Free radicals activity and blood rheology

Atherosclerosis is the major cause of morbidity and mortality in much of the world. Atherogenesis is a complex process and have three stages. The first stage is the fatty streak lesion. The second stage is fibrous plaque. And the final stage is the complex lesion which show evidence of thrombus formation. However thrombus formation is always a result of theologic disorders too. Rheologic properties are high depended from blood physical-and-chemical conditions including the concentration of serum lipids. The last are main target for free radicals action. Because atherosclerosis is always accompanied by increased free radical activity in blood we supposed that disorders of blood rheology are determined by mainly free radical influence. And those influence can contribute to the development of thrombotic conditions by constant parameters of blood coagulation. So the aim was to study the influence of lipid oxidation to hemorheology as possible risk-factor for the development of thrombotic complications. Low density lipoproteins (LDLP) were extracted with use of cold centrifugation from the blood of healthy volunteers. Then the part of them were oxidized to various degrees in a presence of cupric ions (2+). The oxidation degree was determined in test serum via the concentration of malone dialdehyde (later, MDA, nmol per mi of serum). For in vitro experiments non-oxidized or oxidized LDLP added in whole blood from healthy donors. In vitro models with antioxidants were used too. Rheology was analyzed with use of viscosimetry for plasma by shear rate 250 s(-1) and for whole blood by shear tate from 10 to 300 s(-1). Rotational viscosimeter AKR-2 (Russia) was used. By viscosity datas some hemorheologic parameters were calculated. Erythrocytes osmotic resistance was used for the estimation of membrane state in red blood cells. So the osmotic resistance of erythrocytes was as a marker of cell membrane damages. And nineteen patients after orthotopic heart transplantation were surveyed during initial stages of atherosclerotic lesion. These patients had the increase of lipids oxidation but had not disorders of blood coagulation and thrombophilic state. The values of thrombotic risk were calculated by software "Aggregate State of Blood" (Ver. 2.1; NRCS RAMS, 1995). For clear comparison each parameter in normal whole blood was accepted as 100 per cents. Experimental datas had comparative aspect. It was established that the degree of lipid oxidation play independent role for the development of hemorheologic disorders. Microrheology (erythrocytes-depended properties) are affected first and already in cases with MDA level in the borderline between normal and pathological values. For oxidized LDLP action the first target is erythrocytes membranes. Further increase of lipids oxidation affects plasma components - fibrinogen and albumin too. In all cases the reduction of blood fluidity has been arised. Pathologic changes appears in blood flow profile too. Just this condition can contribute to the development of thrombophilic state even by normal parameters of blood coagulation. Antioxidants protection of erythrocytes membranes allows to counteract to microrheologic disorders with further reduction of blood fluidity and, as consequence, to the development of thrombophilic state. Nevertheless this effect can be shown by low degree of lipids oxidation. Results of study contributes to an understanding of pathologic processes by atherosclerosis and by atherothrombosis.