Clinical Hemorheology and Microcirculation - Volume 54, issue 3

Authors: Paternotte, Estelle | Kerdjoudj, Halima | Kokten, Tunay | Stoltz, Jean-Francois | Kearney-Schwartz, Anna | Voegel, Jean-Claude | Menu, Patrick

Article Type: Research Article

Abstract: The major challenge of vascular tissue engineering is to develop a small calibre vascular graft with a high patency rate. In native vessels, the thrombosis is prevented by the endothelium located at the luminal site of the vessel. The aim of this study was to develop a resistant endothelial lining on the inner surface of vascular graft using a polyelectrolyte multilayers (PEM) film. Umbilical arteries were de-endothelialized, coated with 3.5 bilayers of poly(styrene sulfonate) (PSS)/poly(allylamine hydrochloride) (PAH) and then cellularized with endothelial cells. The grafts were cultured for a week in static condition and preconditioned by exposure to a shear …stress of at 1 Pa for three hours before implantation on the rabbit carotid site. Histological and confocal microscopy in vitro investigations showed that PEMs films improve cell adhesion and retention on the luminal surface after shear stress preconditioning. In vivo Doppler data showed that graft preconditioning is a crucial factor for graft patency. Indeed, preconditioned grafts remained over the whole experimental period, whereas unpreconditioned grafts were obstructed after only one week of implantation. These results open the route toward the development of a new generation of vascular substitutes having a long term patency. Show more

Keywords: Vascular substitutes, polyelectrolyte multilayer films, shear stress, bypass, endothelial cells

DOI: 10.3233/CH-131728

Citation: Clinical Hemorheology and Microcirculation, vol. 54, no. 3, pp. 223-234, 2013

Authors: Braune, Steffen | von Ruesten-Lange, Maik | Mrowietz, Christof | Lützow, Karola | Roch, Toralf | Neffe, Axel T. | Lendlein, Andreas | Jung, Friedrich

Article Type: Research Article

Abstract: Linear, side-chain methylated oligoglycerols (OGMe) were recently reported as potential surface passivating molecules for improving the protein resistance of cardiovascular application relevant poly(ether imide) (PEI) membranes. A previously reported in vitro screening under static test conditions allowed an end-point evaluation of the adhesion and activation of adherent thrombocytes performed on the material surfaces and revealed similar levels of thrombogenicity on PEI membranes, functionalized with OGMe and oligo(ethylene glycol) (OEG) of similar molecular weight (Mn = 1,300 g·mol−1 - 1,800 g·mol−1 ). In the present study, we investigated the hemocompatibility of these materials in a dynamic closed loop system, …in order to study time-dependent thrombocyte material interactions also of the circulating thrombocytes by mimicking in vivo relevant flow conditions in a dynamic test system with multiple material contacts. Activation and aggregation of circulating thrombocytes as well as complement activation and plasmatic coagulation were evaluated after 40 circulations of thrombocyte rich plasma in the closed loop system. The results of the dynamic tests revealed no differences between the OGMe and OEG functionalized PEI membranes. Furthermore, no differences were observed between the latter and a PEI membrane treated under the conditions of functionalization at pH 11 (PEI-pH11) without an oligoether being present. Blood plasma protein adsorption, as well as activation, and adherence of circulating thrombocytes occurred in a comparable, but minor manner on all investigated PEI membranes. From this we conclude that the OGMe and OEG surface functionalization did not lead to an improvement of the already good hemocompatibility of the PEI-pH11 membrane. Show more

Keywords: Oligoglycerol, protein resistance, hemocompatibility, surface functionalization, membranes, biomaterial

DOI: 10.3233/CH-131729

Citation: Clinical Hemorheology and Microcirculation, vol. 54, no. 3, pp. 235-248, 2013

Authors: Weiss, Andreas | Brose, Stefan | Ploetze, Katrin | Matschke, Klaus

Article Type: Research Article

Abstract: BACKGROUND: Patients who require oral anticoagulation (OAC) after cardiac surgery due to an increased risk for thromboembolic events should receive bridging therapy with heparin until the INR is in a therapeutic range. For this purpose, unfractionated heparin (UFH) or low molecular weight heparin (LMWH) can be used. Recently published studies have demonstrated the safety and efficiency of therapeutic dose LMWH as bridging anticoagulant in cardiac surgery. The present study compares a full-therapeutic dose regimen with a half-therapeutic dose regimen of LMWH looking for safety and efficiency. PATIENTS AND METHODS: This study represents a retrospective, single-center cohort study. In a period …of 19 months all patients in whom a postoperative bridging therapy after cardiac surgery was necessary (atrial fibrillation, mechanical heart valve replacement, tricuspid valve repair, intracardiac patch implantation, excision of intracardiac tumors) were selected. In the first part of the study, patients received full-dose (FD = 1 mg/kg bodyweight twice daily) LMWH (Enoxaparin). Analogously, patients in the second part of the study were treated with half-dose (HD = 0.5 mg/kg bodyweight twice daily) LMWH. In case of renal insufficiency (GFR <30 ml/min) the dose was adjusted to one daily application. The duration of follow-up was the patients' entire stay in hospital. Main outcome parameters were bleeding, thromboembolic events, and death. The first dose of LMWH was given on the morning of the first postoperative day, considered that the bleeding risk was acceptable. OAC (Phenprocoumon) was started on the evening of the first postoperative day. RESULTS: Altogether 402 out of 3133 patients met the inclusion criteria (201 patients in each group). Despite a reduced renal function in the HD-group (p = 0.002) both groups were well matched. Mortality was significantly higher in the HD-group than in the FD-group (5.5% vs. 0.5%, p = 0.003) but not related to the anticoagulation regimen. We observed more bleeding events in the FD-group (11 vs. 5, p = 0.126) but vice versa more thromboembolic events in the HD-group (9 vs. 5, p = 0.277). In the HD-group postoperative dialysis was required more often (29 vs. 12, p = 0.011) and there was a higher incidence of patients who were psychic disorientated (42 vs. 26, p = 0.033). The hospital stay was longer in the FD-group (FD: 15.1 ± 9.3 days, HD 12.5 ± 8.1 days, p = 0.003). CONCLUSION: This study shows that a bridging therapy with LMWH is feasible and safe no matter which dose-regimen is used. The differences observed seem not to be related to the anticoagulation. The decision of using a full-dose or half-dose LMWH bridging regimen should be determined by the individual risk of the patient and the general bleeding risk of the procedure. Show more

Keywords: Low molecular weight heparin, enoxaparin, cardiac surgery, bridging therapy, oral anticoagulation

DOI: 10.3233/CH-131731

Citation: Clinical Hemorheology and Microcirculation, vol. 54, no. 3, pp. 249-258, 2013

Authors: Wei, Xi | Li, Ying | Zhang, Sheng | Li, Xubin | Wang, Hailing | Yong, Xu | Wang, Xiaoqing | Li, Xing | Gao, Ming

Article Type: Research Article

Abstract: OBJECTIVE: To evaluate the dynamic microvascularization of focal salivary gland lesions by contrast-enhanced ultrasound (CEUS) and Color Doppler sonography. MATERIALS AND METHODS: One hundred and sixty-eight patients with 183 major salivary gland lesions (mean age, 56 years; age range, 12–83 years) underwent gray-scale ultrasonography (US), Color Doppler (CD) and CEUS. The CD and CEUS patterns were classified into three types (scores 0–3). Combined score grades were calculated based on the CD and CEUS pattern scores. The time-intensity curve (TIC) parameters of CEUS were then analyzed. Sensitivity, specificity, negative predictive value and positive predictive value of combined score grades were also …calculated. RESULTS: Among all the lesions, there were 161 in parotid gland, 22 in submandibular gland and 157 lesions were benign and 26 were malignant. For score grades (combined CEUS patterns with CD types), scores 1-2 were graded as benign; scores 3-4 were graded as indetermination-suspicious benign or malignant and scores 5-6 were graded as malignant.score 5-6 and score 1-2 indicated 24 (92.3%) and 135 (85.9%) malignant and benign lesions confirmed pathologically, respectively. The sensitivity and negative predicted value of combined score grades for malignant lesions were 92.3% and 98.5%, respectively. In addition, TIC analysis indicates that PI and AUC in malignant lesions were higher than those in benign lesions (p = 0.04 and 0.02, respectively). CONCLUSION: The combined score grade could be a useful method to assess the macro-and micro-vascularization and to differentiated diagnose benign and malignant lesions in major salivary glands. Show more

Keywords: Salivary gland lesions, microvascularity, CEUS, Color Doppler, combined score grade

DOI: 10.3233/CH-131732

Citation: Clinical Hemorheology and Microcirculation, vol. 54, no. 3, pp. 259-271, 2013

Authors: Franke, R.P. | Scharnweber, T. | Fuhrmann, R. | Mrowietz, C. | Jung, F.

Article Type: Research Article

Abstract: Red blood cells demonstrate a unique ability for repeated large deformation. Under the influence of a variety of agents, shapes other than the discocyte – e.g. stomatocytes or echinocytes - can be observed. Some radiographic agents induce shape changes from discocytic to echinocytic cells. Especially the echinocyte formation is associated with a rigidification of the cells bearing the risk of a hindered capillary passage of the echinocytes. The mechanisms leading to the formation of echinocytes are not well understood assuming that the membrane cytoskeleton is a key player. That is why this examination was focused on the participation of components …of the membrane cytoskeleton in the formation of echinocytes and the protrusions accompanying the formation of echinocytes. Two radiographic contrast media approved for intra-arterial application were used to study echinocyte formation (Iodixanol320; Iopromide370). In the in vitro study serious changes in the membrane cytoskeleton were only found in those erythrocytes incubated in plasma supplemented with Iopromide370 (30%v/v). The shape of the spectrin net was completely altered; from the more homogeneous distribution - typical of cells in autologous plasma and also of cells in plasma supplemented with Iodixanol320 – to a distribution of spectrin concentrated in the membrane-near regions with the appearance of spectrin-actin co-localization. Co-localized spectrin with actin was also found around the membranous roots of protrusions which resemble exocytotic processes. In central parts of the cells there was a pronounced dissociation of spectrin and actin; green coloured condensed spectrin bundles originating from the cell membrane reached up to the root of the protrusions. Separate from this there were also fine long actin fibres passing through the whole cell. The incubation of erythrocytes in plasma supplemented with Iopromide370 induced rounded bubble-like protrusions from the cell membrane containing almost completely long bundles of actin fibres. The examination confirmed earlier studies showing that some radiographic contrast media are able to induce echinocyte formation. Furthermore, subcellular mechanisms were revealed explaining the different effects of Iodixanol in comparison to Iopromide. Show more

Keywords: Erythrocytes, Iodixanol, Iopromide, spectrin, actin

DOI: 10.3233/CH-131733

Citation: Clinical Hemorheology and Microcirculation, vol. 54, no. 3, pp. 273-285, 2013

Authors: Vayá, Amparo | Alis, Rafael | Romagnoli, Marco | Pérez, Rafael | Bautista, Daniel | Alonso, Ricardo | Laiz, Begoña

Article Type: Research Article

Abstract: It is not well-established whether the alterations that the hemorheological profile undergoes with aging are an effect of concomitant cardiovascular risk factors or are due to age itself. To clarify this issue, we investigated the effect of age on blood rheology in a population of 927 healthy subjects from eastern Spain aged between 16–85 years, divided into four age groups (<30, 30–44, 45–50, ≥60 years) with and without cardiovascular risk factors. We determined blood viscosity, corrected blood viscosity (BVc), plasma viscosity (PV), erythrocyte aggregation (EA), erythrocyte deformability (EEI60) and fibrinogen, along with glucose and plasma lipids. We found that corrected …blood viscosity (p = 0.007), plasma viscosity, erythrocyte aggregation, fibrinogen, glucose, and plasma lipids increased with age (p < 0.001). When subjects with cardiovascular risk factors were excluded, the effect of age on blood rheology persisted for all the cited parameters (p < 0.028). EEI60 increased with age (p = 0.033), and it was attributable to a concomitant increase in mean corpuscular volume (p < 0.001). In the Pearson's correlations, age was related to all the parameters analyzed (P < 0.019). The logistic regression analysis revealed that PV ≥1.30 mPa·s, BVc ≥4.90 mPa·s and EA1 ≥8.3 were associated with age ≥60 years (* p = 0.049, * p = 0.013, * p = 0.045, respectively). These results indicate that, although the presence of cardiovascular risk factors influences rheological properties, aging itself is associated with deterioration of rheological blood behavior, mostly related to inflammatory and lipidic changes. Show more

Keywords: hemorheology, cardiovascular risk factors, age

DOI: 10.3233/CH-131734

Citation: Clinical Hemorheology and Microcirculation, vol. 54, no. 3, pp. 287-296, 2013

Authors: Aufradet, Emeline | DeSouza, Geneviève | Bourgeaux, Vanessa | Bessaad, Amine | Campion, Yannick | Canet-Soulas, Emmanuelle | Pialoux, Vincent | Chirico, Erica N. | Chevrier, Anne-Marie | Godfrin, Yann | Martin, Cyril

Article Type: Research Article

Abstract: In sickle cell disease, the factors involved in vasoocclusive crisis (VOC) include the sickling of red blood cells (RBC), abnormal blood rheology, inflammation, vascular adhesion, oxidative stress, coagulation, and vascular tone modulation. The aim of this study was to further characterize the molecular response of some factors involved in VOC by inducing a hypoxia/reoxygenation stress in sickle SAD mice. Results show that a hypoxia/reoxygenation stress in SAD mice can induce: (i) a decrease in reticulocytes count, and mean corpuscular volume along with an increase in lactate dehydrogenase (p = 0.07) and sickled cell proportion; (ii) a significant increase in lung …VCAM-1, ICAM-1, IL-1β, ET-1, eNOS, and TF mRNA associated with an increase in VCAM-1 expression on lung endothelium; (iii) a rise in cardiac oxidative stress with increased lipid oxidation and decreased anti-oxidant enzyme activities, and (iv) an increase in plasma TNF-α and IL-6 and a decrease in plasma ET-1. In SAD mice, hypoxia/reoxygenation stress induces hemolysis that, together with oxidative stress, inflammation, vascular adhesion, and coagulation, may induce vascular occlusion and consequently RBC sickling. The present results give the kinetics of VOC molecular markers in SAD mice which may aid in testing the efficiency of new therapeutic processes against VOC. Show more

Keywords: Sickle cell anemia, transgenic mice, inflammation, oxidative stress, adhesion molecules

DOI: 10.3233/CH-131735

Citation: Clinical Hemorheology and Microcirculation, vol. 54, no. 3, pp. 297-312, 2013

Authors: Wiewiora, Maciej | Piecuch, Jerzy | Glűck, Marek | Slowinska-Lozynska, Ludmila | Sosada, Krystyn

Article Type: Research Article

Abstract: The aim of this study was to evaluate the effects of obesity on wall shear stress and its relationship to erythrocyte aggregation. We studied 35 morbidly obese patients who were qualified for bariatric surgery. The control group consisted of 20 non-obese people. Blood rheological measurements were performed using the Laser-assisted Optical Rotational Cell Analyzer (Mechatronics, the Netherlands) and a cone-plate viscometer (Brookfield DV-II). The venous flow dynamics were assessed using a duplex ultrasound. The shear rate was estimated from the measured blood flow velocity and the diameter of the femoral vein. Venous wall shear stress was calculated from the whole …blood viscosity and the shear rate. The shear rate (P < 0.005) and the venous wall shear stress (P < 0.05) were significantly lower in obese patients compared with the controls. The aggregation index (P < 0.001), syllectogram amplitude – AMP (P < 0.05) and Tslow (P < 0.001) were significantly higher in the obese patients; the aggregation half-time (P < 0.001) and Tfast (P < 0.001) were decreased compared with the control group. Multivariate regression analyses found waist circumference (β −0.31, P < 0.05), thigh circumference (β 0.33, P < 0.05) and Tslow (β −0.47, P < 0.005) to be variables that independently influenced the shear rate. Nevertheless, the AMP (β 0.34, P < 0.05) and Tslow (β −0.47, P < 0.01) were independent predictors that influenced the wall shear stress. This study indicates that there is a relationship between wall shear stress in the femoral vein and the rheological impairment of the RBC among obese patients, but further studies are necessary to confirm this suggestion. Show more

Keywords: obesity, venous wall shear stress, rheology

DOI: 10.3233/CH-131736

Citation: Clinical Hemorheology and Microcirculation, vol. 54, no. 3, pp. 313-323, 2013

Authors: Koster, M. | Amann-Vesti, B.R. | Husmann, M. | Jacomella, V. | Meier, T.O. | Jeanneret, C. | Hafner, J. | Thalhammer, C.

Article Type: Research Article

Abstract: OBJECTIVES: Venous pressure measurement using an intravenous catheter is the sole method for the diagnosis of venous hypertension in patients with chronic venous insufficiency. A noninvasive tool to quantify increased venous pressure is essential for studying venous pathophysiology. Aim of the study was to investigate the value of controlled compression ultrasound (CCU) for noninvasive assessment of venous pressure (VP) of the great saphenous vein (GSV) in healthy persons and patients with venous insufficiency to quantify venous hypertension. METHODS: An optimal visible part of the GSV directly above the ankle was marked on the skin and compressed under ultrasound control and …pressure needed for complete compression of the vein was recorded using a pressure manometer with a translucent silicone membrane. Complete insufficiency of the GSV (Hach IV) was documented by duplex ultrasound by an independent investigator before start of the study. VP measurement was performed while normal breathing, deep inspiration and expiration and during a standardized Valsalva maneuver. RESULTS: Twenty controls and 19 patients with complete insufficiency of the GSV were included. Valsalva maneuver induced a slight increase in VP in controls (20.1 ± 4.5 vs 25.1 ± 6.6 mbar) but a significant higher increase in patients from 26 to 37 mbar (IQR 18.5–28.0 vs 31.5–43.0; p < 0.001). CONCLUSION: Noninvasive venous pressure measurement of the great saphenous vein using CCU is feasible and documents an increased pressure during Valsalva maneuver in Hach IV patients compared to healthy controls. Show more

Keywords: Chronic venous insufficiency, venous hypertension, noninvasive pressure measurement, compression ultrasound

DOI: 10.3233/CH-131737

Citation: Clinical Hemorheology and Microcirculation, vol. 54, no. 3, pp. 325-332, 2013

Authors: Vayá, Amparo | Alis, Rafael | Hernández, Jose-Luis | Calvo, Javier | Micó, Luisa | Romagnoli, Marco | Ricart, Jose M.

Article Type: Research Article

Abstract: Red blood cell distribution width (RDW) is a routine parameter that reflects size variations in erythrocytes. High RDW has been associated with cardiovascular events and inflammatory diseases. However, no studies evaluating the association of RDW with systemic lupus erythematosus (SLE) have been published. We aimed to explore the association of RDW with inflammatory markers in SLE. As SLE is often associated with anaemia, we considered this factor in order to know whether RDW is related with inflammation, anaemia or both in SLE. The study included 105 SLE patients (7 men, 98 women; aged 15–73 years) and 105 controls (9 men, …96 women; aged 18–71 years). Patients were divided according to anaemia status (26 with, 79 without). Biochemical, hematological and inflammatory parameters (C-reactive protein (CRP), fibrinogen and erythrocyte aggregation (EA1)) were analyzed. SLE patients showed increased RDW, CRP and EA1 (p < 0.001), and decreased hemoglobin levels (p < 0.001) when compared with controls. RDW was higher in SLE patients with anaemia (a-SLE) as compared with those without anaemia (na-SLE) (p < 0.01) or controls (p < 0.001). CRP in a-SLE was higher than in controls (p < 0.01) but lower than in na-SLE (p < 0.05). In na-SLE RDW correlated directly with fibrinogen and CRP (p < 0.001), but not in a-SLE. Our results indicate that SLE patients show higher RDW irrespectively of anaemia status, and that RDW is influenced by both anaemia and inflammation, but the influence of anaemia is stronger. Show more

Keywords: Systemic lupus erythematosus, RDW, anaemia, inflammation

DOI: 10.3233/CH-131738

Citation: Clinical Hemorheology and Microcirculation, vol. 54, no. 3, pp. 333-339, 2013