H J Meiselman

Keck School of Medicine USC, Los Angeles, California, United States

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Publications (264)743.98 Total impact

  • Samar Rad, Herbert J Meiselman, Björn Neu
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    ABSTRACT: A theoretical framework based on macromolecular depletion has been utilized in order to examine the energetics of red blood cell interactions. Three different glycocalyx structures are considered and cell-cell affinities are calculated by superposition of depletion, steric and electrostatic interactions. The theoretical model predicts a non-monotonic dependence of the interaction energies on polymer size. Further, our results indicate that the glycocalyx segment distribution has a large impact on adhesion energies between cells: a linear segment distribution induces the strongest adhesion between cells followed by pseudo-tail and uniform distributions. Our approach confirms the concept of a depletion mechanism for RBC aggregation, and also provides new insights that may eventually help to understand and quantify cellular factors that control red blood cell interactions in health and disease.
    Colloids and surfaces B: Biointerfaces 09/2014; · 4.28 Impact Factor
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    ABSTRACT: Previous studies have demonstrated that red blood cells (RBC) either lyse or at least experience mechanical damage following prolonged exposure to high shear stress (≥100 Pa). Conversely, prolonged shear stress exposure within the physiological range (5-20 Pa, 300 s) was recently reported to improve RBC deformability. This study investigated the relationships between shear stress and RBC deformability to determine the breakpoint between beneficial vs. detrimental exposure to shear stress (i.e., "subhemolytic threshold"). A second aim of the study was to determine whether the frequency of intermittent application of shear stress influenced the subhemolytic threshold.METHODS: RBC were exposed to various levels of shear stress (0-100 Pa) in a Couette type shearing system for 300 s. RBC deformability was then immediately measured via ektacytometry. Parallel experiments were conducted at the same shear stresses, except the application time differed while keeping constant the total exposure time: shear stress was applied either for 30 s and repeated 10 times (10×30 s) or applied for 15 s and repeated 20 times (20×15 s).RESULTS: For a range of donors, the subhemolytic threshold with constant shear stress application was between 30-40 Pa. When physiological shear stress was applied in an intermittent manner, more frequent applications tended to improve (i.e., increase) RBC deformability. However, when supra-physiological shear stress was applied, both continuous and intermittent protocols damaged RBC. Changes of RBC mechanical behavior occurred without increases of hemoglobin in the suspending media, thus attesting to the absence of hemolysis.CONCLUSION: Shear stress has a biphasic effect on the mechanical properties of RBC, with the duration and rate of exposure appearing to have minimal impact on the subhemolytic threshold when compared with the magnitude of applied shear stress.
    Biorheology 06/2014; · 1.29 Impact Factor
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    ABSTRACT: BACKGROUND: Previous studies have demonstrated that red blood cells (RBC) either lyse or at least experience mechanical damage following prolonged exposure to high shear stress (≥100 Pa). Conversely, prolonged shear stress exposure within the physiological range (5–20 Pa, 300 s) was recently reported to improve RBC deformability. This study investigated the relationships between shear stress and RBC deformability to determine the breakpoint between beneficial vs. detrimental exposure to shear stress (i.e., “subhemolytic threshold”). A second aim of the study was to determine whether the frequency of intermittent application of shear stress influenced the subhemolytic threshold. METHODS: RBC were exposed to various levels of shear stress (0–100 Pa) in a Couette type shearing system for 300 s. RBC deformability was then immediately measured via ektacytometry. Parallel experiments were conducted at the same shear stresses, except the application time differed while keeping constant the total exposure time: shear stress was applied either for 30 s and repeated 10 times (10×30 s) or applied for 15 s and repeated 20 times (20×15 s). RESULTS: For a range of donors, the subhemolytic threshold with constant shear stress application was between 30–40 Pa. When physiological shear stress was applied in an intermittent manner, more frequent applications tended to improve (i.e., increase) RBC deformability. However, when supra-physiological shear stress was applied, both continuous and intermittent protocols damaged RBC. Changes of RBC mechanical behavior occurred without increases of hemoglobin in the suspending media, thus attesting to the absence of hemolysis. CONCLUSION: Shear stress has a biphasic effect on the mechanical properties of RBC, with the duration and rate of exposure appearing to have minimal impact on the subhemolytic threshold when compared with the magnitude of applied shear stress.
    Biorheology 06/2014; · 1.29 Impact Factor
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    ABSTRACT: Sickle cell disease (SCD) is characterized by decreased erythrocyte deformability, microvessel occlusion, and severe painful infarctions of different organs. Ektacytometry of SCD red blood cells (RBC) is made difficult by the presence of rigid, poorly-deformable irreversibly sickled cells (ISC) that do not align with the fluid shear field and distort the elliptical diffraction pattern seen with normal RBC. In operation, the computer software fits an outline to the diffraction pattern, then reports an elongation index (EI) at each shear stress based on the length and width of the fitted ellipse: EI=(length-width)/(length+width). Using a commercial ektacytometer (LORCA, Mechatronics Instruments, Netherlands) we have approached the problem of ellipse fitting in two ways: (1) altering the height of the diffraction image on a computer monitor using an aperture within the camera lens; (2) altering the light intensity level (gray level) used by the software to fit the image to an elliptical shape. Neither of these methods affected deformability results (elongation index-shear stress relations) for normal RBC but did markedly affect results for SCD erythrocytes: (1) decreasing image height by 15% and 30% increased EI at moderate to high stresses; (2) progressively increasing the light level increased EI over a wide range of stresses. Fitting data obtained at different image heights using the Lineweaver-Burke routine yielded percentage ISC results in good agreement with microscopic cell counting. We suggest that these two relatively simple approaches allow minimizing artifacts due to the presence of rigid discs or ISC and also suggest the need for additional studies to evaluate the physiological relevance of deformability data obtained via these methods.
    Biorheology 06/2014; · 1.29 Impact Factor
  • Björn Neu, Herbert J Meiselman
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    ABSTRACT: If a surface is in contact with a solution containing macromolecules or proteins, and the loss of configurational entropy of these molecules at the surface is not balanced by adsorption energy, a polymer-poor layer will develop near the surface. If two such layers overlap, an attractive force develops due to the osmotic pressure difference between these depletion zones and the bulk phase. Recent studies have shown that depletion interaction plays a major role in red blood cell (RBC) aggregation and hence it is a major determinate of blood flow stability; depletion interaction also markedly affects RBC adhesion to vascular endothelial cells. Understanding and quantitating factors that regulate depletion in vivo are thus of importance, yet made difficult since only very small changes of the cell surface (e.g., glycocalyx thickness) such as seen during RBC aging can lead to massive changes of depletion interaction and hence cell-cell adhesion. It is suggested that insight into the in vivo relevance of depletion mechanisms may lead to an improved understanding of how and why blood flow is altered in many diseases, and may also provide new biomarkers (e.g., surface properties) that will aid in the development of novel or improved diagnostic and therapeutic tools.
    Biorheology 05/2014; · 1.29 Impact Factor
  • Yang Yang, Stephanie Koo, Li Tze Heng, Herbert J Meiselman, Björn Neu
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    ABSTRACT: Abnormal adhesion of red blood cells (RBCs) to vascular endothelium is often associated with reduced levels of sialic acid on RBC membranes and with elevated levels of pro-adhesive plasma proteins. However, the synergistic effects of these two factors on the adhesion are not clear. In this work, we tested the hypothesis that macromolecular depletion interaction originating from non-adsorbing macromolecules can promote the adhesion of RBC with reduced sialic acid content to the endothelium. RBCs are treated with neuraminidase to specifically remove sialic acids from their surface followed by the evaluation of their deformability, zeta potential and membrane proteins. The adhesion of these enzyme-treated RBCs to cultured human umbilical vein endothelial cells (ECs) is studied in the presence of 70 or 500 kDa dextran with a flow chamber assay. Our results demonstrate that removal of sialic acids from RBC surface can induce erythrocyte adhesion to endothelial cells and that such adhesion is significantly enhanced in the presence of high molecular weight dextran. The adhesion-promoting effect of dextran exhibits a strong dependence on dextran concentration and molecular mass, and it is concluded to originate from macromolecular depletion interaction. These results suggest that elevated levels of non-adsorbing macromolecules in plasma might play a significant role in promoting endothelial adhesion of erythrocytes with reduced sialic acids. Our findings should therefore be of great value in understanding abnormal RBC-EC interactions in pathophysiological conditions (e.g., sickle cell disease and diabetes) and after blood transfusions.
    Biochimica et Biophysica Acta 09/2013; · 4.66 Impact Factor
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    Michael J Simmonds, Herbert J Meiselman, Oguz K Baskurt
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    ABSTRACT: The flow properties of blood play significant roles in tissue perfusion by contributing to hydrodynamic resistance in blood vessels. These properties are influenced by pathophysiological processes, thereby increasing the clinical relevance of blood rheology information. There is well-established clinical evidence for impaired blood fluidity in humans of advanced age, including enhanced plasma and whole blood viscosity, impaired red blood cell (RBC) deformability and enhanced RBC aggregation. Increased plasma fibrinogen concentration is a common finding in many studies owing to the pro-inflammatory condition of aged individuals; this finding of increased fibrinogen concentration explains the higher plasma viscosity and RBC aggregation in elderly subjects. Enhanced oxidant stress in advanced age is also known to contribute to altered blood fluidity, with RBC deformability being an important determinant of blood viscosity. Several studies have shown that physical activity may improve the hemorheological picture in elderly subjects, yet well-designed observational and mechanistic studies are required to determine the specific effects of regular exercise on hemorheological parameters in healthy and older individuals.
    Journal of Geriatric Cardiology 09/2013; 10(3):291-301.
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    ABSTRACT: Autologous hematopoietic stem cell gene therapy is an approach to treating sickle cell disease (SCD) patients that may result in lower morbidity than allogeneic transplantation. We examined the potential of a lentiviral vector (LV) (CCL-βAS3-FB) encoding a human hemoglobin (HBB) gene engineered to impede sickle hemoglobin polymerization (HBBAS3) to transduce human BM CD34+ cells from SCD donors and prevent sickling of red blood cells produced by in vitro differentiation. The CCL-βAS3-FB LV transduced BM CD34+ cells from either healthy or SCD donors at similar levels, based on quantitative PCR and colony-forming unit progenitor analysis. Consistent expression of HBBAS3 mRNA and HbAS3 protein compromised a fourth of the total β-globin-like transcripts and hemoglobin (Hb) tetramers. Upon deoxygenation, a lower percentage of HBBAS3-transduced red blood cells exhibited sickling compared with mock-transduced cells from sickle donors. Transduced BM CD34+ cells were transplanted into immunodeficient mice, and the human cells recovered after 2-3 months were cultured for erythroid differentiation, which showed levels of HBBAS3 mRNA similar to those seen in the CD34+ cells that were directly differentiated in vitro. These results demonstrate that the CCL-βAS3-FB LV is capable of efficient transfer and consistent expression of an effective anti-sickling β-globin gene in human SCD BM CD34+ progenitor cells, improving physiologic parameters of the resulting red blood cells.
    The Journal of clinical investigation 07/2013; · 15.39 Impact Factor
  • Oguz K Baskurt, Herbert J Meiselman
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    ABSTRACT: Red blood cells (RBC) are exposed to various levels of shear stress (SS) during their flow in the circulatory system, yet no significant damage occurs if their mechanical stability is not impaired. Alternatively, normal RBC may be damaged during flow in non-physiological environments and under extreme SS (e.g., extracorporeal circulation, ventricular assist devices). The shear-induced damage may result in hemolysis or altered mechanical properties of RBC that, in turn, reduces the ability of RBC to withstand further damage by SS. An ektacytometer employing a Couette shearing system was used to apply 100 Pa constant level of SS for 300 seconds as a model of sub-hemolytic mechanical stress. The degree of cellular damage during and after the application was assessed by diffraction pattern analysis. The area of the diffraction pattern was found to correlate with the number of RBC in the sheared suspension. Monitoring the ellipse area during the application of gradually increasing SS provides the concentration of the remaining intact RBC, therefore can be used to estimate the hemolytic threshold as a measure of RBC mechanical stability. Hemolytic threshold determined after the mechanical stress application was found to be ~150 Pa, while it was ~250 Pa in the same samples before the SS application. Additionally, SS-elongation index curves recorded before and after the application of the sub-hemolytic SS significantly differed from each other, indicating the impairment in deformability following the mechanical stress. The Couette type ektacytometer can be used as a tool to assess the sub-hemolytic damage to RBC in testing the biomedical equipment.
    Clinical hemorheology and microcirculation 02/2013; · 3.40 Impact Factor
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    ABSTRACT: Cardiovascular diseases (CVD) are the most frequent cause of death throughout the world. The coronary vessel system is a special part of the circulation since there is a continuous change in blood flow, perfusion pressure and shear rate during each cardiac cycle. It is also the place of the narrowest capillaries in the human body, therefore the role of rheological alterations may be of greater importance than in the other parts of the circulatory system. During the past decades, our group has investigated hemorheological parameters (HP) in over 1,000 patients diagnosed with various forms of ischemic heart disease (IHD). In one prospective study, we measured the HP of patients with acute coronary syndrome (ACS). On admission, all examined variables were significantly worse than those of control subjects. During the hospital phase, some of the HP showed further deterioration, and HP remained in the pathologic range during the follow-up period. In another study, we showed that HP are in close correlation with the severity of coronary artery disease. In patients treated with percutaneous coronary intervention, changes in HP were very similar to those observed in subjects with ACS. In a recent study, we analyzed HP in patients undergoing CABG surgery. Our data suggest a hemorheological advantage of off-pump surgery. In another study low Hct/WBV ratio can be regarded as a risk factor of cardiac death in IHD. Our data indicate that rheological parameters are significantly altered in patients with IHD: the extent of the alterations is in excellent correlation with the clinical severity of the disease. Our findings prove that HP play a critical role in the pathogenesis of myocardial ischemia. In recent in vitro and in vivo studies we have investigated the effects of red wine on hemorheological parameters. Our results show that moderate red wine consumption has beneficial effects on hemorheological parameters which may contribute to the French paradox.
    Clinical hemorheology and microcirculation 02/2013; · 3.40 Impact Factor
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    ABSTRACT: Classically, it is known that red blood cell (RBC) deformability is determined by the geometric and material properties of these cells. Experimental evidence accumulated during the last decade has introduced the concept of active regulation of RBC deformability. This regulation is mainly related to altered associations between membrane skeletal proteins and integral proteins, with the latter serving to anchor the skeleton to the lipid matrix. It has been hypothesized that shear stress induces alterations of RBC deformability: the current study investigated the dynamics of the transient improvement in deformability induced by shear stress at physiologically-relevant levels. RBC were exposed to various levels of shear stress (SS) in a Couette type shearing system that is part of an ektacytometer, thus permitting the changes in RBC deformability during the application of SS to be monitored. Initial studies showed that there is an increase in deformability of the RBC subjected to SS in the range of 5-20 Pa, with kinetics characterized by time constants of a few seconds. Such improvement in deformability, expressed by an elongation index (EI), was faster with higher levels of SS and hence yielded shorter time constants: absolute values of EI increased by 3-8% of the starting level. Upon the removal of the shear stress, this response by RBC was reversible with a slower time course compared to the increase in EI during application of SS. Increased calcium concentration in the RBC suspending medium prevented the improvement of deformability. It is suggested that the improvement of RBC deformability by shear forces may have significant effects on blood flow dynamics, at least in tissues supplied by blood vessels with impaired vasomotor reserve, and may therefore serve as a compensating mechanism for the maintenance of adequate microcirculatory perfusion.
    Biorheology 01/2013; 50(3):165-76. · 1.29 Impact Factor
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    ABSTRACT: The role of membrane fluidity in determining red blood cell (RBC) deformability has been suggested by a number of studies. The present investigation evaluated alterations of RBC membrane fluidity, deformability and stability in the presence of four linear alcohols (methanol, ethanol, propanol and butanol) using ektacytometry and electron paramagnetic resonance (EPR) spectroscopy. All alcohols had a biphasic effect on deformability such that it increased then decreased with increasing concentration; the critical concentration for reversal was an inverse function of molecular size. EPR results showed biphasic changes of near-surface fluidity (i.e., increase then decrease) and a decreased fluidity of the lipid core; rank order of effectiveness was butanol > propanol > ethanol > methanol, with a significant correlation between near-surface fluidity and deformability (r = 0.697; p<0.01). The presence of alcohol enhanced the impairment of RBC deformability caused by subjecting cells to 100 Pa shear stress for 300 s, with significant differences from control being observed at higher concentrations of all four alcohols. The level of hemolysis was dependent on molecular size and concentration, whereas echinocytic shape transformation (i.e., biconcave disc to crenated morphology) was observed only for ethanol and propanol. These results are in accordance with available data obtained on model membranes. They document the presence of mechanical links between RBC deformability and near-surface membrane fluidity, chain length-dependence of the ability of alcohols to alter RBC mechanical behavior, and the biphasic response of RBC deformability and near-surface membrane fluidity to increasing alcohol concentrations.
    PLoS ONE 01/2013; 8(9):e76579. · 3.53 Impact Factor
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    ABSTRACT: Elevated red blood cell (RBC) aggregation increases low-shear blood viscosity and is closely related to several pathophysiological diseases such as atherosclerosis, thrombosis, diabetes, hypertension, cancer, and hereditary chronic hemolytic conditions. Non-ionic linear polymers such as poly(ethylene glycol) (PEG) and Pluronic F68 have shown inhibitory effects against RBC aggregation. However, hypersensitivity reactions in some individuals, attributed to a diblock component of Pluronic F68, have been reported. Therefore, we investigated the use of an amphiphilic star-shaped PEG polymer based on a cholic acid core as a substitute for Pluronics to reduce RBC aggregation. Cholic acid is a natural bile acid produced in the human liver and therefore should assure biocompatibility. Cholic acid based PEG polymers, termed CA(PEG)(4), were synthesized by anionic polymerization. Size exclusion chromatography indicated narrow mass distributions and hydrodynamic radii less than 2nm were calculated. The effects of CA(PEG)(4) on human RBC aggregation and blood viscosity were investigated and compared to linear PEGs by light transmission aggregometry. Results showed optimal reduction of RBC aggregation for molar masses between 10 and 16kDa of star-shaped CA(PEG)(4) polymers. Cholic acid based PEG polymers affect the rheology of erythrocytes and may find applications as alternatives to linear PEG or Pluronics to improve blood fluidity.
    Journal of the mechanical behavior of biomedical materials. 11/2012; 18C:100-107.
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    ABSTRACT: BACKGROUND: Chronic transfusion therapy (CTT) is a mainstay for stroke prophylaxis in sickle cell anemia, but its effects on hemodynamics are poorly characterized. Transfusion improves oxygen-carrying capacity, reducing demands for high cardiac output, while decreasing hemoglobin (Hb)S%, reticulocyte count, and hemolysis. We hypothesized that transfusion would improve oxygen-carrying capacity, but that would be counteracted by a decrease in cardiac output due to increased hematocrit (Hct) and vascular resistance, leaving oxygen delivery unchanged. STUDY DESIGN AND METHODS: To test this hypothesis, we examined patients on CTT immediately before transfusion and again 12 to 120 hours after transfusion, using echocardiography and near infrared spectroscopy. RESULTS: Comparable increases in Hb and Hct and decreases in reticulocyte count and HbS with transfusion were observed in all patients, but males had a larger rebound of HbS%, reticulocyte count, and free Hb levels between transfusions. In males, transfusion decreased heart rate by 12%, stroke volume by 15%, and cardiac index by 24% while estimates for pulmonary and systemic vascular resistance increased, culminating in 6% decrease in oxygen delivery. In contrast, stroke volume and cardiac index and systemic and pulmonary vascular resistance did not change in women after transfusion, such that oxygen delivery improved 17%. CONCLUSION: In our sample population, males exhibit a paradoxical reduction in oxygen delivery in response to transfusion because the increase in vascular resistance is larger than the increase in oxygen capacity. This may result from an inability to adequately suppress their HbS% between transfusion cycles.
    Transfusion 11/2012; · 3.53 Impact Factor
  • Oguz K Baskurt, Herbert J Meiselman
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    ABSTRACT: Laser-diffraction ektacytometry is a generally accepted technique for measuring RBC deformability induced by fluid shear stress (SS) and yields paired elongation index-SS data at several levels of stress. Unfortunately, comparison of results is hindered by the lack of simple indices that accurately characterize these data. Several mathematical models have been proposed, including those developed for analysis of enzyme kinetics (Lineweaver-Burk, Eadie-Hofstee) and curve fitting (Streekstra-Bronkhorst). All of these analytical approaches provide a value for cell deformation at infinite stress (EImax) and the shear stress required to achieve one-half of this deformation (SS1/2); the use of non-linear regression is essential when calculating these parameters. While the current models provide equivalent results for normal RBC if used with non-linear regression, EImax and SS1/2 are not always concordant for cells with abnormal mechanical behavior. This technical note examines such differences for three conditions: glutaraldehyde treatment, mechanical stress and non-isotonic media. It was found that none of the models yield completely satisfactory values for EImax and SS1/2, especially if there are large changes of EImax. However, the ratio of SS1/2 to EImax (SS1/2/EImax) is much less affected by these problems, has similar power (i.e., standardized difference) as SS1/2 and EImax and is more robust in reflecting alterations of deformability. We thus conclude that the SS1/2/EImax ratio can be used when reporting and comparing various populations of RBC or cells obtained from subjects having different clinical states.
    Clinical hemorheology and microcirculation 10/2012; · 3.40 Impact Factor
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    ABSTRACT: Consumption of red wine is associated with a decreased risk of several cardiovascular diseases (e.g., coronary artery disease, stroke), but unfortunately literature reports regarding ethanol's effects on hemorheological parameters are not concordant. In the present study, red blood cell (RBC) deformability was tested via laser ektacytometry (LORCA, 0.3-30 Pa) using two approaches: 1) addition of ethanol to whole blood at 0.25%-2% followed by incubation and testing in ethanol-free LORCA medium; 2) addition of ethanol to the LORCA medium at 0.25%-6% then testing untreated native RBC in these media. The effects of ethanol on deformability for oxidatively stressed RBC were investigated as were changes of RBC aggregation (Myrenne Aggregometer) for cells in autologous plasma or 3% 70 kDa dextran. Significant dose-related increases of RBC deformability were observed at 0.25% (p < 0.05) and higher concentrations only if ethanol was in the LORCA medium; no changes occurred for cells previously incubated with ethanol then tested in ethanol-free medium. The impaired deformability of cells pre-exposed to oxidative stress was improved only if ethanol was in the LORCA medium. RBC aggregation decreased with concentration at 0.25% and higher for cells in both autologous plasma and dextran 70. Our results indicate that ethanol reversibly improves erythrocyte deformability and irreversibly decreases erythrocyte aggregation; the relevance of these results to the health benefits of moderate wine consumption require further investigation.
    Clinical hemorheology and microcirculation 10/2012; · 3.40 Impact Factor
  • Oguz K Baskurt, Herbert J Meiselman
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    ABSTRACT: Red blood cell (RBC) aggregate to form two- and three-dimensional structures when suspended in aqueous solutions containing large plasma proteins or polymers; this aggregation is reversible and shear dependent (i.e., dispersed at high shear and reformed at low or stasis). The extent of aggregation is the main determinant of low shear blood viscosity, thus predicting an inverse relationship between aggregation and in vivo blood flow. However, the effects of aggregation on hemodynamic mechanisms (e.g., plasma skimming, Fåhraeus Effect, microvascular hematocrit) may promote rather than impede vascular blood flow. The impact of enhanced RBC aggregation on endothelial function and hemostatic mechanisms adds further complexity, thereby requiring specific attention to the nature, extent and time course of aggregation when considering its overall influence on tissue perfusion. A detailed understanding of aggregation effects is important from a clinical point of view since it may be enhanced during a variety of pathophysiological processes, including infections, circulatory and metabolic disorders, hematological pathologies and several other disease states. Altered RBC aggregation may be an indicator of disease as well as a factor affecting the course of the clinical condition; the prognostic value of RBC aggregation indices has been demonstrated in various diseases. Currently, RBC aggregation is an easily and accurately measurable parameter, and therefore may be expected to have broader clinical usage in the future.
    Clinical hemorheology and microcirculation 09/2012; · 3.40 Impact Factor
  • Oguz K Baskurt, Herbert J Meiselman
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    ABSTRACT: Comparative data on blood composition and blood flow properties indicate different levels of interspecies variation for several parameters. Hematocrit and hemoglobin levels have relatively low variability among mammals, while mean cell volume and red blood cell (RBC) count are more variable. There is also a difference of variability between high and low shear rate blood viscosity in mammals, with low shear rate viscosity having a higher degree of interspecies variation. This observation parallels the diversity of RBC aggregation among mammalian species. Allometric relations for blood rheology parameters indicate highly significant correlations of low shear rate blood viscosity and RBC aggregation with body weight, especially if species belonging to the order Artiodactyla are excluded. These allometric relations can be used to formulate various hypotheses about the evolutionary histories of circulatory functions, as well as hypotheses related to the role of RBC aggregation in the mammalian circulatory system. Such comparative studies and analytical reasoning based on comparative data may contribute to answering the "why" questions, and accordingly may improve our understanding of circulatory functions and hence may have possible clinical importance. During the last several decades, similar approaches to various medical concepts have yielded a new approach to medicine that is now known as Evolutionary Medicine.
    Clinical hemorheology and microcirculation 09/2012; · 3.40 Impact Factor
  • Oguz K Baskurt, Herbert J Meiselman
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    ABSTRACT: It is well known that hemostatic-thrombotic mechanisms are influenced by hemodynamic factors, such as shear forces affecting platelets or red blood cell aggregation, in turn affecting flow in stenotic regions. Endothelial cell function is also significantly influenced by shear forces acting on the vessel wall. Further, the distribution of shear forces in the vasculature is complex and closely associated with factors determining the flow properties of blood. Therefore, there is a link among alterations in the rheological properties of blood and its elements and the risk for thrombosis, with this linkage confirmed by numerous clinical studies. After discussing relevant rheological and hemodynamic concepts, this review focuses on selected drug-induced conditions that are known to be associated with both hyperviscosity conditions and increased thrombotic risk: oral contraceptives, diuretics, intravenous immunoglobulin, erythropoiesis-stimulating agents, chemotherapy, and radio-contrast media. Alterations of relationships between blood rheology and thrombotic risk related to artificial circulatory environments and physical exercise are also briefly discussed.
    Seminars in Thrombosis and Hemostasis 08/2012; · 4.22 Impact Factor
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    ABSTRACT: BACKGROUND: Simple chronic transfusion therapy (CTT) is a mainstay for stroke prophylaxis in sickle cell anemia, but its effects on hemodynamics are poorly characterized. Transfusion improves oxygen-carrying capacity, reducing demands for high cardiac output. While transfusion decreases factors associated with vasoocclusion, including percent hemoglobin (Hb)S, reticulocyte count, and circulating cell-free Hb, it increases blood viscosity, which reduces microvascular flow. The hematocrit-to-viscosity ratio (HVR) is an index of red blood cell oxygen transport effectiveness that varies with shear stress and balances the benefits of improved oxygen capacity to viscosity-mediated impairment of microvascular flow. We hypothesized that transfusion would improve HVR at high shear despite increased blood viscosity, but would decrease HVR at low shear. STUDY DESIGN AND METHODS: To test this hypothesis, we examined oxygenated and deoxygenated blood samples from 15 sickle cell patients on CTT immediately before transfusion and again 12 to 120 hours after transfusion. RESULTS: Comparable changes in Hb, hematocrit (Hct), reticulocyte count, and HbS with transfusion were observed in all subjects. Viscosity, Hct, and high-shear HVR increased with transfusion while low-shear HVR decreased significantly. CONCLUSION: Decreased low-shear HVR suggests impaired oxygen transport to low-flow regions and may explain why some complications of sickle cell anemia are ameliorated by CTT and others may be made worse.
    Transfusion 08/2012; · 3.53 Impact Factor

Publication Stats

3k Citations
743.98 Total Impact Points

Institutions

  • 1990–2014
    • Keck School of Medicine USC
      Los Angeles, California, United States
    • University of California, Irvine
      • Department of Physiology & Biophysics
      Irvine, CA, United States
  • 1985–2014
    • University of Southern California
      • • Department of Physiology and Biophysics
      • • Department of Biomedical Engineering
      • • Department of Neurology
      Los Angeles, California, United States
  • 2013
    • Griffith University
      • Centre for Heart Foundation Research
      Southport, Queensland, Australia
  • 2011–2013
    • Koc University
      • School of Medicine
      İstanbul, Istanbul, Turkey
  • 2007–2013
    • Nanyang Technological University
      • • School of Chemical and Biomedical Engineering
      • • Division of Bioengineering (BIE)
      Singapore, Singapore
  • 1983–2013
    • University of California, Los Angeles
      • Department of Ophthalmology
      Los Angeles, California, United States
  • 2012
    • Université de Montréal
      Montréal, Quebec, Canada
  • 2011–2012
    • Children's Hospital Los Angeles
      Los Angeles, California, United States
  • 2000–2012
    • University of Pécs
      Fuenfkirchen, Baranya county, Hungary
  • 2000–2011
    • Akdeniz University
      • Department of Physiology
      Antalya, Antalya, Turkey
  • 2006–2010
    • University of Alaska Fairbanks
      • Institute of Marine Science
      Fairbanks, AK, United States
  • 2009
    • Centre hospitalier de l'Université de Montréal (CHUM)
      Montréal, Quebec, Canada
  • 2007–2009
    • University of Debrecen
      • • Institute of Surgery
      • • Department of Operative Techniques and Surgical Research
      Debrecen, Hajdu-Bihar, Hungary
  • 2002–2006
    • Jules Stein Eye Institute
      Maryland, United States
  • 2004
    • Imperial College London
      Londinium, England, United Kingdom
  • 1999–2004
    • Ben-Gurion University of the Negev
      • • Faculty of Health Sciences
      • • Department of Chemistry
      Beersheba, Southern District, Israel
  • 2001
    • University of Tennessee
      • Department of Pathobiology
      Knoxville, TN, United States
  • 1992–1997
    • Umeå University
      Umeå, Västerbotten, Sweden
  • 1993
    • Helsinki University Central Hospital
      Helsinki, Southern Finland Province, Finland
    • Universität Heidelberg
      • Department of Neonatology
      Heidelburg, Baden-Württemberg, Germany
  • 1991
    • University of Birmingham
      Birmingham, England, United Kingdom