Blood is a two-phase suspension of formed elements (i.e., red blood cells [RBCs], white blood cells [WBCs], platelets) suspended in an aqueous solution of organic molecules, proteins, and salts called plasma. The apparent viscosity of blood depends on the existing shear forces (i.e., blood behaves as a non-Newtonian fluid) and is determined by hematocrit, plasma viscosity, RBC aggregation, and the mechanical properties of RBCs. RBCs are highly deformable, and this physical property significantly contributes to aiding blood flow both under bulk flow conditions and in the microcirculation. The tendency of RBCs to undergo reversible aggregation is an important determinant of apparent viscosity because the size of RBC aggregates is inversely proportional to the magnitude of shear forces; the aggregates are dispersed with increasing shear forces, then reform under low-flow or static conditions. RBC aggregation also affects the in vivo fluidity of blood, especially in the low-shear regions of the circulatory system. Blood rheology has been reported to be altered in various physiopathological processes: (1) Alterations of hematocrit significantly contribute to hemorheological variations in diseases and in certain extreme physiological conditions; (2) RBC deformability is sensitive to local and general homeostasis, with RBC deformability affected by alterations of the properties and associations of membrane skeletal proteins, the ratio of RBC membrane surface area to cell volume, cell morphology, and cytoplasmic viscosity. Such alterations may result from genetic disorders or may be induced by such factors as abnormal local tissue metabolism, oxidant stress, and activated leukocytes; and (3) RBC aggregation is mainly determined by plasma protein composition and surface properties of RBCs, with increased plasma concentrations of acute phase reactants in inflammatory disorders a common cause of increased RBC aggregation. In addition, RBC aggregation tendency can be modified by alterations of RBC surface properties because of RBC in vivo aging, oxygen-free radicals, or proteolytic enzymes. Impairment of blood fluidity may significantly affect tissue perfusion and result in functional deteriorations, especially if disease processes also disturb vascular properties.

http://health120years.com/cn/pdf/hd_Nobel_1920_HD_Blood.pdf

Blood rheology and hemodynamics.

http://burstscience.com/pdfs/roleantioxhealth.pdf

Antioxidants: what role do they play in physical activity and health?

The fluorescence intensity and lifetime of the 4,4'-difluoro-4-bora-5-(p-oxoalkyl)phenyl-3a,4a-diaza-s-indacene (1) show a strong correlation with the viscosity of the medium due to the viscosity-dependent twisting of the 5-phenyl group, which gives access to the dark nonemissive excited state. We propose a sensitive and versatile method for measuring the local microviscosity in biological systems, based on the determination of the fluorescence lifetime of 1. Fluorescence lifetime imaging (FLIM) performed on live cells incubated with 1 demonstrates the distinct intracellular lifetime of the molecular rotor of 1.6 +/- 0.2 ns corresponding to the intracellular viscosity of ca. 140 cP. Time-resolved fluorescence anisotropy of 1 in cells confirms insignificant binding of the fluorophore. The viscosity value obtained in the present study is considerably higher than that of water and of cellular cytoplasm. The high viscosity of intracellular compartments is likely to play an important role in vital intracellular processes, including the rate of diffusion of reactive oxygen species, causing programmed cell destruction.

/pdf/molecular-rotor-measures-viscosity-of-live-cells-via-172fswp5ay.pdf

Molecular Rotor Measures Viscosity of Live Cells via Fluorescence Lifetime Imaging

Recent studies have underscored questions about the balance of risk and benefit of RBC transfusion. A better understanding of the nature and timing of molecular and functional changes in stored RBCs may provide strategies to improve the balance of benefit and risk of RBC transfusion. We analyzed changes occurring during RBC storage focusing on RBC deformability, RBC-dependent vasoregulatory function, and S-nitrosohemoglobin (SNO-Hb), through which hemoglobin (Hb) O(2) desaturation is coupled to regional increases in blood flow in vivo (hypoxic vasodilation). Five hundred ml of blood from each of 15 healthy volunteers was processed into leukofiltered, additive solution 3-exposed RBCs and stored at 1-6 degrees C according to AABB standards. Blood was subjected to 26 assays at 0, 3, 8, 24 and 96 h, and at 1, 2, 3, 4, and 6 weeks. RBC SNO-Hb decreased rapidly (1.2 x 10(-4) at 3 h vs. 6.5 x 10(-4) (fresh) mol S-nitrosothiol (SNO)/mol Hb tetramer (P = 0.032, mercuric-displaced photolysis-chemiluminescence assay), and remained low over the 42-day period. The decline was corroborated by using the carbon monoxide-saturated copper-cysteine assay [3.0 x 10(-5) at 3 h vs. 9.0 x 10(-5) (fresh) mol SNO/mol Hb]. In parallel, vasodilation by stored RBCs was significantly depressed. RBC deformability assayed at a physiological shear stress decreased gradually over the 42-day period (P < 0.001). Time courses vary for several storage-induced defects that might account for recent observations linking blood transfusion with adverse outcomes. Of clinical concern is that SNO levels, and their physiological correlate, RBC-dependent vasodilation, become depressed soon after collection, suggesting that even "fresh" blood may have developed adverse biological characteristics.

https://www.pnas.org/content/pnas/104/43/17063.full.pdf

Evolution of adverse changes in stored RBCs.

Oxidative stress in malaria parasite-infected erythrocytes: Host-parasite interactions

This document, supported by both the International Society for Clinical Hemorheology and the European Society for Clinical Hemorheology and Microcirculation, proposes new guidelines for hemorheolog ...

/pdf/new-guidelines-for-hemorheological-laboratory-techniques-csd2ii48oa.pdf

New guidelines for hemorheological laboratory techniques

The Laser-assisted Optical Rotational Cell Analyzer (LORCA) is unique in its capacity to measure at least two important hemorheological parameters, i.e., deformability of red blood cells (RBC) as well as their aggregation behaviour. In this communication the main principles and characteristics of the aggregometer mode of this instrument are described. Via syllectometry (i.e., laser backscatter versus time), the method allows the measure of both static and kinetic parameters of the aggregation process, e.g., total extent of aggregation, aggregation half time and a combination of these, defined as aggregation index. When the syllectogram deviates from that representing normal rouleaux formation, e.g., in the case of RBC clump formation, this is signalled by a fit error. Maximal flexibility is obtained by various options like an automated re-iteration procedure (which enables to measure the aggregation tendency and/or the aggregate stability) and aggregation at low shear rate. Experiments dealing with reproducibility, stability and sensitivity of the instrument are described. The latter include a few "classic" methods for inducing subtle changes in RBC aggregation behaviour both regarding cellular factors (heat treatment) and changes in medium constituents (fibrinogen, dextrans).It can be concluded that the aggregometer mode of the LORCA considerably increases the feasibility of this instrument for hemorheological investigations.

The Laser-assisted Optical Rotational Cell Analyzer (LORCA) as red blood cell aggregometer

The capacity of red blood cells to deform is of crucial importance for both macro and microcirculation. A satisfying technique for the measurement of this parameter is lacking so far. We have developed and tested in various studies an instrument for automatic measurement of red cell deformability by laser diffractometry. Recently, it appeared that the applicability of the instrument could be extended for measuring another structural hemorheological parameter, red blood cell aggregation. In this communication, a description of the Laser­ assisted Optical Rotational Cell Analyser (LORCA) is followed by the general methodology for the measurement of both red blood cell deform ability and aggregation, demonstrating the practical versatility ofthis instrument in the field of hemorheology.

Laser-assisted optical rotational cell analyser (L.O.R.C.A.); I. A new instrument for measurement of various structural hemorheological parameters

This publication primarily focuses on the macro- and micro-rheological behavior of blood and its formed elements, on interactions between the formed elements and blood vessel walls, and on the microvascular aspects of hemodynamics. Since many aspects of hemorheology and hemodynamics are affected by disease or clinical states, these effects are discussed here, such as hyperviscosity syndromes, therapy for disturbed blood rheology, and methods in hemorheology and hemodynamics. Sections of the handbook include History of Hemorheology; Hemorheology, covering basic aspects, blood composition, blood rheology, cell mechanics, pathophysiology, methods and comparative studies; Hemodynamics, covering basic principles, microcirculation, in vivo effects, endothelium and methods; and clinical aspects of Hemorheology, covering hyperviscosity, clinical significance and treatment.The goal is to foster greater interchange between workers in the field so as to promote collaborative efforts and, hopefully, improved health. In selecting topics for this handbook the editors have attempted to provide a general overview of both basic science and clinical hemorheology and hemodynamics. Hemorheology and hemodynamics are closely related, the former dealing with all aspects of the flow and interactions of the individual blood cells mostly dealing with all aspects of the flow and interactions of the individual blood cells mostly studied in vitro, the latter with the in vivo relationships among vessel architecture, driving pressure, flow rate and shear stress. The linkage between the in vitro and in vivo research described in the book will be of interest to both basic science and clinical investigators.

Handbook of hemorheology and hemodynamics

Decreased erythropoiesis and increased clearance of both parasitized and noninfected erythrocytes both contribute to the pathogenesis of anemia in falciparum malaria. Erythrocytes with reduced deformability are more likely to be cleared from the circulation by the spleen, a process that is augmented in acute malaria. Using a laser diffraction technique, we measured red blood cell (RBC) deformability over a range of shear stresses and related this to the severity of anemia in 36 adults with severe falciparum malaria. The RBC deformability at a high shear stress of 30 Pa, similar to that encountered in the splenic sinusoids, showed a significant positive correlation with the nadir in hemoglobin concentration during hospitalization (r = 0.49, P < 0.002). Exclusion of five patients with microcytic anemia strengthened this relationship (r = 0.64, P < 0.001). Reduction in RBC deformability resulted mainly from changes in unparasitized erythrocytes. Reduced deformability of uninfected erythrocytes at high shear stresses and subsequent splenic removal of these cells may be an important contributor to the anemia of severe malaria.

Max R. Hardeman

Papers

New guidelines for hemorheological laboratory techniques

The Laser-assisted Optical Rotational Cell Analyzer (LORCA) as red blood cell aggregometer

Laser-assisted optical rotational cell analyser (L.O.R.C.A.); I. A new instrument for measurement of various structural hemorheological parameters

Handbook of hemorheology and hemodynamics

Red blood cell deformability as a predictor of anemia in severe falciparum malaria.