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

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