[Haemodynamic role of blood-plasma circulating cell-free DNA and contained therein high-molecular-weight CpG-rich fraction in pathogenesis of arterial hypertension and atherosclerosis obliterans of carotid arteries].

The hydrodynamic resistance (HR) of blood is one of the components of the total peripheral resistance. High-molecular-weight DNA appears to decrease the HR in accordance with the Toms's effect. The present study was undertaken to investigate the HR and properties of cell-free DNA circulating in the blood plasma (hereinafter referred to as pDNA) of the control donors, patients suffering from either arterial hypertension (AH) alone or that combined with atherosclerotic lesions of the carotid arteries (CAs). Within the normal concentrations of pDNA, we revealed an inverse dependence of the HR thereupon and upon the content in pDNA of the high-molecular-weight CpG-rich fraction (CpG-DNA), i. e., a transcribed region of the ribosomal repeat (rDNA). A decrease or an increase in the pDNA concentration in all the patients examined was accompanied by an elevation of the rDNA concentration in the blood plasma. Exceeding a certain level thereof appeared to give rise to an increase in both the HR and arterial pressure (AP). Patients presenting with degree I essential AH were found to have a decreased endonuclease activity of the blood plasma, with the pDNA concentration being more than two-fold higher with no change in the rDNA content. Their HR appeared to be increased (p<0.01). Patients diagnosed as having degree II AH were characterized by a normal or decreased level of pDNA and an elevated content of pDNA, with the HR being slightly lowered. In patients presenting with atherosclerosis obliterans of the ACs, the initial manifestations of the lesions of the carotid arteries were typically revealed on the background of a lowered HR (p<0.05). All patients suffering from atherosclerotic lesions of the ACs could be subdivided into two groups, which in our opinion is probably associated with different various mechanisms of destructive damage to the arterial intima. In some of them, the pDNA concentration does not differ from the normal values, but in its composition, there is an increased content of rDNA, elevating as obliteration of the vessels' lumen increases, with the HR being decreased. The majority of them have degree II AH. In others, the pDNA concentration is by an order of magnitude higher than the normal values, while the rDNA content in pDNA is decreased, with the HR being elevated. Most of them have degree III AH. Pronounced and rough stenoses take an asymptomatic course in patients with decreased values of the HR and a slightly elevated level of pDNA and/or rDNA in the blood plasma. A higher level thereof leads to a rise in the HR and to the appearance of neurological symptomatology. Hence, CpG-DNA circulating in the composition of pDNA is a constantly acting endogenous blood factor decreasing the HR (the Toms's effect) and normalizing AP under physiological conditions, being however a cause of their increase and impairment of blood circulation in the pathogenesis of AH and atherosclerosis obliterans of the CAs.

Deltaran prevents an adverse effect of emotional stress on the course of cerebral ischemia in low-resistant animals.

Local cerebral blood flow in the left hemisphere decreased most significantly in low-resistant Wistar rats preexposed to emotional stress. Deltaran selectively increased blood flow in the left hemisphere and improved blood supply to neuronal activity unit of the brain in these animals. This drug prevented progressive decrease in local cerebral blood flow in both hemispheres during the acute stage of ischemia. The effect of Deltaran was related to modulation of collateral blood flow and adequate blood supply to neuronal activity unit in the brain tissue. Deltaran decreased the mortality rate (by 62%) and alleviated the symptoms of cerebral ischemia. The positive effect of Deltaran was more pronounced in the left hemisphere.

Correction of cerebral ischemia in low-resistant animals with an antistress drug Deltaran.

Deltaran decreased the amplitude of EEG slow waves and restored neuronal reactivity after carotid artery occlusion in Wistar rats sensitive to cerebral ischemia. Deltaran had no effect on local cerebral blood flow. This drug increased blood supply to a unit of neuronal activity in the brain of intact animals during the acute stage of cerebral ischemia, provided 100% survival rate of rats with cerebral ischemia, and prevented the development of neurological symptoms in survivors. Animal experiments proved the possibility of correcting cerebral ischemia with antistress drug Deltaran.

Individual resistance to cerebral ischemia and negative effect of emotional stress on the course of this disorder.

The ratio of low-activity and high-activity rats differed in autumn, winter, and spring litters. Initially more intensive cerebral blood flow in low-active rats and its more pronounced decrease after common carotid artery occlusion determined their higher sensitivity to cerebral ischemia (compared to high-activity animals). After 18-h immobilization stress cerebral blood flow decreased by 10-15%, which abolished the difference in the individual resistance to cerebral ischemia. Independently on emotional resistance, cerebral ischemia was not accompanied by the development of collateral blood flow in the acute period and caused death of 90% rats.

[Disregulation of collateral blood flow and lipid peroxidation abnormalities as a cause of negative influence of emotional stress on the course of cerebral ischemia]. / Dizreguliatsiia kollateral'nogo krovoobrashcheniia i narushenie perekisnogo okisleniia lipidov -- osnova negativnogo vliianiia émotsional'nogo stressa na techenie tserebral'noi ishemii.

Under normal conditions, local brain blood flow in young rats determined their individual resistance to ischemia and emotional stress. In low-activity rats predisposed to emotional stress, a level of blood flow was significantly (p<0.05) higher, comparing to high-active animals resistant to emotional stress. An exposure of rats to aggressive- and conflict situation for 18 h was followed by pronounced emotional stress accompanied by the reduction of local cerebral blood flow by 10-15% and abolished individual differences in resistance to cerebral ischemia. Collateral blood flow did not develop in pre-stressed rats during the acute period of cerebral ischemia. The mortality rate reached 90% independently of the animal emotional resistance. In ischemia after 2 h exposure to stress, differences were revealed in the intensity of lipid peroxidation in the brain of animals with divergent emotional resistance. Comparing to stress-resistant rats, in stress-predisposed animals, a level of malonic dialdehyde in the amygdale basal nuclei was 2-fold lower. The results suggest the differences in stress response in animals with various resistance to the effect of adverse factors.

[Hydrodynamic efficiency of various forms of free DNA]. / Gidrodinamicheskaia éffektivnost' raznykh form svobodnoi DNK.

DNA of blood plasma is the factor which corrects hydrodynamic resistance (HR) of blood flow and provides Thomes' effect. As comparative hydrodynamic effectiveness of various plasma DNA forms (nucleoprotein, thread and denaturated DNA isolated standardly from human leukocytes) remains unknown, the in vitro test identified HR of the flow of the above DNA forms weak solutions--10(-6) to 10(-5) g/ml--necessary for achievement of Thomes' effect in strictly similar hydrodynamic conditions warranting a turbulent flow (Re 8000). Thomes' effect was confirmed in blood samples in its absence in low-molecular solutions (glycerine) with the same asymptotic viscosity. It was found that HR of the flow of synthetic polymer solutions producing Thomes' effect depends on its initial concentrations. Hydrodynamic effectiveness in the used solutions of the nucleoprotein and DNA was high being comparable to that of the synthetic polymer widely used in production for obtaining Thomes' effect.

[Hemodynamic effect of plasma DNA]. / Gemodinamicheskii éffekt DNK plazmy krovi.

To reveal the hemodynamic effect of plasma DNA, the authors measured the concentrations of plasma DNA, the length of its molecular fragments, and hemodynamic resistance/Toms effect. The Toms effect was detected in all blood samples from 10 healthy donors and 39 patients without acute stroke caused by atherosclerosis of the head great arteries with and without arterial hypertension. There was a clear inverse relationships between the plasma concentrations of DNA which had only long-molecular fragments in healthy persons and the hemodynamic resistance of its blood flow samples. The patient blood plasma had significant increased DNA concentrations but their molecular fragments were long and short. Inverse relationships between the plasma DNA concentration and the hemodynamic resistance of the patients' blood flow samples had a less correlation coefficient due to the high proportion of short DNA molecular fragments. The Toms effect was shown in the DNA solution prepared only from human funic blood where the DNA molecular fragments were long. The Toms effect was absent in the solutions prepared from the commercial cattle or salmon sperm DNA which contained shorter DNA molecular fragments. It is concluded that plasma DNA has a hemodynamic effect and the origin of long-molecular fragments of DNA which is typical for healthy young persons and short DNA molecular fragments that additionally appear in patients with vascular disorders is different.

[Effect of the nootropic agent cerebrolysin in cerebral ischemia in rats with varying behavioral reactions in the open field test]. / Vliianie nootropa--tserebrolizina pri ishemii mozga u krys s raznymi povedencheskimi reaktsiiami v teste otkrytogo polia.

Open field tests were made on 489 white male rats to distinguish subgroups by baseline higher nervous activity (HNA) to study the effects of cerebrolysin (EBEVE, Austria) on relationships between neuronal activity and cerebral blood supply in normal cerebral circulation (CC) and in acute brain ischemia. Local CC and EEG were measured by laser doppler flowmeter and read from the same point gauge. CC/EEG index was calculated. Cerebrolysin was injected i.p. in a dose 0.3 ml/100 g body mass. Brain ischemia was provoked by occlusion of the common carotid arteries. Neurological symptoms were estimated according to the McGrow scale. Also, 24-h lethality was registered. It was confirmed that cerebrolysin, as an active nootrop, enhances EEG. This effect takes place both in intact and brain ischemia rats. It was also found that cerebrolysin has different effectiveness dependent on the animal's behavior in the open field test, that blood supply to the brain does not increase in cerebrolysin-activated HNA. In stable circulation, this was compensated due to cerebral metabolic reserve, but in intensive EEG activation, recorded by CC/EEG index, cerebrolysin reduces cerebral blood supply aggravating acute brain ischemia.

[New findings concerning pathogenesis of disorders of cerebral circulation]. / Novoe v patogeneze narushenii mozgovogo krovoobrashcheniia.

The data about the role of blood flow in atherosclerosis development were examined. The aim of the study was determination of hydrodynamic blood resistance and Toms effect in patients with ischemic disorders of cerebral circulation in different periods of the disease. 45 patients with atherosclerotic damages of major arteries of head were observed. Such damages were combined with arterial hypertension in 32 individuals. The value of hematocrit, asymptotic viscosity, hydrodynamic resistance and Toms' effect were determined in blood as well as levels of cholesterol, beta-lipoproteins and platelets. The presence of Toms' effect was found in blood samples of both patients and controls. There was a significant increase of hydrodynamic blood resistance in all the patients as compared to control group. The patients with ischemic disorders of cerebral circulation were compensated by their own blood factor in less degree in acutest and acute periods than later. Low values of Toms' effect in separate patients were prognostic sings for good restoration of neurologic functions; higher values were observed in patients with arterial hypertension. The conclusion was made that hemodynamic properties of blood flow may be considered as predictors of the severity of the course of cerebral circulation disorders.

[Prognostic behavioral criteria and the characteristics of the cerebral blood flow in rats with different sensitivities to emotional stress]. / Prognosticheskie povedencheskie kriterii i osobennosti mozgovogo krovotoka u krys s razlichnoi ustoichivost'iu k émotsional'nomu stressu.

In anesthetised Wistar adult male rats, a model of circulatory brain ischemia was created. A behavioural difference as well as a difference in normal focal cerebral blood flow (CBF), were revealed between rats resistant against and predisposed to emotional stress. The mortality level was 10% in former rats and 27% in latter ones.

[Diminished experimental alimentary atherogenesis under the influence of polymers that decrease the hydrodynamic resistance of the blood]. / Umen'shenie éksperimental'nogo alimentanogo aterogeneza pod vliianiem polimerov, snizhaiushchikh gidrodinamicheskoe soprotivlenie krovi.

The experiments on adult rabbits have demonstrated that high-cholesterol diet given to the animals for 3 months causes a severe hypercholesterolemia and disseminated aortic lesion due to the formation of numerous fatty streaks and plaques of atherosclerotic genesis. The simultaneous intravenous injection of a special linear high molecular-weight polymer solution, which reduces hydrodynamic resistance once a week leads to a significantly less atherogenesis in the same hypercholesterolemia. The highest effect was observed in the descending portions of the aorta and just after its bifurcation, i.e. in the areas of the least unsteady blood flow.

[Comparative characterization of morphologic changes in animal brain after normo-, hypobaric hypoxic hypoxia and hypobaric normoxia]. / Sravnitel'naia kharakteristika morfologicheskikh izmenenii mozga zhivotnykh posle normo-, gipobaricheskoi gipoksicheskoi gipoksii i gipobaricheskoi normoksii.

In three series of experiments on 16 randomly inbred adult male rats, specific features of morphological changes in the brain were studied 3 days following the tests of animals for high- or low-resistance to hypoxic hypoxia (HH) during hypobaric HH (Series I), normobaric HH (Series II), and hypobaric normoxia (Series III). The conventional testing was found to result in changes in the rat brain, which were caused both by HH and decompression. The more sparing procedure is testing animal during normobaric HH which eliminates the impact of decompression whose damaging action was pronounced in hypobaric normoxia. Thus, the sensitivity of rats to HH should be detected, by using the least brain-traumatizing modified procedure--normobaric HH.

Blood flow hydrodynamic resistance in patients with ischaemic stroke or vascular encephalopathy and possibilities of its correction in vitro.

In order to determine the patient blood flow hydrodynamic properties in terms of the Toms-effect, the time blood flow was measured in special apparatus twice: (1) before and (2) after addition of poly(ethylene oxide) WSR-301 (Union Carbide, USA) in concentration of 2 x 10(6) g/ml of blood sample (50 ml with 500 units of heparin) taken from 26 patients with acute ischaemic stroke, 8 patients with vascular encephalopathy after stroke, 5 patients with vascular encephalopathy following atherosclerosis with or without arterial hypertension. The blood samples taken from 8 healthy persons formed the control group. Haematocrit (HCT) and asymptotic blood viscosity were studied also. It was established that hydrodynamic blood flow resistance (HBFR) did not depend on HCT and viscosity, but was significantly higher in all patient groups than in normal persons (p less than 0.05). Addition of polymer solution decreased HBFR of patient blood more intensively that in the control group. We believe that it indicates an insufficiency of an unidentified factor in native human blood.

[Effect of stepped isovolemic hemodilution on some parameters of systemic and cerebral hemodynamics under normal conditions and in a sharp rise of arterial pressure]. / Vliianie stupenchatoi izovolemicheskoi gemodiliutsii na nekotorye parametry sistemnoi i i tserebral'noi gemodinamiki v norme i pri ostrom pod "eme arterial'nogo davleniia.

It was demonstrated in rabbit experiments that in decrease of the hematocrit value by more than 10% the increase of arterial pressure induced by intravenous noradrenaline injection and its additional rise are significantly higher than in the controls. In spite of that, the breakthrough of autoregulation of local cerebral blood flow occurred much less frequently, was less pronounced, and attended by significantly less damage to the permeability of the blood-brain barrier to labelled blood albumin. This phenomenon can be explained by the fact that in reduced blood viscosity the pseudoturbulence of its flow, and the hydrodynamic resistance of blood increase due to which it reaches the microcirculatory bed at a lesser pressure than in the controls. The results of the study substantiate the expediency of blood-letting as a therapeutic measure for patients with hypertensive disease, in hypertensive crises also.

[Effect on the systemic hemodynamics of polymers that decrease hydrodynamic resistance]. / Vliianie na sistemnuiu gemodinamiku polimerov, snizhaiushchikh gidrodinamicheskoe soprotivlenie.

It has been shown that intravenous injections of drug-reducing polymers (at a dose of 2 x1 0(-6) g/ml) to rabbits produced a decrease in the total peripheral resistance with an increase in the cardiac output and simultaneous diminution of the mean blood pressure. These hemodynamic effects did not depend on vasodilatation as it had previously been shown. The alterations were retained for not less than 72 hours after one polymer injection; the effects were due to the influence of polymers on the flow structure.

[Quantitative morphometric evaluation of the muscular coat of arteries taking into account their functional state]. / Kolichestvennaia morfometricheskaia otsenka myshechnoi obolochki arterii s uchetom ikh funktsional'nogo sostoianiia.

The method is suggested for the quantitative characteristics of dynamic vascular tone. It allows the determination of a degree of vascular vasoconstriction as a definite value--an index. This index is determined as real area of vascular cross-sections to their maximum possible area ratio with the inner elastic membrane fully straightened. The index determined in such a way permits to assess quantitatively the degree of vascular vasoconstriction, which is independent of the vascular diameter.