Biorheology - Volume 41, issue 2

Authors: Dobbe, J.G.G. | Hardeman, M.R. | Streekstra, G.J. | Grimbergen, C.A.

Article Type: Research Article

Abstract: Background. The deformability of red blood cells (RBCs) is of great importance for the conservation of oxygen delivery in the microcirculation. Even a small fraction of rigid cells is considered to harm the exchange of respiratory gases. Techniques that measure RBC deformability often provide an indication of the mean deformability. It may not be possible, however, to assess whether this mean value is reduced by the presence of a small rigid cell fraction or by a slight overall reduction in RBC deformability. A technique that provides a deformability distribution would be of great value to study diseases that are marked …by subpopulations with a reduced deformability. Methods. This paper describes a rheoscope system that uses advanced image analysis techniques to quickly quantify the deformability of many individual cells in shear flow, in order to find the RBC‐deformability distribution. Since variations in the shear stress are responsible for variations in cell elongation, and hence introduce an additional spread in the cell deformability distribution, we first determined the spread caused by instrumental error. We then utilized the technique to investigate the relation between cell deformability and cell size of single blood samples of different species (human, pig, rat and rabbit). Results. The spread caused by instrumental error was small compared to the actual RBC‐deformability spread in blood samples. The deformability distribution of human and pig cells are alike although their cell sizes are different. Rat and rabbit cells show comparable deformability and size distributions. With this technique no correlation was found between cell deformability and cell size in animal RBCs. In the human sample a minor correlation was found between cell deformability and cell size. Conclusions. The automated rheoscope enables us to study the mechanical properties of RBCs more thoroughly by their deformability distribution. These deformability distributions are hardly influenced by the technique or by cell size. Show more

Keywords: Red blood cell, rheoscope, deformability distribution, ellipse, analysis

Citation: Biorheology, vol. 41, no. 2, pp. 65-77, 2004

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

Article Type: Research Article

Abstract: The effects of mechanical stress on red blood cell (RBC) deformability were evaluated by subjecting cells to a uniform fluid shear stress of 120 Pa for 15–120 seconds at 37°C. This level of stress induced significant impairment of RBC deformability as assessed by ektacytometry, with the degree of impairment independent of extracellular calcium concentration. Inhibition of RBC nitric oxide (NO) synthesis by a competitive inhibitor of NO synthases (N‐omega‐nitro‐L‐arginine methyl ester, L‐NAME) had no effect on deformability after exposure to mechanical stress. The NO donor sodium nitroprusside (SNP) prevented the deterioration of RBC deformability in a dose‐dependent manner with 10−4 …M being the most effective concentration. A similar protective effect by the non‐selective potassium channel blocker, tetraethylammonium chloride (TEA) suggests that the effect of NO might be mediated by the inhibition of potassium leakage from RBC. These results suggest that NO may prevent mechanical deterioration of RBC exposed to high shear stresses. While RBC are not exposed to such high levels of shear stresses for prolonged periods under normal circulatory conditions, comparable levels of mechanical stress can be encountered under certain situations (i.e., artificial organs, extracorporeal circulation) and may result in subhemolytic damage and hemorheological alterations. Show more

Keywords: Shear stress, erythrocyte deformability, mechanical damage, nitric oxide

Citation: Biorheology, vol. 41, no. 2, pp. 79-89, 2004

Authors: Rampling, M.W. | Meiselman, H.J. | Neu, B. | Baskurt, O.K.

Article Type: Research Article

Abstract: The reversible aggregation of red blood cells (RBC) into linear and three‐dimensional structures continues to be of basic science and clinical interest: RBC aggregation affects low shear blood viscosity and microvascular flow dynamics, and can be markedly enhanced in several clinical states. Until fairly recently, most research efforts were focused on relations between suspending medium composition (i.e., protein levels, polymer type and concentration) and aggregate formation. However, there is now an increasing amount of experimental evidence indicating that RBC cellular properties can markedly affect aggregation, with the term “RBC aggregability” coined to describe the cell's intrinsic tendency to aggregate. Variations …of aggregability can be large, with some changes of aggregation substantially greater than those resulting from pathologic states. The present review provides a brief overview of this topic, and includes such areas as donor‐to‐donor variations, polymer–plasma correlations, effects of RBC age, effects of enzymatic treatment, and current developments related to the mechanisms involved in RBC aggregation. Show more

Keywords: Aggregates, erythrocyte, polymers, rouleaux, surface properties

Citation: Biorheology, vol. 41, no. 2, pp. 91-112, 2004

Authors: Xu, Chun | Wootton, David M.

Article Type: Research Article

Abstract: Platelet margination (enhanced platelet concentration in the near wall region of a blood vessel) has been well documented in small vessels. In artery‐sized vessels margination has only been demonstrated in one study, using ghost cell suspensions and under relatively non‐physiologic conditions of steady flow and 50 cm development length. Local sampling experiments were performed to confirm platelet margination in artery‐sized stainless steel tubes, for a typical anatomical length and under pulsatile flow, using fresh EDTA‐anticoagulated porcine whole blood (N=21). Experiments were designed using three‐dimensional Computational Fluid Dynamics (CFD) to model the sample region with greater fidelity. Steady flow experiments in …50 cm long tubes verify published laser Doppler measurements of platelet margination in 3 mm ID tubes at normal arterial shear rate (500 s−1 ). Margination persists under pulsatile flow conditions (63.8 pulses/min), but in steady flow at length of 10 cm, margination is reduced. Platelet margination ratio (the ratio of the platelet concentration near the wall to bulk average platelet count) ranges from 1.21 to 2.48. No significant effects of calculated sampling thickness (20 μm and 50 μm) or pulsatility were detected. Hematocrit margination ratio is 0.68 to 0.90. Two model platelet concentration profiles are fit to the experimental results. Show more

Keywords: Margination, platelet concentration, local sampling, porcine model, thrombosis

Citation: Biorheology, vol. 41, no. 2, pp. 113-125, 2004

Authors: Zhu, Chu‐hong | Ying, Da‐jun | Mi, Jian‐hong | Zhu, Xing‐hong | Sun, Jian‐sen | Cui, Xiao‐ping

Article Type: Research Article

Abstract: In regions of a vessel that experience low shear stress and reversing flow patterns, early features in the pathogenesis of atherosclerosis include the accumulation of oxidized LDL (OxLDL) and adhesion of monocytes to endothelial cells (EC). Here we investigated the hypothesis that low shear stress (2 dyn/cm2 ) and OxLDL are synergistic for enhanced expression of vascular cell adhesion molecule (VCAM‐1) and human aortic endothelial cell (HAEC)–monocyte adhesion. This study shows low shear stress can significantly reduce IkappaBalpha levels, activate NF‐kappaB, increase the expression of VCAM‐1 in HAEC and binding of monocytes. OxLDL itself cannot significantly increase the expression of …VCAM‐1 in HAEC and binding of monocytes, but through activation of NF‐kappaB and degradation of IkappaBalpha induced by low shear stress it can significantly enhance VCAM‐1 expression and monocyte adhesion, over that in unmodified LDL or control. These results suggest that low shear stress can regulate monocyte adhesion to oxidized lipid‐induced endothelial cells via an IkappaBalpha‐dependent pathway, and that low shear stress together with OxLDL may likely play an important role in atherogenesis. Show more

Keywords: OxLDL, atherosclerosis, VCAM‐1, hemodynamics, IkappaBalpha

Citation: Biorheology, vol. 41, no. 2, pp. 127-137, 2004

Authors: McKean, Jason M. | Hsieh, Adam H. | Sung, K.L. Paul

Article Type: Research Article

Abstract: The anterior cruciate ligament (ACL) and the medial collateral ligament (MCL) are two commonly injured structures in the human knee. While the MCL heals post‐traumatically, the ACL does not. Since growth factors play a major role in the proliferation phase of wound healing, we compared the differential effects of epidermal growth factor (EGF) on adhesion and proliferation of ACL and MCL fibroblasts. Using a micropipette/micromanipulator system we found that cells subjected to shorter incubation periods (15 minutes) with EGF (5, 10, 50 ng/ml) showed a general increase in adhesion to the extracellular matrix fibronectin while cells subjected to longer incubation …periods (4, 6, 10, and 24 hr) with EGF (5 ng/ml) showed decreases in adhesion. For both incubation durations, MCL fibroblasts displayed a greater change in adhesion than ACL fibroblasts, when compared to control. Investigation of integrin expression showed no fluctuation in cell surface expression of the α5 subunit of the FN‐binding integrin α5 β1 for all EGF (5 ng/ml) incubation times. MCL cells showed a significant increase in proliferation upon stimulation with EGF compared to ACL cells when cultured in FN coated wells. The results found in this study help provide a better understanding of EGF's role in adhesion and proliferation, two events that may contribute to the differential healing response between ACL and MCL fibroblasts. Following exposure to EGF, ACL and MCL cells initially respond by increasing their adhesion strength. MCL cells respond to all concentrations of EGF while ACL cells appear to have a threshold concentration after which EGF effects plataeu. After this initial response period (<10 hr) cells exhibit lower adhesion strength and higher proliferation rate. It is possible that the release from FN serves to enhance the ability of the cells to proliferate. These results may aid in understanding the ligament healing process. Show more

Keywords: Growth factors, adhesion, integrins, ligament fibroblast

Citation: Biorheology, vol. 41, no. 2, pp. 139-152, 2004