10.3233/CH-2011-1489

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 399-406, 2011

Authors: de Almeida, J.P. Lopes | Freitas-Santos, T. | Saldanha, C.

Article Type: Research Article

Abstract: Recent evidence has shown that plasma fibrinogen, a major cardiovascular risk factor, interacts with the erythrocyte membrane and acts to influence blood flow via erythrocyte nitric oxide (NO) modulation. In the present pioneer in-vitro study, whole blood samples were harvested from healthy subjects and aliquots were incubated in the absence (control aliquots) and presence of fibrinogen at different degrees of band 3 phosphorylation, and the levels of NO, nitrite, nitrate and S-nitroglutathione (GSNO) were determined. Hyperfibrinogenemia interferes with erythrocyte NO mobilization without changing its efflux in a way that seems to be dependent of the degree of band 3 phosphorylation. …In presence of higher fibrinogen concentrations the NO efflux is reinforced when band 3 is phosphorylated (p < 0.001). Higher levels of nitrite, nitrate and GSNO were documented (p < 0.05). However, the mechanisms by which fibrinogen signalling modulates erythrocyte function remain to be clarified and are currently under study. These conditions may be considered an approach to be followed in blood storage for transfusions. Show more

Keywords: Band 3 protein, erythrocyte, fibrinogen, nitric oxide, nitrates, nitrites, S-nitrosoglutathione

DOI: 10.3233/CH-2011-1490

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 407-416, 2011

Authors: Gluhcheva, Y. | Ivanov, I. | Atanasov, V. | Antonova, N. | Ivanova, Ju. | Mitewa, M.

Article Type: Research Article

Abstract: The study evaluated the affect of chronic cadmium (Cd) and monensin treatment on some hematological parameters and its relationship with the rheological variables. Adult male mice were subjected to chronic treatment with cadmium acetate [Cd(CH3 COO)2 × 2H2 O] (group 1), Cd(CH3 COO)2 × 2H2 O followed by treatment with low dose monensin (group 2) and Cd(CH3 COO)2 × 2H2 O followed by high dose monensin treatment (group 3). Cd(CH3 COO)2 × 2H2 O and deprotonated monensin were dissolved in distilled water and given daily to the experimental animals. Mice drinking distilled water served as a …control group (group 4). Hematological parameters and erythrocyte morphology were evaluated in parallel with whole blood viscosity (WBV). Cd treatment reduced Hb and increased RDW. The addition of high dose monensin significantly improved erythrocytic indices compared to the control. Erythrocyte anisocytosis was observed in blood smears of Cd-treated mice corresponding to the increased RDW. WBV was significantly elevated in the experimental groups in the whole range of shear rates compared to the control group and in groups 2 and 3 was lower than in group 1 but remained higher compared to group 4. Correlations were found between WBV and RBC, Hb, Hct, MCV and RDW. The results suggest that hemorheological parameters such as WBV should be monitored in parallel with the hematological parameters when monensin is applied and heavy metal intoxication is suspected. Show more

Keywords: Cadmium, hematological indices, whole blood viscosity, monensin

DOI: 10.3233/CH-2011-1491

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 417-422, 2011

Authors: Mayer, A. | Hiebl, B. | Lendlein, A. | Jung, F.

Article Type: Research Article

Abstract: So called intermediate (MO2) monocytes/macrophages possess anti-inflammatory properties and express the MO lineage marker CD163. On a hydrophilic, acrylamide-based hydrogel human intermediate (CD14++ CD16+ ) CD163++ monocytes/macrophages (aMO2) which were angiogenically stimulated, maintained a pro-angiogenic and non-inflammatory status for at least 14 days. Here we explored, whether this aMO2 subset can positively influence the proliferation of human umbilical venous endothelial cells (HUVECs) without switching back into a pro-inflammatory (MO1) phenotype. aMO2 or HUVEC were seeded alone on glass cover slips (0.5 × 105 cells / 1.33 cm2 ) in a HUVEC specific cell culture medium (EGM-2) for …3 hrs, 24 hrs and 72 hrs or under co-culture conditions (0.5 × 105 HUVEC + 0.25 × 105 aMO2 / 1.33 cm2 ) in EGM-2 for the same time window as well (n = 6 each). Under co-culture conditions the numbers of adherent HUVEC per unit area were significantly higher (p < 0.01; 525 ± 52 HUVEC/mm2 ) compared to control mono-cultures (473 ± 76 HUVEC/mm2 ) after 72 hrs of cultivation and showed their typically spread morphology. The aMO2 remained in their subset status and secreted VEGF-A165 without release of pro-inflammatory cytokines until the end of the 72 hrs cultivation time period, thereby supporting the HUVEC proliferation. These in vitro results might indicate that this MO subset can be used as cellular delivery system for pro-angiogenic and non-inflammatory mediators to support the endothelialisation of biomaterials like e.g. cPnBA. Show more

DOI: 10.3233/CH-2011-1492

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 423-430, 2011

Authors: Muravyov, Alexei V. | Bulaeva, Svetlana V. | Tikhomirova, Irina A. | Zamishlayev, Andrey V. | Uzikova, Ekaterina V. | Miloradov, Mikhail Ju.

Article Type: Research Article

Abstract: This study was designed to evaluate hemorheological changes in patients with cerebrovascular disease (CVD) and peripheral arterial disease (PAD) after 4 weeks of pentoxifylline therapy as well as to study red blood cell microrheological variables after the cell incubation with pentoxifylline and some phosphodiesterase (PDE) activity inhibitors. The patients with CVD (n = 50) and PAD (n = 33) were treated with pentoxifylline (400 mg, thrice a day) for 4 weeks. Before and after drug therapy the hemorheological measurements including plasma and whole blood viscosity, red blood cell aggregation (RBCA) and deformability (RBCD) were completed. In vitro study RBCs were …incubated with: 1) Vinpocetine – inhibitor PDE-1, 10 μM; 2) Rolipram – PDE-4, 10 μM; 3) Isobutyl-methylxanthine (IBMX) – nonselective PDE inhibitor, 100 μM and with pentoxifylline, 10 μM The cell incubation was performed at 37°C for 15 min. There were the positive changes of hemorheological profile after 4 weeks of the pentoxifylline therapy both in CVD and PAD patients. The marked RBCD changes were observed after the in vitro cell pentoxifylline treatment as well. Perhaps it is connected with the inhibition of the phosphodiesterase activity in RBCs. An application of drugs and chemicals that can inhibit the PDE activity resulted in RBCD rise and RBCA decrease. The experiments with the use of selective PDE inhibitors have revealed the similar red cell deformability changes. Vinpocetine increased RBCD significantly (p < 0.05). PDE-4 inhibitor – Rolipram stimulated RBCD by 15% (p < 0.05). Some more effective was IBMX. After cell incubation with it a significant rise of the deformability (by 27%; p < 0.05) was found. All drugs, having PDE activity decreased RBCA, but the most pronounced effect had Vinpocetine (50%; p < 0.05). Thus, administered pentoxifylline, daily (1200 mg), during four weeks improves hemorheological profile and especially its microrheological part as well as the blood transport capacity in subjects with cerebral and peripheral vascular disorders. It is most probably red cell microrheological control mechanisms may be associated with the phosphodiesterase activity alterations. Show more

Keywords: Cerebrovascular and peripheral arterial disease, blood viscosity, red blood cells deformability and aggregation, hemorheological profile, phosphodiesterase, pentoxifylline

DOI: 10.3233/CH-2011-1493

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 431-439, 2011

Authors: Antonova, N. | Riha, P. | Ivanov, I. | Gluhcheva, Y.

Article Type: Research Article

Abstract: Mechanical and electrical properties of the normal RBCs suspensions and of hardened after treatment with glutaraldehyde (0.01–2.5%) RBCs in isotonic physiological solution and Dextran 70 000 (Dextran 70) and Polyethylene glycol 35 000 (PEG) and adjusted to hematocrit of 40%, were evaluated. Apparent viscosity and conductivity were measured under steady and transient flow regimes at low shear rates and at different local structure of the flow at 37°C. A time course of conductivity was recorded in parallel with the rheological properties of the RBC suspensions and conductivity and apparent viscosity dependences on shear rates were studied and compared at different …concentrations of Dextran 70, PEG and glutaraldehyde. Low shear viscosity decreased after RBCs treatment with glutaraldehyde and at 0.5–2.5% it is constant. Echinocytes are observed at low Dextran 70 and PEG concentrations while spherocytes are found mainly in smears treated with higher concentrations. The results show that the apparent viscosity and conductivity of RBCs suspensions in Dextran 70 and PEG are strongly influenced by flow, shear rates, concentration, cell deformability and morphology and the method is sensitive to study the mechanical and electrical properties of RBC suspension and to provide experimental description of RBCs and other cell-to-cell interactions. Show more

Keywords: RBC suspensions, viscosity, conductivity, morphology, glutaraldehyde, Dextran 70 000, Polyethylene glycol 35 000 (PEG)

DOI: 10.3233/CH-2011-1494

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 441-450, 2011

Authors: Reinhart, W.H. | Schulzki, T.

Article Type: Research Article

Abstract: We studied the influence of metabolic depletion on red blood cell (RBC) aggregability, which is a determinant of blood flow. Heparinized blood was stored at room temperature for 0, 24, and 48 h. RBCs were washed twice and resuspended in Tris-buffer containing 3% dextran 70 (hematocrit 30%). Suspension viscosities were measured at 37°C and shear rates of 37.6 and 0.1 s−1 , RBC aggregability was analysed by the sedimentation rate, direct microscopic visualization and a Myrenne aggregometer. RBCs in autologous plasma showed an increasing echinocytic shape transformation, which was reversible in buffer. The viscosities of RBC suspensions in buffer remained …unchanged at both low (0.1 s−1 ) and high shear rate (37.6 s−1 ), the latter result indicating an unchanged RBC deformability. RBC aggregability decreased: The RBC sedimentation rates were 40.7 ± 5.0, 29.3 ± 13.4, and 13.3 ± 11.2 mm/h (p < 0.001) at 0, 24, and 48 h, respectively, which correlated well with the visual aggregability index and the Myrenne aggregation parameters M and M1 . We conclude that metabolic depletion for 48 h leads to RBC swelling and a reversible echinocytic shape transformation. These ATP-depleted, but normally shaped RBCs had a decreased aggregability. In contrast to all other methods used, low shear viscosity was inaccurate and should not be used to test RBC aggregability. Show more

Keywords: Aggregation, ATP, erythrocyte, morphology, viscosity

DOI: 10.3233/CH-2011-1495

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 451-461, 2011

Authors: Saldanha, C. | de Almeida, J.P. Lopes

Article Type: Research Article

Abstract: We review the major hemorheological experimental studies that show the erythrocyte aggregation as a link between basic and clinical research. The results of the clinical cross-sectional and longitudinal studies presented here will highlight the possible association between erythrocyte aggregation and plasma fibrinogen. Basic studies conducted in vitro are also mentioned as for its relevance in answering questions raised in clinical settings, as well as and in understanding the underlying influent factors in the erythrocyte tendency to aggregate and disaggregate.

DOI: 10.3233/CH-2011-1496

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 463-472, 2011

Authors: Sievers, Henrieke | Bahramsoltani, Mahtab | Käßmeyer, Sabine | Plendl, Johanna

Article Type: Research Article

Abstract: Human microvascular endothelial cells derived from myocardium (HCMEC), lung (HPMEC) and foreskin (HDMEC) showed different angiogenic potency when cultivated in their original growth media provided by the distributors. In order to standardize microenvironmental conditions in an all-in-one assay of angiogenesis the aim of this study was to find one optimal growth medium for the endothelial cells derived from the different organs. Therefore each endothelial cell type was cultivated under identical conditions in the different original growth media as well as in several media formulations of the original growth media. Results reveal that even if cultivated in the same growth medium …under exactly the same cultivation conditions – over a prolonged time period of 60 days – the endothelial cells still showed different angiogenic potency. This is due to a combination of extrinsic factors, i.e. the isolation procedure and in particular the growth medium, as well as to intrinsic differences between cells of diverse origin. Show more

Keywords: Human microvascular endothelial cells, myocardium, lung, foreskin, angiogenic potency, growth medium

DOI: 10.3233/CH-2011-1497

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 473-486, 2011

Authors: Forconi, Sandro | Wild, Philip | Munzel, Thomas | Gori, Tommaso

Article Type: Research Article

Abstract: The role of viscosity, and of interindividual variations in this parameter, in the pathophysiology of cardiovascular disease remain incompletely understood. Any speculation regarding the possible impact of “hemorheological” therapies is therefore even more complex. In the last years, the debate regarding the relationship between increased viscosity and atherogenesis has been opened again. While the traditional view postulates that an increased blood viscosity has invariably a negative impact on tissue perfusion and therefore should be considered as a risk factor (when not as a true disease), a more recent hypothesis has been formulated based on the observation that small increases in …viscosity actually have vasodilatory effects, potentially improving tissue perfusion. Show more

Keywords: Coronary slow flow, endothelial function, viscosity, hematocrit, platelets

DOI: 10.3233/CH-2011-1498

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 487-491, 2011

Authors: Vayá, Amparo | Hernández-Mijares, Antonio | Bonet, Elena | Sendra, Rosa | Solá, Eva | Pérez, Rafael | Corella, Dolores | Laiz, Begoña

Article Type: Research Article

Abstract: The contribution of hemorheological alterations in the prothrombotic condition in patients with metabolic syndrome (MS) remains a question of debate. We aimed to determine the association between MS and hemorheological parameters by means of a case-control study in 61 MS patients and 89 controls without MS. We determined blood viscosity at 230 s−1 (Brookfield DVIII viscosimeter); plasma viscosity (Fresenius capillary plasma viscosimeter); erythrocyte aggregation at stasis and 3 s−1 (MA-1 erythrocyte aggregometer); erythrocyte deformability (Rheodyn SSD at shear stresses of 12, 30 and 60 Pascals) and fibrinogen, along with anthropometric, lipidic and inflammatory parameters. MS patients showed increased …blood viscosity (p = 0.018), plasma viscosity (p < 0.001), fibrinogen (p < 0.001), erythrocyte aggregation (p < 0.001), and decreased erythrocyte deformability (p = 0.033). In the multivariate regression analysis, fibrinogen and triglycerides predicted plasma viscosity and erythrocyte aggregability, whereas erythrocyte deformability was associated with alterations in the hydrocarbonate metabolism. Blood viscosity related to abdominal obesity. The logistic regression analysis revealed that of all the MS components, only hypertriglyceridemia independently predicts plasma hyperviscosity (OR 3.75 CI 1.44–9.77 p = 0.007) and erythrocyte hyperaggregability (OR 2.41 CI 1.00–5.80 p = 0.050). Erythrocyte hyperaggregability (EA > 8.23) and hyperfibrinogenemia (fibrinogen > 358 mg/dL) were independent predictors of MS: OR 3.34, 95% CI 1.40–7.93, p = 0.006 and OR 2.42 95% CI 1.04–5.66, p = 0.041, respectively. We conclude that MS is associated with an altered hemorheological profile related to inflammatory, lipidic and glucose intolerance parameters which could favor the development of thrombo-embolic and athero-thrombotic events in MS patients. Show more

DOI: 10.3233/CH-2011-1499

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 493-503, 2011

Authors: Velcheva, Irena | Damianov, Petar | Antonova, Nadia | Stoyneva, Zlatka | Mantarova, Stefka | Dimitrova, Valentina

Article Type: Research Article

Abstract: The study aimed to investigate the hemorheological parameters in patients with diabetes mellitus type 2 and to estimate their relationship with the cerebral and cutaneous blood flow and their responses to postural changes. The basic hemorheological constituents: hematocrit (Ht), fibrinogen (Fib), whole blood (WBV) and plasma viscosity (PV) were examined in 20 patients with diabetes mellitus type 2 and in 10 healthy age and sex matched controls. Blood flow velocity in the middle cerebral artery (MCA) was measured by transcranial Doppler monitoring at rest and during 5-min head-up tilt. Also laser Doppler-recorded tiptoe skin blood flow was investigated and venoarteriolar …reflex perfusion responses to postural impact was monitored. Significant increase of Fib and WBV at shear rates of 0.0237 s−1 to 128.5 s−1 in the patients in comparison to controls was found. The postural challenge caused decrease of the cerebral blood flow velocity and increase of the resistance index (RI) in the diabetic patients. The initial mean skin perfusion values of the tiptoes and the venoarteriolar constriction response indices were significantly higher in the diabetes group. In the patients with diabetes mellitus type 2 the increased blood viscosity values were associated with impaired cerebrovascular and peripheral vascular responces. Show more

Keywords: type 2 diabetes mellitus, hemorheological parameters, transcranial Doppler, head-up tilt, laser Doppler flowmetry, venoarteriolar reflex

DOI: 10.3233/CH-2011-1501

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 505-511, 2011

Authors: Velcheva, Irena | Damianov, Petar | Mantarova, Stefka | Antonova, Nadia

Article Type: Research Article

Abstract: Our study aimed to investigate the relationship between hemorheological parameters and heart rate variability (HRV) in patients with diabetes mellitus type 2. Hemorheological variables, including hematocrit (Ht), fibrinogen (Fib), whole blood (WBV) and plasma viscosity (PV) at shear rates of 0.0237 s−1 to 128.5 s−1 were examined in 20 patients with diabetes mellitus type 2 and in 10 control subjects. They all underwent non-invasive short-term monitoring of heart rate at rest and after passive head-up tilt. Measurement of the R-R intervals and calculation of the time domain parameters and the power spectral data were performed by our softwear, …using fast Fourier transformation. Significant increase of Fib and WBV in the patients in comparison to controls was found within the range of shear rates 0.0237 s−1 to 128.5 s−1 . In the diabetic patients parallel decrease of the total power (TP), the low frequency spectral power (LF) and of the mean RR and mild increase of the low frequency-high frequency ratio (LF/HF) at rest were established. This tendency was kept after the passive tilt. In patients with diabetes mellitus type 2 the increased blood viscosity was associated with reduced HRV. Show more

Keywords: type 2 diabetes, hemorheological parameters, heart rate variability

DOI: 10.3233/CH-2011-1500

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 513-518, 2011

Authors: Gehmert, Sanga | Gehmert, Sebastian | Bai, Xiaowen | Klein, Silvan | Ortmann, Olaf | Prantl, Lukas

Article Type: Research Article

Abstract: MSCs reside within their niche and pathologic conditions such as hypoxia and inflammation can lead to mobilization and migration of Mesenchymal Stem Cells (MSCs). Xenograft animal models using immundeficient mouse demonstrated that MSCs migrated to and distributed throughout the tumors and were found to engraft into tumor stroma and vasculature. In contrast, MSCs primarily incorporated within tumor-capsula and did not invade the tumor using immuncompetent tumor allograft models. Here we hypothesize that MSCs migrate primarily towards an inflammatory milieu independent of the underlying biological process causing the inflammation. Murine MSCs (mASCs) were isolated from subcutaneous fat tissues and transduced at …passage 0 with lentiviral vector encoding green fluorescent protein (GFP) and luciferase reporter. Breast cancer was established in BALB/c mice by subcutaneous injection of 4T1 cells into the left mammary fat pad. E. coli were injected subcutaneously in the right 4th mammary fat pad. After 24 h luciferase labeled mASCs were administered intraperitoneal (i.p.) and monitored with IVIS Bioluminescence camera for 72 hours. Control group received either tumor implantation or E. coli injection. MSCs significantly migrated towards tumor when compared to control mice without tumor or inflammatory process. However, mASCs injected in 4T1 bearing mice with E. coli only migrated towards the bacterial inflammatory focus. Our results substantiate the notation the MSCs response predominantly to the inflammatory milieu created by bacteria or tumor rather than specifically to the tumor. Thus, it is suggested that the migration of MSCs in immunodeficient mice depends on cancer secreted cytokines due to the lack of the inflammatory response by the immune system. Therefore, in vivo studies investigating the role of MSCs in tumor angiogenesis have shown controversy results and should be interpreted with caution in terms of tumor secreted cytokine dependent stem cell migration. Show more

Keywords: Mesenchymal stem cells, tumor angiogenesis, breast cancer, migration, immunsystem

DOI: 10.3233/CH-2011-1502

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 519-526, 2011

Authors: Stock, K.F. | Klein, B.S. | Cong, M.T. Vo | Regenbogen, C. | Kemmner, S. | Büttner, M. | Wagenpfeil, S. | Matevossian, E. | Renders, L. | Heemann, U. | Küchle, C.

Article Type: Research Article

Abstract: Background and purpose: Beyond the medical history, the clinical exam and lab findings, non-invasive ultrasound parameters such as kidney size and Doppler values (e.g. the resistive index) are important tools assisting clinical decision making in the monitoring of renal allografts. The gold standard for the diagnosis of renal allograft dysfunction remains the renal biopsy; while an invasive procedure, the justifiable necessity for this derives from its definitive nature a requirement beyond the synopses of all non-invasive tools. “Acoustic Radiation Force Impulse Imaging”(ARFI)-quantification is a novel ultrasound-based technology measuring tissue elasticity properties. So far experience related to this new method has …not been reported in renal transplant follow-up. The purpose of this study was to evaluate changes in ARFI-measurements between clinically stable renal allografts and biopsy-proven transplant dysfunction. Methods: We employed “Virtual Touch™ tissue quantification” (Siemens Acuson, S2000) for the quantitative measurement of tissue stiffness in the cortex of transplant kidneys. We performed initial baseline and later disease-evaluative ultrasound examinations in 8 renal transplant patients in a prospective study design. Patients were first examined during stable allograft function with a routine post-transplant renal ultrasound protocol. A second follow-up examination was carried out on subsequent presentation with transplant dysfunction prior to allograft biopsy and histological evaluation. All patiens were examined using ARFI-quantification (15 measurements/kidney). Resistive indices (RI) were calculated using pulsed-wave Doppler ultrasound, and transplant kidney size was measured on B-mode ultrasound images. All biopsies were evaluated histologically by a reference nephropathologist unaware of the results of the ultrasound studies. Histopathological diagnoses were based on biopsy results, taking clinical and laboratory findings into account. Finally we calculated the relative changes in ARFI-quantification, resistive indices and the absolute change of kidney size on a percentage basis at these defined assessment times and compared the results with the final pathologic diagnosis. Results: Histological results enumerated five cases of acute T-cell-mediated rejection, one case of calcineurin inhibitor toxicity and two cases of acute tubular necrosis. Calcineurin inhibitor toxicity and acute tubular necrosis were subsumed as “other pathologies”. Mean ARFI-values showed an average increase of more than 15% percent in transplants with histologically proven acute rejection whereas no increase was seen in transplants with other pathologies. Mean RI-values showed no increase either in the diagnostic group of acute rejection, nor in the group with other pathologies. Kidney size showed a mean absolute increase of 0.5 centimetres in allografts with acute rejection, whereas a mean decrease of 0.17 centimetres was seen in the group with other pathologies. Conclusion: As shown before in other studies, RI values andkidney size are of doubtful utility in the evaluation of kidneyallograft dysfunction. ARFI-based elasticity measurement showspromise as a complementary non-invasive parameter in follow-ondiagnosis of renal allograft rejection. Show more

Keywords: Ultrasonography, elasticity imaging techniques, kidney, kidney transplantation, Doppler ultrasonography, ARFI, graft rejection

DOI: 10.3233/CH-2011-1503

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 527-535, 2011

Authors: Helck, A. | D'Anastasi, M. | Notohamiprodjo, M. | Thieme, S. | Reiser, M. | Clevert, D.A.

Article Type: Research Article

Abstract: Purpose: To evaluate the potential benefit of three-dimensional ultrasound in the assessment of renal lesions. Materials and methods: 21 patients with unclear renal findings were prospectively included in the study. Every patient was examined using two-dimensional (2D) ultrasound (US), X-plane technique (simultaneous display of main image and second image at a plane at right angles to the first), and real time three-dimensional (3D) US. The imaging model used were standard gray scale-, duplex- and contrast-enhanced ultrasound (CEUS). All acquisitions were compared to each other with regard to image quality and identifiability of renal lesions. Additionally, when using the X-plane technique …the quality of the first and the second image were analysed separately. The assessment was done using a subjective 6 point scale (1 = best). Results: All acquisitions were successfully performed and no patient had to be excluded. Image quality of real time 3D-US (score: 2.4 ± 0.73) was slightly inferior to 2D-US and X-plane technique (main image) with a score of 2.2 ± 0.43 and 2.2 ± 0.5, respectively. The image quality of second image in the X-plane mode –due to a lower spatial resolution- was lower with a score of 3.2 ± 0.5. Real time 3D-US and X-plane technique allowed for better identifiability (score: 1.4 ± 0.59 and 1.9 ± 0.53) of renal lesions compared to 2D-US (score: 2.5 ± 0.6). The most marked difference was observed between the simultaneous use of real time 3D-US and X-plane technique versus 2D-US in case of renal cell carcinoma, especially with regard to extra-capsular tumor extension (score: 1.6 ± 0.52, 1.8 ± 0.71, and 3.0 ± 0.52, respectively). Conclusion: Assessment of renal lesions using real time 3D-US is feasible and improves the identifiability of renal lesions. Show more

Keywords: Renal lesions, real-time 3D, three-dimensional ultrasound, X-plane, image quality

DOI: 10.3233/CH-2011-1504

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 537-550, 2011

Article Type: Correction

Abstract: Erratum to [Clinical Hemorheology and Microcirculation 48 (1–3) (2011), 29–40] DOI 10.3233/CH-2011-1406

DOI: 10.3233/CH-2011-1511

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 551-551, 2011

Article Type: Other

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 553-560, 2011