Clinical Hemorheology and Microcirculation

Gender, menstrual cycle and oral contraceptives may have influence on mechanical properties of Red Blood Cell (RBC) and particularly on RBC deformability. So cell transit parameters have been assessed by filtration with the Cell Transit Analyser (CTA) for a large healthy adult population (seventy‐nine males and one‐hundred‐fifteen females). The CTA provides the distribution of cell transit times of 5000 red blood cells, the mean transit time of the population and different percentiles such as p50, p75, p90 and p95. No effect of oral contraceptives was found. Nevertheless, influence of sex and menstrual cycle were demonstrated. A significant increase of the filtration parameters measured in the female population with respect to the male population and during menstruation, preovulation and post‐ovulation periods was observed. During ovulation, the CTA parameters are comparable to the same parameters found in males.

The life‐extending effects of regular exercise are related to a decrease in both coronary and peripheral vascular morbidity, associated with some improvements in cardiovascular risk factors. A possible link between the beneficial metabolic and hemodynamic effects of exercise could be blood rheology, which is markedly affected by exercise. We propose here a description of the hemorheological effects of exercise as a triphasic phenomenon. Short‐term effects of exercise are an increase in blood viscosity resulting from both fluid shifts and alterations of erythrocyte rheologic properties (rigidity and aggregability). Increased blood lactate, stress, and acute phase play a role in this process. Middle‐term effects of regular exercise are a reversal of these acute effects with an increase in blood fluidity, explained by plasma volume expansion (autohemodilution) that lowers both plasma viscosity and hematocrit. Long‐term effects further improve blood fluidity, parallel with the classical training‐induced hormonal and metabolic alterations. While body composition, blood lipid pattern, and fibrinogen improve (thus decreasing plasma viscosity), erythrocyte metabolic and rheologic properties are modified, with a reduction in aggregability and rigidity. On the whole, these improvements reflect a reversal of the so‐called “insulin‐resistance syndrome” induced by a sedentary lifestyle. Since impaired blood rheology has been demonstrated to be at risk for vascular diseases, the hemorheologic effects of exercise can be hypothesized to be a mechanism (or at least a marker) of risk reversal. This latter point requires further investigation. The physiological meaning of the triphasic pattern of exercise‐induced alterations of blood rheology is uncompletely understood, but increased blood fluidity may improve several steps of oxygen transfer to muscle, as clearly demonstrated in hypoxic conditions. Increasing evidence emerges from the literature, that blood fluidity is a physiological determinant of fitness.

The present study has been designed to examine the role of a hyperglycaemic spike of short duration as a factor possibly involved in haemorheological microcirculatory and (or) haemostatic dysfunctions in ten insulin‐dependent diabetes mellitus patients (IDDM) and five healthy volunteers. The hyperglycaemic spike was induced by glucose infusion via GCIIS Biostator. Blood viscosity, erythrocyte aggregation, erythrocyte deformability, plasma viscosity and proteins’ levels, cell counts, and transcutaneous oxygen pressure were investigated during normoglycaemic period and at the end of a 1 h hyperglycaemic spike. Hyperglycaemia induced in IDDM patients significant decreases in erythrocyte aggregation, in blood and plasma viscosities and in both fibrinogen and albumin levels. The number of platelets was significantly decreased as a result of the hyperglycaemic spike. There was no significant change induced by the hyperglycaemic spike in healthy volunteers. These findings show that a hyperglycaemic spike of 280 mg/dl (15.6 mmol/l) of short duration in IDDM patients causes numerous significant changes in both blood components and rheological behaviour. These changes were accompanied by a significant decrease in transcutaneous oxygen tension indicating an impaired tissue oxygenation during the hyperglycaemia.

A modified Casson equation was established, verified satisficatorily for real conditions and suggested for use in clinical hemorheology. It provides 5 Casson parameters, i.e., Casson yield stress, Casson viscosity, the first critical point of shear rate to cause rouleaux to be broken down into smaller units, the second critical point of shear rate to completely disaggregate into individual erythrocytes, the difference between the two critical points, and also gives two series of the 5 above‐mentioned Casson parameters, respectively, under original hematocrit and the standardized hematocrit of 45%. This equation not only reveals the apparent abnormalities of hypertensive patients and normalities of the healthy persons, but also reveals hidden abnormalities for patients with either low or high hematocrit. For 20 cases of hypertensive patients with low hematocrit, the 5 Casson parameters have lower values than control, but the modified equation reveals their hidden higher values than control when their hematocrit is standardized to 45%. For 7 cases of polycythemia complicated with hypertension, the 5 Casson parameters are higher at their original hematocrit, and the modified equation reveals the higher parameters than control also when the hematocrit is standardized to 45%. For 8 cases of polycythemia without complications, the 5 Casson parameters are higher at their original hematocrit than control, while the modified equation still reveals their normalities when standardizing their hematocrit to 45%.

Many forms of tissue injury, whether due to physical or infectious sources, lead to the inflammatory response. During its course a wide variety of events takes place, including alterations in vascular contraction, in vascular permeability, in leucocyte activity and the initiation of the acute phase response. The last results in a leucocytosis and changes in the concentrations of a number of plasma proteins, including fibrinogen. They all cause alterations in haemodynamics, due in part to alteration in geometric resistance, but also to alterations in viscometric resistance as a result of changes in the haemorheological properties of the blood components locally and systemically. While some of these inflammation‐induced changes are useful on a local level and assist in the resolution of the damaging factor and in tissue repair, the systemic haemorheological effects may lead to deleterious haemodynamics. Many of the effects are well documented but two new possibilities arise. One is the potential effects of fibrinogen heterogeneity on blood rheology, and the other the possible effects of leucocyte protease release on the aggregability of the red cell.

In order to ascertain whether hemorheological alterations precede the atherosclerotic lesion in familial hypercholesterolemia (FH), we studied the lipid and hemorheological profile of 29 heterozygous FH children (12 males and 17 females), aged 12 {}\pm{} 3 years, and a well‐matched control group (CG), and assessed their plasma thrombomodulin level as an early marker of endothelial injury. No differences were found between FH children’s plasma thrombomodulin values (31.7 {}\pm{} 11.2 ng/ml) and those of the CG (27.8 {}\pm{} 15 ng/ml). However, the rheological variables of FH children and the CG were statistically different ( p<0.001 ) for fibrinogen (Fbg): 266 {}\pm{} 48 mg/dl vs. 205 {}\pm{} 32 mg/dl; erythrocyte aggregation at stasis (EAM _{0} ): 4.6 {}\pm{} 1.2 vs. 3.3 {}\pm{} 0.9; erythrocyte aggregation at low shear (EAM _{1} ): 7.9 {}\pm{} 1.7 vs. 6.1 {}\pm{} 0.8; and plasma viscosity (PV): 1.18 {}\pm{} 0.03 cP vs. 1.12 {}\pm{} 0.04 cP. Correlations between rheological parameters and lipids were found. The normal values obtained in FH children for plasma thrombomodulin suggest that the hemorheological alterations appear prior to the vascular injury, are in part related to dyslipemia and could contribute to the development of the atherosclerotic process by modifyng blood flow conditions.

In order to determine early changes in microcirculation and hemorheological parameters in diabetics, a cross‐sectional study was carried out with 273 children with diabetes mellitus type I during their vacation in a state country convalescent home for diabetic children and teenagers in Kaiserslautern. Compared to healthy children, typical changes of hemorheological variables as well as in the microcirculation of the skin and retina are observed in poorly controlled diabetic children. Morphological changes are obvious in capillary areas in form of marked capillary contortions and dilatations of venous branches, rigid erythrocytes, and hyperaggregable thrombocytes. An effort should be undertaken to normalize the pathologically changed parameters of blood fluidity and the microcirculation by an adequate control of blood glucose, and possibly by changes in dietary habits.

Molecular rotors, which structure can be 4‐(N,N‐dimethylamino)‐benzene, ‐benzylidene and ‐cinnamylidene derivatives and, also, coumarine‐like compounds, have photophysical characteristics which strongly depend on the environmental parameters (polarity, viscosity, temperature, etc.).

In this paper, a basic knowledge on molecular fluorescent rotors will be reminded and two fields of applications using molecular fluorescent rotors as optical sensors will be described: firstly, in polymer and, more particularly to detect the formation of hydrophobic microdomains, in the case of the aggregation of amphiphilic polymers (as models for globular proteins and/or enzymes) and, secondly, in cell biology, especially in liposomes (as models for biological membranes) to follow their thermotropic behavior and in endothelial cells under 3D fluorescence microscopy.

A simple and reproducible ‘syringe viscometer’ method was used to determine plasma viscosity, an important haemorheological parameter, in 27 (14 M, 13 F) nephrotic Nigerian patients. The plasma fibrinogen (PFC) and immunoglobulin levels (IgG, IgM, IgA) were also determined in these patients. Similar determinations were carried out in 30 (15 M, 15 F) age‐ and sex‐matched healthy control subjects for comparison.

The nephrotic patients had significantly higher relative plasma viscosity (RPV), PFC and IgM levels ( 2.02\pm 0.17 vs. 1.66\pm 0.19 , 6.48\pm 2.59 vs. 2.26\pm 0.91 g/l; 316.2\pm 169.0 vs. 186.0\pm 59.5 IU/ml, p<0.001 , respectively). However, IgG and IgA levels were significantly less ( 151.1\pm 88.7 vs. 205.7\pm 77.6 IU/ml, p<0.05 , and 95.8\pm 41.5 vs. 127.3\pm 31.3 IU/ml, p<0.01 , respectively).

In the nephrotic patients, plasma fibrinogen and IgM levels had a significant positive correlation with RPV ( r=0.444 , p<0.05 , and r=0.452 , p<0.02 , respectively).

The observed increased plasma viscosity in our nephrotic patients could on the long term predispose them to increased risk for cardiovascular morbidity.