Clinical Hemorheology and Microcirculation - Volume 64, issue 4

Authors: Brun, Jean-Frédéric | Varlet-Marie, Emmanuelle | Fédou, Christine | Raynaud de Mauverger, Eric

Article Type: Research Article

Abstract: We investigated to what extent a prediction of the ‘ideal’ hematocrit based on individual hemorheological profile with an equation of viscosity is relevant in trained athletes, and how the agreement between theoretical and actual values is modified by changes in training volume and performance. Elite soccer players (national level: 18–32 yr, weight 61–83 kg, body mass index 20.9–25.8 kg/m2 ) were seen twice at one year interval. Hemorheologic parameters were measured with the MT90 viscometer and the Myrenne aggregometer the theoretical bell-shaped curve of hematocrit/viscosity ratio as a function of hematocrit was reconstructed with Quemada’s equation using actual plasma viscosity and red cell rigidity to …predict hematocrit/viscosity at various hematocrit levels. RBC aggregation is correlated at baseline with fat mass (M1 = 0.552 p  < 0.02) and changes in aggregation are related to changes in fat mass (M = 0.652, p  < 0.05; M1 = 0.647, p  < 0.05). Predicted and actual hematocrit are correlated (r  = 0.644, p  < 0.05) but exhibit discrepancies (mean difference –1% range [3.24 to 1.24]) and those discrepancies are inversely correlated to the level of predicted hematocrit (r  = –0.912, p  < 0.01), to systolic blood pressure (r  = –0.626, p  < 0.05), and to the overtraining score (r  = –0.693, p  < 0.05). After one year changes in hematocrit are a close reflect of the change in training volume (r  = –0.877, p  < 0.01) but are not correlated to fitness changes. Therefore in these athletes i) systemic hematocrit is close to its predicted ‘ideal value”, suggesting the accuracy of the prediction; ii) red cell aggregation is correlated to fat mass even in nonobese subjects; iii) hematocrit is lower than predicted by the model when markers of sympathetic tone (systolic blood pressure, overtraining score) are increased; iv) weekly training volume appears the main determinant of the reduction of hematocrit. Show more

Keywords: Exercise, soccer, hematocrit/viscosity ratio, hemorheology, erythrocyte aggregation

DOI: 10.3233/CH-168014

Citation: Clinical Hemorheology and Microcirculation, vol. 64, no. 4, pp. 799-808, 2016

Authors: Joré, Céline | Brun, Jean-Frédéric | Varlet-Marie, Emmanuelle

Article Type: Research Article

Abstract: Erythropoietin (EPO) is a major regulator of blood viscosity. Its long lasting action analogue methoxy polyethylene glycol-epoetin-β (MIRCERA® ) seems to be also employed in modern doping. We took the opportunity of a study aiming at developing a detection of recent MIRCERATM injection in the context of doping detection to assess the effects of this EPO analogue on red blood cells (RBC) aggregation. A single dose 200 μg of MIRCERA® was injected to 10 male volunteers and blood samplings were drawn over 24 days. After injection a decrease in mean corpuscular volume at day 2 (p  < 0.01) and day 10 (p  < 0.02), a rise …in reticulocyte count (p  < 0.001) between day 4 and day 17 and a decrease in ferritin a day 5 (p  < 0.05) was observed. Hemoglobin decreased at day 4 (p  < 0.005). Hematocrit was unchanged. There was a dramatic (+67%) increase in RBC aggregation index “M” (from 9.49±1.01 to 17.66±1.8, p  < 0.01). A decrease in systolic blood pressure was observed during the period from day 4 to day 17 (at day 10: –11.90±2.28 mmHg, p  < 0.001; at day 17: –15.80±2.83, p  < 0.001). There was also a decrease in diastolic blood pressure, mean and pulse pressure. Correlations between this decrease in blood pressure and “M” did not reach significance but pulse pressure was positively correlated to “M” (r  = 0.743, p  < 0.05). These data show that the long acting erythropoietin analogue MIRCERA® strongly increases RBC aggregation parallel to a decrease in blood pressure, but a possible causative link between the two events is not clearly evidenced. Show more

Keywords: Blood viscosity, hematocrit, exercise, erythrocyte deformability

DOI: 10.3233/CH-168015

Citation: Clinical Hemorheology and Microcirculation, vol. 64, no. 4, pp. 809-816, 2016

Authors: Varlet-Marie, Emmanuelle | Brun, Jean-Frédéric | Raynaud de Mauverger, Eric | Fédou, Christine

Article Type: Research Article

Abstract: We investigated whether the concept of hematocrit/viscosity (h/η ) ratio explains the “paradox of hematocrit in athletes”, by calculating a “theoretical optimal hematocrit” (i.e., associated with the higher h/η value predicted with Quemada’s equation from plasma viscosity, and erythrocyte rigidity index) before and after exercise. 14 rugby players (19–31 yr; weight 65.8–109.2 kg; height 1.7–1.96 m; BMI 21.7–33.1 kg/m2 ) underwent a standardized submaximal exercise session on cycloergometer corresponding to 225 kjoules over 30 min. The rheologic response to exercise was measured with the MT90 viscometer and the Myrenne aggregometer. After exercise there was an increase in whole blood viscosity (p  < 0.05) …and hematocrit (p  < 0.005) and a decrease in h/η ratio (from 14.7±0.34 to 12.9±0.37, p  < 0.005). There was an increase in viscometric RBC rigidity indexes “Tk” and “k” in 9/14 subjects. Predicted and actual h/η are fairly well correlated (preexercise r  = 0.998, p  < 0.001; postexercise r  = 0.985 p  < 0.001) but actual h/η was lower than predicted (preexercise p  = 0.005; postexercise p  = 0.02). This discrepancy between predicted and measured hematocrit was not correlated to dehydration or plasma viscosity but was correlated to red cell rigidity (r  = 0.774, p  < 0.01) and its exercise-induced change (r  = 0.858, p  < 0.01). This study suggests that h/η , although it is not directly correlated to parameters of exercise performance, is precisely regulated during exercise according to the classic concept of “viscoregulation”, and that the prediction of the theoretical optimal values of h/η and hematocrit by models may help to interpret the actual values of these parameters. However, these models need to be more extendedly tested and improved. Show more

Keywords: Blood viscosity, hematocrit, exercise, rugby, erythrocyte deformability

DOI: 10.3233/CH-168042

Citation: Clinical Hemorheology and Microcirculation, vol. 64, no. 4, pp. 817-826, 2016

Authors: Ahmadizad, Sajad | Bassami, Minoo | Hadian, Mohsen | Eslami, Maryam

Article Type: Research Article

Abstract: BACKGROUND: Acute effects of continuous exercise on the markers of blood fluidity have been addressed in different populations and the changes are intensity related. However, the effect of different high intensity interval exercise (HIIE) on these variables is unclear. OBJECTIVE: This study is designed to determine the effects of two different HIIE with different work/rest ratios but the same energy expenditure on the main determinants of blood fluidity. METHODS: Ten overweight men (age, 26.3±1.7 yrs) completed two HIIE protocols on two separate occasions with one week intervening. The two HIIE encompassed performing: 1) 6 intervals …of 2 min activity at 85% of VO2max interspersed by 2 min active recovery at 30% of VO2max (ratio 1 to 1, HIIE1/1 ), and 2) 6 intervals of 30 s activity at 110% of VO2max interspersed by 4 min active recovery at 40% of VO2max (ratio 1 to 8, HIIE1/8 ). Each exercise trial was followed by 30 min rest. Venous blood samples were obtained before exercise, immediately after exercise and after recovery and analyzed for blood and plasma viscosity, fibrinogen and red blood cell indices. RESULTS: The HIIE1/1 protocol led to higher reduction (P  < 0.01) in plasma volume changes compared to HIIE1/8 (9.9% vs 5.7%). Moreover, increases in blood viscosity, plasma viscosity, hematocrit, RBC count and mean arterial blood pressure observed following HIIE1/1 were significantly (P  < 0.05) higher than HIIE1/8 ; whereas, the changes in fibrinogen concentration neither were significant in response to both trials nor were significantly different between two protocols (P  > 0.05). However, the changes in all variables during exercise were transient and returned to the baseline levels after 30 min recovery. CONCLUSIONS: It is concluded that the HIIE protocol with lower intensity and shorter rest intervals (higher work to rest ratio) clearly results in more physiological strain than HIIE with higher intensity but longer rest intervals (lower work to rest ratio) in overweight individuals, and that the work to rest ratio could be as important as exercise intensity when considering the hemorheological variables during HIIE. Show more

Keywords: Interval exercise, exercise intensity, blood viscosity, fibrinogen

DOI: 10.3233/CH-168009

Citation: Clinical Hemorheology and Microcirculation, vol. 64, no. 4, pp. 827-835, 2016

Authors: Antonova, N. | Tsiberkin, K. | Podtaev, S. | Paskova, V. | Velcheva, I. | Chaushev, N.

Article Type: Research Article

Abstract: The aim of the study is to investigate the changes of the skin blood flow responses to cold stress in patients with diabetes mellitus type 2 through wavelet analysis of the peripheral skin temperature oscillations and to estimate their relationship with the blood viscosity values. The amplitudes of the skin temperature pulsations (ASTP) were monitored by “Microtest” device (“FM-Diagnostics”, Russia); the whole blood viscosity and the shear stresses were measured by Contraves LS30 viscometer (Switzerland) at a steady flow in 9 healthy subjects and in 30 patients with type 2 diabetes mellitus. Power law and Herschel-Bulkley (HB) equations were applied …to describe the blood rheology. Both models include consistency (k ) and flow index (m ), and the HB also gives the yield stress (τ 0 ). The Spearman rank correlations between these parameters and the ASTP in the frequency ranges, corresponding to the myogenic, neurogenic and endothelial mechanisms of the microcirculation tone regulation were calculated. The ASTP values decreased when the blood viscosity increased. The correlation analysis revealed good ASTP–m (r  > 0.5) and ASTP–k (r  < –0.5) relationships in the endothelial range, while the ASTP–τ 0 correlation was weaker (r ≈–0.4). These correlations became lower for the ASTP during the cold stress. The results prompt manifestation of endothelial dysfunction in patients with type 2 diabetes. Show more

Keywords: Diabetes mellitus type 2, skin temperature oscillations, contralateral cold test, microcircular tone regulation, blood viscosity, hemorheological equations

DOI: 10.3233/CH-168000

Citation: Clinical Hemorheology and Microcirculation, vol. 64, no. 4, pp. 837-844, 2016

Authors: Jovtchev, S. | Alexandrov, S. | Hristova-Avakumova, N. | Miteva, S. | Traikov, L. | Gerasimova, D. | Stoeff, S.

Article Type: Research Article

Abstract: BACKGROUND: Different colloids are used as a part of solutions for fluid resuscitation and organ preservation: hydroxyethyl starches (HES), dextran (Dx), polyethylene glycols (PEG), polyvinyl pyrrolidone (PVP). Some of the problems associated with their application are addressed to alteration in erythrocyte (ERY) rheology. OBJECTIVE: We intended to estimate in vitro and compare the aggregation power (AP) of these molecules related to ERY interactions. METHODS: Washed human ERY are used during the study. The zeta sedimentation technique is used to quantify the cell aggregation. Zeta sedimentation ratio (ZSR) based indices (AI) are calculated. The hydrodynamic …radius (Rh ) of the polymer molecules is determined using viscometry. RESULTS: For all polymers tested a linear range in the relationship AI – concentration was found. The slope of the calculated line was interpreted as measure of the molecule’s AP. The following ranking was obtained: PEG >PVP >DX >HES. Within the same chemical type of polymer, increasing Rh of the molecules leads to elevated AI. Comparison of the AP of molecules with similar Rh reveals a significant dependence on their chemical nature. CONCLUSIONS: Our results show that molecule’s AP is significantly dependent on their chemical nature – i.e. not only molecular size does matter. Show more

Keywords: Erythrocyte, aggregation, polymer, Zeta sedimentation ratio, hydrodynamic radius

DOI: 10.3233/CH-168019

Citation: Clinical Hemorheology and Microcirculation, vol. 64, no. 4, pp. 845-851, 2016

Authors: Lee, K. | Priezzhev, A. | Shin, S. | Yaya, F. | Meglinski, I.

Article Type: Research Article

Abstract: BACKGROUND: The novel measure of the red blood cells (RBC) aggregation (RBC-A) – the critical (minimum) shear stress (CSS) to prevent the cells from aggregation was found to be a promising clinically significant parameter. However, the absolute values of this parameter were found to change significantly depending on the shearing geometry (cup-and-bob, cone-plate or microchannel-flow) and have different temperature dependences along with it. The direct confirmation of these dependences aimed to find out the correct values is still pending. OBJECTIVE: In this work, we aim to assess the absolute values of CSS at different temperatures. METHODS: …The single cell level measurements of CSS were performed using optical tweezers. The measurements were carried out in heavily diluted suspensions of RBCs in plasma. RESULTS: The temperature dependent changes in CSS were measured at the points (22 and 38°C), in which the cup-and-bob and cone-plate systems yielded about 1.5-fold different values, while the microchannel-flow system yielded a constant value. The single cell CSS were found to be 362±157 mPa (22°C) and 312±57 mPa (38°C). CONCLUSIONS: Our results prove that the microfluidic-flow approach is reflecting the RBC-A correctly. While the CSS values measured with other systems show the temperature dependent effect of the shearing geometry. Show more

Keywords: Red blood cell, aggregation, critical shear stress, temperature, shearing-geometry, single-cell level measurements, optical tweezers, microfluidic flow

DOI: 10.3233/CH-168020

Citation: Clinical Hemorheology and Microcirculation, vol. 64, no. 4, pp. 853-857, 2016

Authors: Silva, Marisa | Vargas, Sofia | Coelho, Andreia | Dias, Alexandra | Ferreira, Teresa | Morais, Anabela | Maia, Raquel | Kjöllerström, Paula | Lavinha, João | Faustino, Paula

Article Type: Research Article

Abstract: Sickle cell anemia (SCA) is an autosomal recessive disease caused by the HBB:c.20A>T mutation that leads to hemoglobin S synthesis. The disease presents with high clinical heterogeneity characterized by chronic hemolysis, recurrent episodes of vaso-oclusion and infection. This work aimed to characterize by in silico studies some genetic modulators of severe hemolysis and stroke risk in children with SCA, and understand their consequences at the hemorheological level. Association studies were performed between hemolysis biomarkers as well as the degree of cerebral vasculopathy and the inheritance of several polymorphic regions in genes related with vascular cell adhesion and vascular …tonus in pediatric SCA patients. In silico tools (e.g. MatInspector ) were applied to investigate the main variant consequences. Variants in vascular adhesion molecule-1 (VCAM1 ) gene promoter and endothelial nitric oxide synthase (NOS3 ) gene were significantly associated with higher degree of hemolysis and stroke events. They potentially modify transcription factor binding sites (e.g. VCAM1 rs1409419_T allele may lead to an EVI1 gain) or disturb the corresponding protein structure/function. Our findings emphasize the relevance of genetic variation in modulating the disease severity due to their effect on gene expression or modification of protein biological activities related with sickled erythrocyte/endothelial interactions and consequent hemorheological abnormalities. Show more

Keywords: Sickle cell anemia, VCAM1, NOS3, genetic modulators, in silico analysis

DOI: 10.3233/CH-168048

Citation: Clinical Hemorheology and Microcirculation, vol. 64, no. 4, pp. 859-866, 2016

Authors: Krüger-Genge, A. | Fuhrmann, R. | Jung, F. | Franke, R.P.

Article Type: Research Article

Abstract: The endothelialization of cardiovascular prostheses is known to improve their haemocompatibility. As such body-foreign materials often do not endothelialize spontaneously. A lot of in vitro studies are ongoing how endothelialization of biomaterials can be improved. In this study the influence of different components of a tissue-typical extracellular matrix (ECM) like laminin, fibronectin or gelatin on the formation of an endothelial cell monolayer and on the shear resistance of adherent cells on these substrates was studied. The study revealed that the density of human venous endothelial cells (HUVEC) monolayers differed markedly between cells grown on a natural ECM and …cells grown on singularized components of an ECM (p  < 0.001). Only HUVEC grown on laminin showed similar densities and a stress fiber pattern comparable to HUVEC grown on the ECM. HUVEC grown on gelatin- or fibronectin-coated coverslips were less firmly attached to the substrate; frequently individual HUVEC and even groups of cells detached. Concluding it seems that coating of implants with laminin supports the formation of shear resistant endothelial cell (EC) monolayer - superior to other ECM components. Show more

Keywords: HUVEC, extracellular matrix, laminin, fibronectin, gelatin

DOI: 10.3233/CH-168051

Citation: Clinical Hemorheology and Microcirculation, vol. 64, no. 4, pp. 867-874, 2016

Authors: Rozanovic, Martin | Csontos, Csaba | Bogár, Lajos | Szélig, Lívia | Bocskai, Tímea | Kovács, Patrícia | Matancic, Marianna | Miseta, Attila | Loibl, Csaba

Article Type: Research Article

Abstract: BACKGROUND: In polytrauma and burn injury Systemic Inflammatory Response Syndrome (SIRS) develops. SIRS is presented in many hospitalized patients, including those who never develop infection or sepsis. Both in SIRS and sepsis the leukocyte activation occurs. In acute phase reaction leukocytes’ upward flotation i.e. leukocyte antisedimentation rate (LAR) can indicate infectious origin. OBJECTIVE: To evaluate the predictive power of LAR, serum C-reactive protein (CRP) and procalcitonin (PCT) levels regarding mortality risk and development of septic complications. METHODS: In a prospective, observational study, 36 patients were followed for 5 days (T1-T5) after admission to a critical …care unit immediately with severe polytrauma or burn injury. Eleven patients developed septic complications, their LAR, CRP and PCT levels were analyzed before and after 3 days of sepsis was declared. RESULTS: Ten patients died due to septic complications. In survivors LAR at T1 (p  < 0.001) and T2 (p  < 0.001) as well as CRP at T1 (p  < 0.05) were significantly higher compared to controls and non survivors. In septic patients LAR (p  < 0.05) and CRP (p  < 0.05) showed a significant drop one day before sepsis was declared. PCT levels failed to predict this. CONCLUSIONS: Drop in LAR and CRP levels may be warning signs regarding the onset of septic complications after severe polytrauma and burn injury. Show more

Keywords: Mechanical and heat trauma, inflammatory response, leukocyte antisedimentation rate, C-reactive protein, procalcitonin

DOI: 10.3233/CH-168024

Citation: Clinical Hemorheology and Microcirculation, vol. 64, no. 4, pp. 875-885, 2016