Hemorheological changes in microcirculation: their mechanism and measurement technique.

Blood fluidity in the capillaries is affected significantly in diseases such as cardiac and brain infarcts, diabetic gangrene and many others. In view of the importance of physiology and pathology of capillary circulation, the hemorheological characteristics of the capillary blood flow are discussed in this article. Also, a new diagnosing technique for blood fluidity disorders is proposed. A computerized system for image analysis and determining blood rheological disorders for clinical and experimental use has also been discussed.

Hemorheological disorders in the microcirculation during septic shock in rats.

OBJECTIVES: The aim of the present study was the experimental analysis of blood rheological disorders in the microcirculation during endotoxic shock. METHODS: Experiments were carried out on 30 white laboratory rats of both sexes weighing about 200 g. The experimental animals were divided in two groups: the control group and the group undergoing experimental endotoxic shock. The following specific hemorheological properties were investigated in all animals during the experiments: red blood cells (RBC) aggregability, their deformability and the systemic hematocrit. RESULTS: We found that all the investigated hemorheological parameters appreciably changed underconditions of endotoxic shock. The RBC aggregability index was increased by a mean of 136%. As to the RBC deformability index was found to be decreased by 71%, and the systemic hematocrit lowered by 31%, as compared to the same parameters in the control group. CONCLUSION: The data obtained provide us with evidence that the hemorheological derangements associated with the development of the heavy microcirculatory disorders during endotoxic shock, are most significant factors.

Hemorheological disorders during ischemic brain infarcts in patients with and without diabetes mellitus.

The aim of the present study was the comparative analysis of the role of specific hemorheological derangements in the pathogenesis of ischemic brain infarcts with and without diabetes mellitus. Blood plasma viscosity, as well as red blood cells (RBC) aggregability were quantitatively investigated in all patients during the study. Both of the above mentioned indices of hemorheological disorders were significantly higher in the patients with brain infarcts and diabetes mellitus as compared to the control and the group of ischemic brain infarcts without diabetes. During the ischemic stroke, blood plasma viscosity was increased by a mean of 9.2 per cent in the first and by a mean of 17.6 per cent in the second group of patients. As to the erythrocyte aggregability index, it was changed considerably more - by a mean of 113.8 per cent during stroke without diabetes, while in the diabetic patients the RBC aggregability index was found to be increased by a mean of 147.3 per cent. Ischemic brain infarcts in patients with diabetes mellitus were associated with a significant increase of the patients' blood rheological disorders in all the investigated cases.

Hemorheological disorders in patients with type 1 or 2 diabetes mellitus and foot gangrene.

The aim of the present study was to evaluate blood rheological disorders, in particular RBC enhanced aggregation, and compare changes in these parameters in patients with type 1 and 2 diabetes mellitus. For evaluation of RBC aggregability in the present study we applied the "Georgian technique", which was developed and applied for several years in our laboratory. Its advantage is that it is a direct and quantitative method. In all the investigated patients, diabetes mellitus was complicated with the foot gangrenes. The patients were divided into two groups: (a) with type 1 and (b) with type 2 diabetes mellitus. We matched the RBC aggregability indices in both groups of diabetic patients and compared the obtained results with those in the healthy control group. We found that rheological disorders were considerably pronounced. The RBC aggregability index increased by 62 percent (p < 0.001) in type 1 and by 57 percent (p < 0.001) in type 2 diabetic patients as compared to the control group. However, there were insignificant differences of the RBC aggregability changes between the two groups of patients. Therefore we conclude that blood rheological disorders are similar in both types of diabetes mellitus. The disturbed blood fluidity related to the increased RBC aggregability in the microcirculation promotes, in particular, the development of legs gangrene in both types of diabetes mellitus.

Basic factors determining the hemorheological disorders in the microcirculation.

Hemorheological properties and disorders are very specific in the microcirculation since blood is actually not a fluid in the capillaries and in the adjacent arterioles and venules. This is because almost half of the blood volume constitutes the red and white blood cells whose size is commensurable with the microvessels lumen. Based on perennial investigations we concluded that the advancement of blood in capillaries is primarily dependent on the "structure" of the flowing blood that determines the resistance to blood advancement in the microvessels rather than on the well-known hydrodynamic relationships characteristic for the larger blood vessels. Basing on the perennial research of the hemorheological disorders in the microvessels we succeeded to specify the principal factors determining the blood flow resistance in the microcirculation. These factors are as follows: the erythrocyte enhanced aggregability > their deformability > the local hematocrit > the blood plasma viscosity. Solution of these theoretical problems is very important for the theory and practical medicine, since the blood rheological disorders in the microcirculation play a significant role in development and outcome of such essential diseases as the cerebral and cardiac infarcts, the diabetus mellitus, arterial hypertension, tumor grow, and many others.

Direct beneficial effect of insulin on blood rheological disorders in the microcirculation.

Under both the in vivo and in vitro conditions we investigated the insulin effect on the most significant factor disturbing the blood rheological disorders in the microcirculation, the red blood cell aggregability. The in vivo studies we carried out in the 42 insulin treated diabetic patients (diabetes mellitus type II), as well as conducted the in vitro investigations of the blood both of the diabetic patients (24) and of the healthy people (20) where the insulin was added to the blood ex vivo. The RBC aggregability in blood investigated with the "Georgian technique" was found significantly enhanced, by about 100 per cents in the diabetic patients. Under the in vivo conditions insulin administered intravenously decreased the RBC aggregability almost to the normal level in diabetic patients. In addition, in the in vitro studies we found that the insulin lowered significantly the RBC aggregability when it was significantly enhanced by addition of Dextran-500, as well as in the blood of patients with the ischemic brain infarcts. The decreasing effect on the RBC aggregability was observed even in the healthy control group where the RBC aggregability was in a normal range.

Regional and systemic hemorheological disorders during feet diabetic gangrene.

We investigated the RBC aggregability in the patients with the foot diabetic gangrenes: in the venous blood samples taken from the damaged foot before its amputation, as well as from the cubital vein (the systemic circulation). The RBC aggregability was investigated with the "Georgian technique" that is sensitive and provided us with direct and quantitative data. We found that the RBC aggregability was higher by about 20%, in the blood flowing from the gangrenous tissue than in the systemic circulation. Therefore, the sources of the systemic hemorheological disorders were the primarily damaged tissues. Taking into account that the blood is uninterruptedly flowing and mixing together in the whole circulatory bed we conclude that in the systemic circulation a certain compensatory mechanism provide for a partial normalization of the blood rheological properties, since the RBC aggregability never reaches the level in the blood of the healthy people.

Regional hematocrit changes related to blood flow conditions in the arterial bed.

Present study was aimed at specifying both the anatomical and physiological factors determining the regional hematocrit alterations. These latter were investigated in blood samples from specific vascular branches of rabbits, as well as from the skin and the jugular veins (reflecting the cerebral microcirculation) of humans. Principal findings were as follows: (1) Blood in the heart left ventricle has a higher hematocrit than blood flowing in the hind legs. (2) Blood flowing towards the cerebral vessels has a higher hematocrit than blood flowing to the hind legs. (3) Hematocrit in blood from the right brachial artery is higher than from the left one. (4) Analogous is the red cell/plasma relationship in the microcirculation from the humans' right and left hands' fingers. (5) Local hematocrit in the individual arterial branches of the rabbits' aortic arch is dependent on the blood flow velocity in them: the faster flow provides higher hematocrit in their lumen. (6) Microvascular hematocrit in rabbits was found significantly lowered during ischemia in the respective vascular beds. (7) Microvascular hematocrit in the human skin decreases during lowering of blood inflow, and vice versa, thus evidencing that the capillary hematocrit depends on the functional state of the feeding arterioles. We concluded, therefore, that the two basic factors determining the local hematocrit in arterial branches and in the respective microvascular networks are the anatomical outlines and the comparative velocities of blood flow in their lumina. However, in patients with strokes the hematocrit in blood flowing in the jugular veins was found lower than in blood from the carotid arteries. This might be related to the enhanced RBC aggregation and retention in the cerebral microvessels producing multiple blood stases in their lumina.

Local RBC aggregation disturbing blood fluidity and causing stasis in microvessels.

Experiments in rat mesenterium were carried out under conditions when both pressure gradient in the chosen microvessels and their diameters were preserved constant. All details of the hemorheological events were directly visualized and documented by usage of appropriate microscopic video techniques. Intensified RBC aggregation locally produced in individual capillaries, immediately disturbs the normal blood flow structure inside their lumina and deranges the rheological properties of blood flow in the microvessels, which slows down till a full stop. The RBC aggregates gradually grow up due to addition of new cells, which become compressed and appear homogeneous. This usually interferes with restoration of blood flow in capillaries. Further the RBC aggregates can move slowly towards veins, while the flow accelerates immediately as soon as the aggregates reach the larger venules.