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The microcirculation state was assessed in the group of patients with ischemic stroke (n = 30) and the control group of healthy individuals (n = 27) using laser Doppler flowmetry and the wavelet analysis of the amplitude-frequency range of microvascular blood flow oscillations combined with absorption spectros copy. The hemorheological parameters (blood and plasma viscosity, the degree of red blood cell aggregability and deformability) were assessed in both groups, as were their correlations with the microcirculation param eters. Decreased tissue perfusion (by 25%) and specific oxygen consumption (by 21%) were revealed in a cerebrovascular accident. Changes in the tone forming regulatory mechanisms of microcirculation of vasodi lating nature (decreased microvascular tone, activation of the secretory function of endothelium) may be regarded as a compensatory reaction aimed at maintaining the blood supply of organs and tissues in stroke. The blood viscosity increase in patients due to the plasma viscosity increase and increased red blood cell aggregability and their decreased deformability cause the blood flow to slow down and the wall shear stress to increase, which activates the endothelial secretory function and vasodilation of microvessels. Correlation between the rheological parameters and the passive (respiratory and cardiac) rhythm amplitudes was observed in the control group. In patients, the hemorheological parameters were correlated with the characteristics of the active factors of microvascular blood flow modulation (endothelial, neurogenic, and myogenic), which confirms the role of changed blood properties and regulatory tone forming mechanisms in the maintenance of tissue perfusion in cerbrovascular accidents.

Erythrocyte deformability and thus the efficiency of the oxygen delivery to tissues depends on three main factors: elasticity of cell membrane, viscosity of cytoplasm, and the erythrocyte surface/volume ratio. The membrane elasticity and stability most considerably contribute to the whole cell deformability. There are experimental data suggesting that erythrocyte deformability is regulated by intracellular signaling pathways. The aim of this work was to study the role of the adenylyl cyclase-cAMP systems and intracellular calcium signaling mechanism in the regulation of erythrocyte deformability. We found that stimulator of ade nylyl cyclase (AC) forskolin (10 -5 M) and cell penetrating cAMP analog dB cAMP (5 × 10 -5 M) increased erythrocyte deformability. Inhibitors of the phosphodiesterase (PDE) activity, such as isobutyl methylxan thine, vinpocetine, and cilostazol (10 -5 M), also increased the erythrocyte deformability, which provides another line of evidence of the cAMP involvement in the regulation of erythrocyte deformability. On the other hand, stimulation of Ca 2+ entry into erythrocytes induced by Ca 2+ ionophore A23187 (3 × 10 -6 M), sodium fluoride, or sodium vanadate considerably decreased the cell deformability, while blockade of the Ca 2+ entry into erythrocytes by verapamil (10 -5 M) increased their deformability. Mechanical stress of the erythrocyte membrane in the absence of extracellular Ca 2+ did not change the deformability, while the mechanical stress applied in the presence of Ca 2+ (50-200 μM) decreased deformability by 4-18%. On the whole, the obtained results suggest that for the increase in the erythrocyte deformability the AC-cAMP-PKA cascade has to be activated, while the pathway triggered by the Ca 2+ entry into the cells is required to lower the erythrocyte deformability (elasticity) and hence, to increase the whole cell membrane stability. It is possible that these pathways are coordinated at the PDE level.

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