Clinical Hemorheology and Microcirculation - Volume 61, issue 3

Authors: Vayá, Amparo | Alis, Rafael | Suescún, Marta | Rivera, Leonor | Murado, Julian | Romagnoli, Marco | Solá, Eva | Hernandez-Mijares, Antonio

Article Type: Research Article

Abstract: Increased red blood distribution width (RDW) in anemia is related to disturbances in the cellular surface/volume ratio, usually accompanied by morphological alterations, while it has been shown in inflammatory diseases that the activity of pro-inflammatory cytokines disturbing erythropoiesis increases RDW. Recently it has been reported that higher RDW is related with decreased erythrocyte deformability, and that it could be related with the association of RDW and increased risk of cardiovascular diseases. In order to analyze the influence of morphological alterations and proinflammatory status on the relationship between RDW and erythrocyte deformability, we analyzed erythrocyte deformability along with RDW and other …hematological and biochemical parameters in 36 α -thalassemia, 20 β-thalassemia, 20 δ β-thalassemia trait carriers, 61 metabolic syndrome patients and 76 morbidly obese patients. RDW correlated inversely with erythrocyte deformability in minor β-thalassemia (r  =−0.530, p  <  0.05), and directly in both metabolic syndrome and morbidly obese patients (ρ = 0.270, p  <  0.05 and ρ = 0.258, p  <  0.05, respectively). Minor β-thalassemia is often accompanied by more marked cell-shaped perturbations than other thalassemia traits. This could be the reason for this negative association only in this setting. Higher anisocytosis seems to be associated with greater morphologic alterations (shape/volume), which reduce erythrocyte deformability. The proinflammatory profile in metabolic patients can be related to the positive association of RDW with erythrocyte deformability found in these patients. However, further research is needed to explain the mechanisms underlying this association. Show more

Keywords: Erythrocyte deformability, red blood cell distribution width, metabolic diseases, thalassaemia trait

DOI: 10.3233/CH-141859

Citation: Clinical Hemorheology and Microcirculation, vol. 61, no. 3, pp. 407-415, 2015

Authors: Ranucci, Marco | Ranucci, Matteo | Laddomada, Tommaso | Baryshnikova, Ekaterina | Nano, Giovanni | Trimarchi, Santi

Article Type: Research Article

Abstract: BACKGROUND: Platelet reactivity changes with shear stress, which in turn depends on whole blood and plasma viscosity (PV). Platelets interact with fibrinogen during thrombus formation, and fibrinogen is a determinant of PV. The respective role of PV and fibrinogen on platelet function is still unclear. METHODS: 30 patients undergoing vascular surgery were admitted to this study. In each patient we measured PV using a cone-on-plate viscosimeter, functional fibrinogen using thromboelastometry, and platelet reactivity to thrombin receptor activating peptide (TRAP) stimulation using multi-electrode aggregometry. Routine coagulation parameter were measured. RESULTS: At the univariate analysis, platelet reactivity was …positively associated with mean platelet volume (R2  = 0.15, P  = 0.033) and PV (R2  = 0.35, P  = 0.0006), and negatively associated with serum bilirubin (R2  = 0.20, P  = 0.013) and international normalized ratio (INR) (R2  = 0.19, P  = 0.017). At the multivariable analysis, only PV (P  = 0.001) and INR (P  = 0.019) remained independent predictors of platelet reactivity. CONCLUSION: PV is directly and independently associated with platelet reactivity, whereas functional fibrinogen is not. Aspirin treatment is inadequate to correct thrombin-induced platelet aggregation. In presence of hyperviscosity, patients at high cardiovascular risk, may benefit from more aggressive anti-platelet treatments. Show more

Keywords: Plasma viscosity, fibrinogen, platelet reactivity, thrombin

DOI: 10.3233/CH-141866

Citation: Clinical Hemorheology and Microcirculation, vol. 61, no. 3, pp. 417-427, 2015

Authors: Koutsiaris, Aristotle G.

Article Type: Research Article

Abstract: The axial blood velocity (Vax) association with microvessel diameter (D) was studied at 104 different postcapillary venules (4 μm <  D <  24 μm) and 30 different precapillary arterioles (6 μm≤D≤12 μm) in the human conjunctiva of normal healthy humans. Venular diameter sizes were classified as “very small” (Group 1, 4.4 μm≤D <  8.9 μm), “small” (Group 2, 8.9 μm≤D <  13.8 μm), “medium” (Group 3, 13.8 μm≤D <  19.1 μm) and “large” (Group 4, 19.1 μm≤D≤23.5). The Spearman’s correlation coefficient (r s ) in all 4 venular groups was less than 0.36 and not statistically significant (n  = 26, p ≥0.08). Similar correlation results …were observed for the arteriolar group (r s ) ≈ 0) for the peak systolic, the average and the end systolic axial velocities. Vax was significantly (p  <  0.001) lower in Group 1 in comparison to that in Group 2 and significantly (p  <  0.01) lower in Group 2 in comparison to that in Group 3. However, Vax was not significantly lower in Group 3 in comparison to that in Group 4. Average Vax and standard deviation was 0.48 ± 0.13, 0.64 ± 0.16, 0.82 ± 0.25 and 0.88 ± 0.32 mm/s for Groups 1, 2, 3 and 4 respectively. The above results reinforce the importance of measuring D in microvascular hemodynamics. Higher diameters suggest higher axial velocities but Vax does not change significantly within the limits of each of the aforementioned groups. Show more

Keywords: Human, eye, conjunctiva, venules, arterioles, axial velocity, diameter, correlation

DOI: 10.3233/CH-141888

Citation: Clinical Hemorheology and Microcirculation, vol. 61, no. 3, pp. 429-438, 2015

Authors: Klonizakis, M. | Manning, G. | Lingam, K. | Donnelly, R. | Yeung, J.M.C.

Article Type: Research Article

Abstract: AIMS: To evaluate endothelial-dependent and – independent cutaneous vasodilator responses in the feet of patients with peripheral arterial disease (PAD) with or without Type 2 diabetes. METHODS: Cutaneous microvascular responses in the dorsum of both lower limbs were measured in the supine position using Laser Doppler Fluximetry combined with iontophoretic administration of endothelial-dependent (acetylcholine, Ach) and -independent (sodium nitroprusside, SNP) vasodilators in diabetic (n  = 19) and non diabetic (n  = 17) patients with PAD (presenting as unilateral calf intermittent claudication (IC). RESULTS: In patients with diabetes and IC, endothelial-dependent vasodilation was significantly impaired in the symptomatic limb …[74 (57,105) vs 68 (24,81) PU, Z =−2.79, p  = 0.005] compared to the asymptomatic limb. Patients without diabetes showed no impairment of vasodilation. Resting ankle-brachial pressure index did not identify the presence of abnormalities in microvascular function. CONCLUSIONS: The combination of diabetes and PAD is associated with a reduction in endothelial-dependent cutaneous vasodilation in the feet without an associated reduction in endothelial independent vasodilation. Show more

Keywords: Type 2 diabetes, peripheral arterial disease, microvascular function, endothelial dysfunction

DOI: 10.3233/CH-141907

Citation: Clinical Hemorheology and Microcirculation, vol. 61, no. 3, pp. 439-444, 2015

Authors: Namgung, Bumseok | Sakai, Hiromi | Kim, Sangho

Article Type: Research Article

Abstract: Human red blood cells (RBCs) were perfused in a circular micro-tube (inner diameter of 25 μm) to examine the dynamic changes of cell-free marginal region at both physiological (normal) and pathophysiological (hyper) levels of RBC aggregation. The cell-free area (CFA) was measured to provide additional information on the cell-free layer (CFL) width changes in space and time domains. A prominent enhancement in the mean CFL width was found in hyper-aggregating conditions as compared to that in non-aggregating conditions (P  <  0.001). The frequent contacts between RBC and the tube wall were observed and the contact frequency was greatly decreased when …the aggregation level was increased from none to normal (P  <  0.05) and to hyper (P  <  0.001) levels. In addition, the enhanced aggregation from none to hyper levels significantly enlarged the CFA (P  <  0.01). We concluded that the RBC aggregation at pathophysiological levels could promote not only the CFL width (one-dimensional parameter) but also the spatiotemporal variation of CFA (two-dimensional parameter). Show more

Keywords: Plasma layer, red blood cell, hemodynamic, microcirculation

DOI: 10.3233/CH-141909

Citation: Clinical Hemorheology and Microcirculation, vol. 61, no. 3, pp. 445-457, 2015

Authors: Bajuk, Nataša Bedernjak | Zaletel, Katja | Gaberšček, Simona | Lenasi, Helena

Article Type: Research Article

Abstract: BACKGROUND: The impact of hyperthyroidism induced by Graves’ disease (GD) on skin microcirculation has not been established. We aimed to assess vascular reactivity in hyperthyroid GD patients before and during treatment. METHODS: Laser Doppler flux (LDF) was measured in 31 newly diagnosed hyperthyroid GD patients with an increased TSH receptor stimulating antibody (TSAb) levels before the methimazole treatment; and again 5.8 ± 0.8 months later when euthyroidism had been established; and in 30 healthy age- and gender-matched controls. Postocclusive reactive hyperaemia (PRH) was assessed by a 3-min occlusion of the brachial artery. RESULTS: Baseline LDF on …the finger pulp and on the volar forearm were significantly higher in untreated GD patients compared to treated GD patients and controls (p  <  0.05 for both). On the finger pulp, the time to maximal LDF during PRH was significantly shorter in untreated GD patients compared to controls (p  <  0.05). On the forearm, the duration of PRH was significantly longer in untreated GD patients compared to controls (p  <  0.05). Positive correlations of triiodothyronine and TSAb with some indices of PRH were established in treated GD patients. CONCLUSIONS: Hyperthyroidism induced by GD reversibly affects skin microcirculation, presumably by increasing the vasodilator capacity. Potential involvement of TSAb might be implicated. Show more

Keywords: Graves’ disease, hyperthyroidism, skin microcirculation, laser Doppler fluxmetry, postocclusive reactive hyperaemia

DOI: 10.3233/CH-141911

Citation: Clinical Hemorheology and Microcirculation, vol. 61, no. 3, pp. 459-470, 2015

Authors: Vayá, Amparo | Sarnago, Ana | Ricart, José M. | López, Verónica | Martínez-Triguero, M.L. | Laiz, Begoña

Article Type: Research Article

Abstract: It is not well-established whether patients with androgenetic alopecia (AGA) show a higher cardiovascular risk and higher prevalence of metabolic syndrome (MS). Therefore, we aimed to analyze the cardiovascular risk and the prevalence of MS by means of a case-control study. We determined lipidic, inflammatory, hormonal and insulin resistance parameters with conventional laboratory methods in 50 male early-onset AGA patients and 50 controls. AGA patients did not show statistical differences for insulin resistance (glucose, insulin, C peptide, HOMA), lipids (total-cholesterol, HDL-cholesterol, tryglicerides) or hormonal parameters (testosterone, free androgen index, sex hormone-binding globulin) P  >  0.05, respectively. No differences between groups …were observed in prevalence of MS or its components (P  >  0.05). AGA patients showed higher levels of fibrinogen, C-reactive protein (CRP) and lipoprotein(a) (Lp(a)) (P  = 0.016, P  = 0.019 and P  = 0.032, respectively). In the unadjusted logistic regression analyses, PCR >4 mg/L, fibrinogen >395 mg/dL and Lp(a) >59 mg/dL increased the risk of AGA, but in the adjusted logistic regression analyses, only PCR >4 mg/L and Lp(a) >59 mg/dL independently increased this risk (OR = 5.83, 95% CI 1.33–25.59 P  = 0.020; OR = 3.94 CI 95% 1.08–14.43 P  = 0.038). The present study indicates that AGA patients do not show differences in either insulin resistance or prevalence of MS. However, AGA patients show a higher cardiovascular risk characterised by an increase in inflammatory parameters and Lp(a) levels. Show more

Keywords: Androgenetic alopecia, inflammatory parameters, cardiovascular risk

DOI: 10.3233/CH-141913

Citation: Clinical Hemorheology and Microcirculation, vol. 61, no. 3, pp. 471-477, 2015

Authors: Nemeth, Norbert | Berhes, Mariann | Kiss, Ferenc | Hajdu, Endre | Deak, Adam | Molnar, Abel | Szabo, Judit | Fulesdi, Bela

Article Type: Research Article

Abstract: The pathophysiology of hemorheological and microcirculatory disturbances in septic process -mostly during the early hours- still not clarified in all the details, yet. In anesthetized pigs living E. coli (ATCC 25922 strain) was administered intravenously with an increasing concentration and the animals were observed for 8 hours. Before the intervention and in every 2 hours arterial (cannulated femoral artery) and venous (cannulated external jugular vein) blood samples were collected for hemorheological laboratory tests: blood and plasma viscosity, ESR, leukocyte anti-sedimentation rate, erythrocyte deformability (together with osmoscan parameters) and erythrocyte aggregation (using light-transmission and laser back-scattering methods) Control animals were …stable over the 8-hour anesthesia, while septic animals died by the 6th hours in a fulminant sepsis. Over the experimental period, the tendency of impairment in erythrocyte deformability (together with osmotic gradient ektacytometry parameters) and the controversial decreasing of erythrocyte aggregation values (declining all aggregation index values, elongating t1/2 ) were well detected in this porcine model during the early hours (4– 6) of fulminant sepsis. The in vitro effect of these bacteria on erythrocytes’ micro-rheological parameter was similar: decreasing red blood cell deformability and lowering aggregation. Further studies are needed to clarify the early micro-rheological changes of bacteremia and the developing sepsis. Show more

Keywords: Red blood cell deformability, red blood cell aggregation, E. coli, sepsis, animal model

DOI: 10.3233/CH-141914

Citation: Clinical Hemorheology and Microcirculation, vol. 61, no. 3, pp. 479-496, 2015

Authors: Lee, Seahyoung | Yu, Long-Hao | Lim, La-Ri | Lim, Hee-Jung | Si, Jung-Eun | Ko, Young-Guk | Hwang, Ki-Chul

Article Type: Research Article

Abstract: The major cause of diabetes-related mortality is the complications involving aberrant angiogenesis. To understand the underlying mechanisms of such altered-angiogenesis in diabetes, examining the interaction between endothelial cells (ECs) and neighboring smooth muscle cells (VSMCs) rather than mainly focusing on EC might provide us useful information. Thus, in the present study, we examined the effect of high glucose on the expression of Jag1, one of the key trans-activating ligands of Notch receptors known to be involved in EC-SMC interaction, as well as angiogenic process, in vascular smooth muscle cells (VSMCs) to elucidate possible role of EC-VSMC interaction in diabetes-related angiopathy. …Our data indicate that high glucose condition decreases the expression of Jag1 in VSMCs possibly by increasing Jag1 -targeting micro RNAs (miRNAs) such as miR-21, and exogenous Jag1-simulating peptides increase proliferation and migration of ECs under high glucose condition in vitro . Ex vivo study using aortic rings from normal and streptozotocin (STZ)-treated diabetic mouse demonstrated that exogenous Jag1-simulating peptides increases EC sprouting of aortic rings from diabetic mouse under high glucose condition. Our data suggest that EC-VSMC interaction is altered under high glucose condition and restoring EC-VSMC interaction can be a feasible therapeutic target for treating diabetes-related angiopathy. Show more

Keywords: High glucose, vascular smooth muscle cell, Jag-1, miR-21, Angiogenesis, aortic ring assay

DOI: 10.3233/CH-141915

Citation: Clinical Hemorheology and Microcirculation, vol. 61, no. 3, pp. 497-511, 2015

Authors: Karabacak, Mustafa | Yiğit, Mehmet | Turkdogan, Kenan Ahmet | Yiğit, Eda | Selek, Sehabettin

Article Type: Research Article

Abstract: BACKGROUND: Platelet activation might play a significant role in the pathophysiology of cardiovascular and cerebrovascular events in hypertension (HT). Signal peptide-CUB-EGF domain-containing protein1 (SCUBE1), an indicator of platelet activation, is increased in HT. The aim of this study was to investigate the SCUBE1 in patients with hypertensive crises. METHODS: This study included 33 hypertensive urgency (HU) and 39 hypertensive emergency (HI) patients admitted to our emergency department with a diagnosis of hypertensive crisis. Platelet activation was evaluated with biochemical markers such as SCUBE1, soluble CD40L (sCD40L), mean platelet volume, and platelet count. RESULTS: The SCUBE1 values …of the HE patients were significantly higher than other groups (1.09 ± 0.49, 0.71 ± 0.23 and 0.37 ± 0.02 ng/dl, respectively; p  <  0.01). The sCD40L values were higher in the hypertensive crises compared with the control group (4.16 ± 1.82, 3.41 ± 1.76 and 1.76 ± 0.68 ng/ml, respectively; p  <  0.01). More importantly, SCUBE1 had high sensitivity and specificity in the detection of target organ damage. CONCLUSION: In present study showed that SCUBE1 was significantly higher in HE patients. In addition, sCD40L level, presence of diabetes, and systolic blood pressure were independently associated with increased SCUBE1. According to our results, SCUBE1 might be a diagnostic biomarker in hypertensive crisis patients. Show more

Keywords: Hypertensive crises, signal peptide-CUB-EGF domain-containing protein1, target organ damage, soluble CD40 ligand, mean platelet volume

DOI: 10.3233/CH-141917

Citation: Clinical Hemorheology and Microcirculation, vol. 61, no. 3, pp. 513-522, 2015

Authors: Cherkouk, Charaf | Rebohle, Lars | Lenk, Jens | Keller, Adrian | Ou, Xin | Laube, Markus | Neuber, Christin | Haase-Kohn, Cathleen | Skorupa, Wolfgang | Pietzsch, Jens

Article Type: Research Article

Abstract: Gold surfaces functionalized with nickel-nitrilotriacetic acid (Ni2+ -NTA) as self-assembled monolayers (SAM) to immobilize histidine (His)-tagged biomolecules are broadly reported in the literature. However, the increasing demand of using microfluidic systems and biosensors takes more and more advantage on silicon technology which provides dedicated glass surfaces and substantially allows cost and resource savings. Here we present a novel method for the controlled oriented immobilization of His-tagged proteins on glass surfaces functionalized with a Ni2+ -NTA layer. Exemplarily, the protein pattern morphology after immobilization on the Ni2+ -NTA layer of His6 -tagged soluble receptor for advanced glycation endproducts (sRAGE) was investigated …and compared to non-oriented immobilization of sRAGE on amino SAM by using scanning electron microscopy (SEM). Moreover, we demonstrated interaction of immobilized sRAGE with three structurally different ligands, S100A12, S100A4, and glycated low density lipoproteins (glycLDL), by means of peak-force tapping atomic force microscopy (PF-AFM). We showed a clear discrimination of different protein-ligand orientations by differential height measurements. Show more

Keywords: His-tagged proteins, glycated low density lipoproteins, microfluidic systems and biosensors, S100 proteins, self-assembled monolayers, soluble receptor for advanced glycation endproducts

DOI: 10.3233/CH-151950

Citation: Clinical Hemorheology and Microcirculation, vol. 61, no. 3, pp. 523-539, 2015

Authors: Pabisiak, A. | Bromboszcz, J. | Kmiec, S. | Dendura, M. | Dabrowski, Z. | Smolenski, O.

Article Type: Research Article

Abstract: INTRODUCTION: The aim of cardiovascular disease treatment is to reduce the risk of thrombogenesis and improve tissue perfusion, depending inter alia on the rheological properties of the blood. The reduction in blood viscosity and erythrocyte aggregation, as well as increase of erythrocyte deformability was observed under the influence of physical training. AIM: To compare the blood count and rheological properties of blood samples before and after outpatient cardiac rehabilitation programme. MATERIAL AND METHODS: 35 men (average age: 57.2 ± 5.42), who after suffering myocardial infarction treated with percutaneous coronary intervention (PCI), took part in 24 physical …training sessions of moderate intensity (40–60% of heart rate reserve). The standard ergometer submaximal (up to 85% of predicted HRmax) exercise test and echocardiography was performed before and after training. Blood count, fibrinogen concentration as well as aggregation and elongation properties of erythrocytes were analyzed too. RESULTS: Patients significantly increased exercise capacity (p  <  0.00001) and ejection fraction (p  <  0.00001) after completion of the training cycle. There was noted a reduction in aggregation index AI (p  <  0.01), an increase in the number of erythrocytes RBC (p  <  0.05), while reducing their volume MCV (p  <  0.05) and a decrease in hemoglobin content MCH (p  <  0.05). The number of leukocytes WBC (p  <  0.01) was decreased too. CONCLUSIONS: Beneficial changes in blood rheology and blood count have been found in patients after myocardial infarction who took part in the physical training sessions of moderate intensity. Show more

Keywords: Myocardial infarction, rehabilitation, physical training, blood count, blood rheology

DOI: 10.3233/CH-151954

Citation: Clinical Hemorheology and Microcirculation, vol. 61, no. 3, pp. 541-547, 2015

Authors: Jung, Christian | Drummer, Karl | Oelzner, Peter | Figulla, Hans R. | Boettcher, Joachim | Franz, Marcus | Betge, Stefan | Foerster, Martin | Wolf, Gunter | Pfeil, Alexander

Article Type: Research Article

Abstract: Systemic sclerosis (SSc) is a systemic, autoimmune connective tissue disease characterized by vasculopathy and microvascular changes. Fluorescence Optical Imaging (FOI) is a technique used to assess inflammation in patients with arthritis; in this study FOI is used to quantify inflammation in the hand. Endothelial Microparticle (EMP) can reflect damage or activation of the endothelium but also actively modulate processes of inflammation, coagulation and vascular function. The aim of the present study was to quantify EMP and FOI, to determine an association between these microparticles and inflammation and to endothelial function. METHODS: EMP were quantified in plasma samples of 25 …patients (24 female, 1 male, age: 41 ± 9 years) with SSc using flow cytometry. EMP was defined as CD31+/CD42− MP, and CD62+ MP. Perivascular inflammation was assessed using fluorescence optical imaging (FOI) of the hand. Macrovascular endothelial function was non-invasively estimated using the Endopat system. RESULTS: Plasma levels of CD31+/CD42− EMP and CD62+ EMP were lower in patients with SSc compared to controls (both p  <  0.05). An impaired endothelial function with an increased hyperemia index was observed. A strong association could be demonstrated between CD62+ EMP and perivascular soft tissue inflammation as assessed by the FOI global score (Spearman, p  = 0.002, r  = 0.61). CONCLUSIONS: EMP indicate molecular vascular damage in SSc; in this study a strong association between EMP and perivascular inflammation as quantified by FOI is demonstrated. Consequently EMP, using FOI, may be a potential marker benefitting the diagnosis and therapy monitoring of patients with SSc with associated Raynaud‘s phenomenon. Show more

Keywords: Systemic sclerosis, endothelial microparticles, fluorescence optical imaging, microcirculation

DOI: 10.3233/CH-151956

Citation: Clinical Hemorheology and Microcirculation, vol. 61, no. 3, pp. 549-557, 2015