Hemorheology is the science of blood circulatory flow mechanics. It is important with respect to abnormal blood physiologic function, disease, premature fatigue or reduced performance following exposure to non-disease related stress such as exercise. Circulatory flow mechanics comprises a complex interaction of multiple pathways that can give rise to a hemorheologic abnormality such as an increase in a blood viscosity determinant, an increase in phosphatidlyserine exposure, or an increase in the expression of adhesion molecules on the surface of blood or endothelial cells.
Hemorheologic determinants (factors which influences circulatory flow mechanics) include a (1) blood viscosity determinant, (2) phosphatidylserine exposure and (2) expression of adhesion molecules on the surface of blood or endothelial cells. A hemorheologic abnormality refers to an abnormal level of a hemorheologic determinant in a subject. Hemorheologic abnormalities result in reduced blood flow, increased resistance to blood flow and tissue oxygen deficit in the systemic system or hypertension in the pulmonary system leading to systemic or pulmonary pathology or pathophysiology or premature fatigue or reduced performance.
(1) a blood viscocity determinant is a conventional term used by hemorheologists to refer to factors which, if altered, can increase blood viscosity to abnormal levels. The most common blood viscosity determinants include (a) red blood cell concentration, (b) red blood cell aggregation, (c) red blood cell rigidity (resulting in reduced deformability), (d) plasma viscosity, and (e) abnormal red blood cell shape (e.g., formation of echinocytes, stomatocytes or elliptocytes).
(a) Hematocrit (Hct) is the prime determinant of blood viscosity. The more cells, the greater the viscosity. Unlike that of exercising humans, the Hct of exercising horses increases to polycythemic levels. This is because unlike the human spleen, the equine spleen sequesters nearly half the total erythrocyte mass. Upon exercise, it mobilizes the sequestered erythrocytes into the circulation which increases blood viscosity.
(b) blood changes its configuration as it flows in the circulation; particles in the central axis of vessels travel fastest. Shear rate (proportional to velocity of flow) differs throughout the circulation depending upon the vessel diameter and blood flow velocity.
(c) Deformability lowers blood viscosity and provides erythrocytes with a property that allows them to pass through channels much smaller than their own diameter. On the other hand, increased reigidity reduces the ability of the cell to bend its membrane, causing the red blood cell to lose its biconcave shape and preventing the red blood cell from deforming.
(d) The only constituents of plasma that have an effect on blood viscosity are fibrinogen and macromolecular globulines (e.g., IgG, IgA and IgM).
(e) Echinocytes are rigid cells due to a decreased surface area-to-volume ratio which occurs because the tips of spicules bud off and reduce their surface area. Their rigidity causes an impeded blood flow and reduces tissue oxygenation in much the same way as do sickle cells. Another examples of an abnormally shaped red blood cell is the stomatocyte characterized by a pale, elongated, mouth-like area in the center of the cells. Another abnormally shaped red blood cell is the elliptocytes or ovalocytes which appear oval or elongated in shape and are rich in hemoglobin.
(2) Phosphatidylserine Exposure: Membranes of normal erythrocytes contain 4 major phospholipid classes districtued asymmetrically between lipid bilayers; Phosphatidylcholine (PC) and sphingomyelin (SM) localize mainly in the outer bilayer. Phosphatidylethanolamine (PE), however, resides mainly in the inner bilayer, while phosphatidylserine (PS) resides exclusively there. Normal biconcave erythrocytes transform into echinocytes after a membrane perturbation induces phospholipid redistribution and causes PS expression on the cell’s surface.
(3) adhesion molecules: blood cells (RBCs, platelets, leukocytes), endothelial cells and plasma contain adhesion molecules which, when stimulated, interact with their individual specific receptors and reversibly bind cells-to-cells, cells-to-protein, and protein-to protein. With respect to the cell adhesion type (blood cells-to-blood cells, for example), adhesion molecules include an immunoglobulin (e.g., IgG, IgA, IgM), a thrombospondin protin, a fibronectin protein etc). With respect to blood cells-to-endothelial cells, adhesion molecules include I-CMA-1, an integrin protein, a selectin protein, a cadherin protein a cluster of differentiation (CD35, CD36), etc.
The term hemorheologically-active compound refers to a compound that improves blood flow by reducing an abnormal level of a hemorheological determinant.