Nadia Antonova

Erythrocyte aggregation at non-steady flow conditions: A comparison of characteristics measured with electrorheology and image analysis

In the present study electro-rheology (Contraves LS30 viscometer-based system) and optical shearing microscopy (Lincam CSS450 system and image analysis) techniques have been utilized in order to provide quantitative data on the behaviour of the microstructural properties of whole normal human blood at non-steady flow conditions. The objective of this work is to contribute towards a better understanding of red blood cell aggregation at flow conditions similar to that occurring in a circulatory system and to aid the interpretation and validation of electro-rheological data through a quantitative comparison with data acquired with optical shearing microscopy. Electro-rheology is a promising technique that has been used to provide bulk fluid properties, showing potential for basic research and diagnostic purposes, whereas optical shearing techniques offer a direct assessment of blood microstructure at a cellular level. However, little information exists in the literature regarding the relationships between electro-rheological measurements and blood microstructural characteristics. The results showed that the different non-steady flow conditions affect differently the dynamics of aggregation varying from a parabolic-decrease to an inverted S-shape curve with time. For a wide range of the non-steady flows results obtained with the two different techniques agree to a difference between 1.2 and 12%.

Platelet morphological, functional and rheological properties attributable to addictions.

Hemorheological abnormalities such as elevated whole blood viscosity, plasma viscosity, erythrocyte deformability and platelet aggregation, hematocrit and fibrinogen levels, are frequently examined as diagnostic tool and prognostic relevance in socially important hemorheological disorders. Distinct biological - morphological and functional platelet alterations, have been described in different addictions (heroin-, cocaine-, nicotine-, alcohol-, etc.). Chronic addictions could cause biochemical and conformational changes in platelets and their membranes, thus modulating platelet receptor expression, morphology (anisocytosis, giant platelets) and activation (alpha-granule release), platelet aggregation and hemorheological properties. Some of these alterations in chronic addicts - documented at cellular- and molecular level, could be easily used as a precise diagnostic tool with regard to thromboembolic complications and microcirulation injuries attributable to addictions. The present review focuses on some changes in platelet morphological, functional and rheological properties induced by chronic opiate/opioid abuse. Hypothesis is accumulated that free fatty acids (FFAs) and especially oleic acid (OA) could cause positive molecular and conformational changes in platelets of addicts with hemorheological disorders.

Hemorheology and heart rate variability in patients with diabetes mellitus type 2

Our study aimed to investigate the relationship between hemorheological parameters and heart rate variability (HRV) in patients with diabetes mellitus type 2. Hemorheological variables, including hematocrit (Ht), fibrinogen (Fib), whole blood (WBV) and plasma viscosity (PV) at shear rates of 0.0237 s(-1) to 128.5 s(-1) were examined in 20 patients with diabetes mellitus type 2 and in 10 control subjects. They all underwent non-invasive short-term monitoring of heart rate at rest and after passive head-up tilt. Measurement of the R-R intervals and calculation of the time domain parameters and the power spectral data were performed by our softwear, using fast Fourier transformation. Significant increase of Fib and WBV in the patients in comparison to controls was found within the range of shear rates 0.0237 s(-1) to 128.5 s(-1). In the diabetic patients parallel decrease of the total power (TP), the low frequency spectral power (LF) and of the mean RR and mild increase of the low frequency-high frequency ratio (LF/HF) at rest were established. This tendency was kept after the passive tilt. In patients with diabetes mellitus type 2 the increased blood viscosity was associated with reduced HRV.

Hemorheology and vascular reactivity in patients with diabetes mellitus type 2.

The study aimed to investigate the hemorheological parameters in patients with diabetes mellitus type 2 and to estimate their relationship with the cerebral and cutaneous blood flow and their responses to postural changes. The basic hemorheological constituents: hematocrit (Ht), fibrinogen (Fib), whole blood (WBV) and plasma viscosity (PV) were examined in 20 patients with diabetes mellitus type 2 and in 10 healthy age and sex matched controls. Blood flow velocity in the middle cerebral artery (MCA) was measured by transcranial Doppler monitoring at rest and during 5-min head-up tilt. Also laser Doppler-recorded tiptoe skin blood flow was investigated and venoarteriolar reflex perfusion responses to postural impact was monitored. Significant increase of Fib and WBV at shear rates of 0.0237 s(-1) to 128.5 s(-1) in the patients in comparison to controls was found. The postural challenge caused decrease of the cerebral blood flow velocity and increase of the resistance index (RI) in the diabetic patients. The initial mean skin perfusion values of the tiptoes and the venoarteriolar constriction response indices were significantly higher in the diabetes group. In the patients with diabetes mellitus type 2 the increased blood viscosity values were associated with impaired cerebrovascular and peripheral vascular responces.

Experimental evaluation of mechanical and electrical properties of RBC suspensions under flow. Role of RBC aggregating agent

Mechanical and electrical properties of red blood cells (RBC) suspensions in dextran 70 (Dx70), dextran 150 (Dx150), dextran 500 (Dx500) and polyethileneglycol (PEG) 35,000 with different concentrations were evaluated through apparent viscosity and conductivity measurements under steady and unsteady flow conditions. RBCs suspensions of the washed RBS in PBS (control) and Dx70, Dx150, Dx500 and PEG in PBS with different concentrations, adjusted to the same hematocrit of 40% were used for the experiments. Conductivity time and shear rate dependences in parallel with the rheological properties of the samples were studied under transient flow regimes at different local structure of the uniform Couette flow. Their relationships on dextrans and PEG concentrations were evaluated too. Low shear viscosity increased and conductivity decreased of RBC suspensions, compared to non-aggregating suspensions, depending on dextrans and PEG concentrations. A time course of blood conductivity recorded under different flow conditions provides experimental description of RBC aggregation-disaggregation processes and other cell-cell interactions. The results show that the blood conductivity is strongly dependent on the considered blood factors and is influenced by flow, shear rates and concentration of dextran and PEG solutions.

STENOSIS EFFECTS ON THE FLUID MECHANICS OF THE COMMON CAROTID ARTERY BIFURCATION FOR UNSTEADY FLOWS

The time-varying blood flow in the common carotid artery (CCA) bifurcation is numerically studied on the basis of Navier-Stokes equations for four different cases, including cases with stenoses at different sites in the vicinity of the bifurcation. The cases studied were: (a) without stenoses, (b) with one stenosis upstream the bifurcation, (c) with two opposite stenoses upstream the bifurcation and (d) with an additional stenosis on the apex of the bifurcation. The mesh was generated via a geometry reconstruction and imported into a computational fluid dynamics (CFD) solver. The numerical results of the blood flow in the CCA bifurcation gave a detailed picture of the axial velocity and presented as velocity and vorticity magnitudes. More specifically, it was observed that the appearance of stenotic regions upstream the bifurcation affect both the velocity and vorticity characteristics, whereas a stenoses on the apex of the bifurcation seems to have a small effect on the vorticity characteristics downstream the flow.

Hematological changes in case of chronic cadmium intoxication and monensin detoxication. Relationship with rheological variables

The study evaluated the affect of chronic cadmium (Cd) and monensin treatment on some hematological parameters and its relationship with the rheological variables. Adult male mice were subjected to chronic treatment with cadmium acetate [Cd(CH3COO)2 × 2H2O] (group 1), Cd(CH3COO)2 × 2H2O followed by treatment with low dose monensin (group 2) and Cd(CH3COO)2 × 2H2O followed by high dose monensin treatment (group 3). Cd(CH3COO)2 × 2H2O and deprotonated monensin were dissolved in distilled water and given daily to the experimental animals. Mice drinking distilled water served as a control group (group 4). Hematological parameters and erythrocyte morphology were evaluated in parallel with whole blood viscosity (WBV). Cd treatment reduced Hb and increased RDW. The addition of high dose monensin significantly improved erythrocytic indices compared to the control. Erythrocyte anisocytosis was observed in blood smears of Cd-treated mice corresponding to the increased RDW. WBV was significantly elevated in the experimental groups in the whole range of shear rates compared to the control group and in groups 2 and 3 was lower than in group 1 but remained higher compared to group 4. Correlations were found between WBV and RBC, Hb, Hct, MCV and RDW. The results suggest that hemorheological parameters such as WBV should be monitored in parallel with the hematological parameters when monensin is applied and heavy metal intoxication is suspected.

Influence of hemorheological parameters and mean blood pressure on carotid blood flow asymmetry in patients with chronic unilateral cerebral infarctions.

The study aimed to follow the influence of some hemorheological parameters and mean blood pressure (MBP) on the carotid blood flow asymmetry in 20 patients with chronic unilateral cerebral infarctions (UCI) as compared to 30 patients with transient ischemic attacks (TIAs), 17 patients with risk factors (RF) for cerebrovascular disease (CVD) and 11 healthy controls. Hemorheological variables: hematocrit (HT), plasma (PV) and whole blood viscosity (WBV), serum lipids and echocardiographic parameters were investigated. Blood pressure (systolic, diastolic and mean) was registered and color duplex sonography of the carotid arteries was performed. The lumen diameter, the intima media thickness (IMT) and the blood flow velocity (systolic, mean and diastolic) in the carotid arteries were examined and the velocity asymmetry ratio (AR) was calculated. Significant increase of HT in UCI, of mean blood pressure (MBP) in the patients with RF and TIAs and of IMT and velocity parameters in all patients was established. The correlation analysis revealed parallel influence of HT, MBP, cardiac function, IMT, lumen diameter and some of the modifiable RF on the carotid AR in patients with chronic UCI affecting mainly the collateral circulation. The complex investigation of these factors would enable us to individualize the therapeutic approach in the patients with cerebral ischemic events.

Microvascular reactivity to thermal stimulation in patients with diabetes mellitus and polyneuropathy

The study aimed to investigate local thermally induced microvascular reactivity in patients with type 1 (T1DM) or type 2 diabetes mellitus (T2DM) and polyneuropathy and to compare it with healthy controls. A hundred and fourteen subjects were investigated divided into 3 groups: 1st group -20 patients with T1DM; 2nd group -50 patients with T2DM; 3rd group -44 healthy controls. The skin perfusions of the first tiptoe were monitored by laser Doppler flowmetry during thermal test. The initial (PUi) and basal perfusions at 32°C (PUb) tended to be higher in the DM groups and the PUb of T1DM group was higher compared with the healthy subjects. The perfusion responses to heating were attenuated in the patients compared with the controls. The calculated vasodilator heat-induced indices were significantly lower and the vasoconstrictor indices during relative cooling in the recovery period were significantly higher in DM patients related to the healthy subjects. The reduced cutaneous microvascular responses to local thermal stimulation in the plantar sides of the toes of both T1DM and T2DM patients with polyneuropathy were similar to those found by previous studies in other investigated sites of glabrous and nonglabrous skin of patients with DM.

Methods in hemorheology and their clinical applications1

The lecture was presented during the Fåhraeus award ceremony for 2016 at the University of Lisbon. It summarizes the main results and some of the more important hemorheological contributions achieved in the Laboratory of Biodynamics and Biorheology of the Institute of Mechanics to BAS and in collaboration with other laboratories of the research group, involved in many studies explaining hemorheological disturbances in various clinical conditions. An original method for the study of microstructural changes in the biological fluids by measuring the electrical conductivity simultaneously with the the rheological properties of red blood cells (RBC) in the whole blood and red blood cell suspensions in a viscometric flow was suggested. The influence of the disturbed hemorheological parameters on the common carotid artery and cerebral blood flow was studied. Analysis of blood flow in the common carotid artery bifurcation with stenosis was done. This lecture does not claim to be a comprehensive review, and many important studies were not cited. The author would like to acknowledge the valuable collaboration of all those cited in the reference list.