Mikhail Blagonravov | People's Friendship University of Russia (original) (raw)

Papers by Mikhail Blagonravov

Research paper thumbnail of Daytime Exposure to Blue Light Alters Cardiovascular Circadian Rhythms, Electrolyte Excretion and Melatonin Production

Pathopysiology, 2022

Artificial light is characterized by certain features of its impact on the body in terms of its s... more Artificial light is characterized by certain features of its impact on the body in terms of
its spectral distribution of power, duration of exposure and intensity. Short waves, perceived as
blue light, are the strongest synchronizing agent for the circadian system. In the present work, we
investigated the features of the circadian rhythms of blood pressure (BP), heart rate (HR), the excretion
of electrolytes and the secretion of melatonin in normotensive (Wistar–Kyoto) and hypertensive
(SHR) rats under the action of monochromatic blue light in the daytime period. It was found that
the exposure of Wistar–Kyoto rats to monochromatic blue light was accompanied by a significant
decrease in nighttime and 24 h systolic BP. The most remarkable changes are characteristic of the
HR in SHR rats under monochromatic light. A significant decrease in HR in each time period was
found, but the predominance of nighttime over daytime values remained in SHR animals. There
was also a significant increase in the mesor of the HR in SHR rats. Additionally, the amplitude of
diastolic BP and HR, as well as the range of oscillations in HR, were significantly increased compared
with the standard light pattern. In contrast to SHR rats, the regulation of the circadian rhythms
in Wistar–Kyoto rats was more flexible and presented more changes, which may be aimed at the
adaptation of the body to environmental conditions. For Wistar–Kyoto rats, an increase in the level of
excreted electrolytes was observed under the action of monochromatic light, but no similar changes
were found in SHR rats. For Wistar–Kyoto rats, a significant decrease in the urine concentration of
aMT6s in the daytime and nighttime periods is characteristic, which results in the loss of the circadian
rhythm. In SHR rats, there was a significant decrease in the nighttime content of aMT6s in the urine,
while the daytime concentration, on the contrary, increased. The obtained data demonstrate that
prolonged exposure to monochromatic blue light in the daytime period affects the circadian structure
of the rhythms of the cardiovascular system, the rhythm of electrolyte excretion and the production
of epiphyseal melatonin in wild-type and hypertensive animals. In SHR rats, the rhythms of BP and
HR exhibit a more rigid pattern.

Research paper thumbnail of The effect of bright light on blood pressure and heart rate in essential hypertension

Research paper thumbnail of Limitations of Seasonal Pattern Assessment Questionnaire and Development of Shastun's Questionnaire for Assessment of Seasonal Affective Disorders, Among Namibian Students in Moscow

Background. The environmental transition from one country to another after migration may be also ... more Background. The environmental transition from one country to another after migration may be also associated with change in seasons, weather and climate as well as in psychosocial stress which may put a greater demand on physiology and metabolism of migrants that may predispose to cardiometabolic risk. This is commonly seen among students of the People's Friendship University of Russia. Moscow. This study examines the validity of the newly developed questionnaire by Dr Shastun, for assessment of seasonal affective disorder (SAD) among students of Namibia studying at Moscow. Subjects and Methods. After approval by the Review board/ethics committee of Faculty of Medicine, People's Friendship University of Russia, Moscow and written informed consent, subjects were recruited for this study. The study involved; Namibian students migrating to Russia while studying in Moscow. Of 87 students from Namibia, all of them volunteered to participate in the study. Seasonal affective disorder (SAD) was studied by Shastun's questionnaire and Seasonal Pattern Assessment Questionnaire (SPAQ). The SPAQ is a brief, self-administered screening tool for seasonal affective disorder (SAD) which may have limitations. The criterion for diagnosis of SAD was a score of 11 or higher on this scale which means the highest level of SAD. The diagnosis SAD was also made by administering Shastun's questionnaire. Results. The results indicate that clinical manifestations indicating SAD were rare while the students were in Namibia, which showed significant increase after migration to Russia and staying minimum for one year. Hypersomnia, overeating and carbohydrate craving were common manifestations of SAD. The prevalence of SAD by Shastun's questionnaire was significantly lower compared to frequency of SAD by SPAQ, respectively (11.9% vs. 18.5%, P ≤ 0.05). The number of sunny days per year and the average annual temperature of the region of stay appear to be the most significant confounders and for the occurrence of cardiometabolic risks among students.

Research paper thumbnail of Effect of Phosphocreatine and Ethylmethylhydroxypyridine Succinate on the Expression of Bax and Bcl-2 Proteins in Left-Ventricular Cardiomyocytes of Spontaneously Hypertensive Rats

We studied the effect of phosphocreatine and ethylmethylhydroxypyridine succinate on the expressi... more We studied the effect of phosphocreatine and ethylmethylhydroxypyridine succinate on the expression of Bax and Bcl-2 proteins in left-ventricular cardiomyocytes of spontaneously hypertensive rats (SHR). Both drugs have no effect on the expression of Bcl-2, but significantly reduce the level of Bax protein (phosphocreatine produces more pronounced effect). These data attest to an important role of energy defi cit and oxidative stress in the induction of cardiomyocyte apoptosis in genetically determined arterial hypertension.

Research paper thumbnail of Specific Features of Electrolyte Excretion at the Early Stages of Arterial Hypertension in SHR Rats

Daytime and nighttime systolic and diastolic BP was recorded in 23-week-old SHR and Wistar rats b... more Daytime and nighttime systolic and diastolic BP was recorded in 23-week-old SHR and Wistar rats by telemetric monitoring. Urine concentrations of sodium, potassium, and calcium were determined in SHR rats during of light (07.00-19.00 h) and dark hours (19.00-07.00 h) at the age of 18, 19, 20, 21, 22, and 23 week; 23-week-old Wistar rats were used as the control. At early stages of the experiment, urine sodium concentration was elevated in SHR rats both at daytime and at night. Thereafter, this value declined and by 22-23 week was significantly lower than in normotensive Wistar rats, but only during daytime. Daytime potassium concentration significantly surpassed the control level during weeks 18-19 of the experiment, but later, a tendency to a decrease in this parameter was observed. Daytime calcium content in SHR rats did not significantly differ from the control throughout the experiment. At night, this value exceeded the control level by more than 2 times during weeks 18-19, but then returned to the level observed in normotensive animals.

Research paper thumbnail of Influence of geomagnetic activity and earth weather changes on heart rate and blood pressure in young and healthy population

International Journal of Biometeorology, 2017

There are many references in the literature related to connection between the space weather and t... more There are many references in the literature related to connection between the space weather and the state of human organism. The search of external factors influence on humans is a multi-factor problem and it is well known that humans have a meteo-sensitivity. A direct problem of finding the earth weather conditions, under which the space weather manifests itself most strongly, is discussed in the present work for the first time in the helio-biology. From a formal point of view, this problem requires identification of subset (magnetobiotropic region) in three-dimensional earth's weather parameters such as pressure, temperature, and humidity, corresponding to the days when the human body is the most sensitive to changes in the geomagnetic field variations and when it reacts by statistically significant increase (or decrease) of a particular physiological parameter. This formulation defines the optimization of the problem, and the solution of the latter is not possible without the involvement of powerful metaheuristic methods of searching. Using the algorithm of differential evolution, we prove the existence of magnetobiotropic regions in the earth's weather parameters, which exhibit magneto-sensitivity of systolic, diastolic blood pressure, and heart rate of healthy young subjects for three weather areas (combinations of atmospheric temperature, pressure , and humidity). The maximum value of the correlation confidence for the measurements attributable to the days of the weather conditions that fall into each of three magnetobiotropic areas is an order of 0.006, that is almost 10 times less than the confidence, equal to 0.05, accepted in many helio-biological researches.

Research paper thumbnail of Cardiomyocyte BECN1-dependent autophagy in acute overload of the left ventricle

FEBS Journal, 2017

Hemodynamic overload of the left ventricle of the heart is accompanied by activation of some mech... more Hemodynamic overload of the left ventricle of the heart is accompanied by activation of some mechanisms responsible for regulated cell death including apoptosis. In the recent years there has been an increasing interest to cardiomyocyte autophagy, which may be a phenomenon involved in programmed (or
regulated) death in some cases, but might also have reparative potential in other circumstances providing cell survival at the expense of its internal resource mobilization. In this work BECN1-dependent cardiomyocyte autophagy was evaluated by the content of Beclin 1 (BECN1) in cardiomyocytes without morphological
evidence of plasma membrane damage in rabbit left ventricular myocardium on 1, 3 and 5 days of acute hemodynamic overload caused by narrowing of the ascending aorta by 1/3 of its initial diameter. Activity of cardiomyocyte autophagy was assessed on the basis of BECN1 content estimation immunochemically
with the use of primary goat polyclonal antibodies (SantaCruzBiotechnology, Inc., USA). It was shown that the
content of BECN1 was rather low in the control group (2.77 vol.%) and significantly decreased (0.54 vol.%) on day 1 after the onset of cardiac overload compared with the controls. On day 3 there was a further decrease in BECN1 in cardiomyocytes (0.20 vol.%). On day 5 this index negligibly increased (0.38 vol.%), but still remained significantly lower in comparison with controls. It was also found that intensity of positive stain was
much higher in the myocardial sites with denser vascular tree. It might be suggested that cardiomyocyte autophagy is a mechanism of cell resource mobilization in the intact myocardium rather than regulated cell death. Its inhibition under acute cardiac overload is most probably due to a severe energy deficit. The publication was financially supported by the Ministry of Education and Science of the Russian Federation (the Agreement No.02.A03.21.0008).

Research paper thumbnail of The polyamine exchange modulating compounds as anticancer agents

FEBS Journal, 2017

A deviation in polyamine (PA) metabolism is observed in various tumors in comparison with normal ... more A deviation in polyamine (PA) metabolism is observed in various tumors in comparison with normal tissues. In this regard, the PA exchange is considered as a target for the drug design of potential anti-tumor agents. The compounds activating PA catabolism are supposed to cause production of cytotoxic PA-metabolites
such as H2O2, acrolein, NH3 and thus to be potential anticancer agents. We suggest 3 main criteria for the primarily selection of PA-exchange modulating compounds. They must inhibit or at least not activate PA biosynthesis, activate PA catabolism, and show good membrane permeability. We have tested 30 different
compounds. The ODC and PAO activities were measured according to the standard PA protocols. The membrane permeability was evaluated through a standard PAMPA procedure. Cell growth inhibition was tested in a modified MTT-test in such cancer cell lines as PC3, MCF-7, MEL-7. Correlations between the
cytotoxic activity and membrane permeability were shown in different groups of compounds for all cell lines with the highest one for MEL-7. A correlation between the cytotoxic activity and spermine oxidation was shown in the group of copper complexes for MCF-7. The most cytotoxic was copper complex with the fluoroaniline derivative. Its IC50 was found to be in the range of 000,1 M. It showed PA biosynthesis inhibition, PA oxidation activation and good permeability as well. As the antiproliferative effect is supposed to be mediated by PA themselves being thesource of cytotoxic agents, the cell sensitivity is expected to be
PA level-dependent. However PC3 cells were the most sensitive to these compounds, although their initial PA levels are lower than those in MCF-7 cells. Further investigations are necessary for this group of compounds to justify it as potential anticancer agents. The publication was financially supported by the Ministry of
Education and Science of the Russian Federation (the Agreement No.02.A03.21.0008).

Research paper thumbnail of Distribution of the EDNRA H323H polymorphic genetic marker of cardiovascular diseases among populations of Syria, and Central Russia

FEBS Journal, 2017

Endotheline-1 is a potent vasoconstrictor that exerts this effect through ETA receptors; much evi... more Endotheline-1 is a potent vasoconstrictor that exerts this effect through ETA receptors; much evidence suggests that genetic variations in the EDNRA gene encoding ETA receptors may play a role in the pathogenesis of many cardiovascular diseases. The ethnic characteristics of the distribution of the EDNRA gene polymorphism may influence the development of these disorders in different populations; therefore we investigated for the first time the distribution of the synonymous polymorphism H323H (T>C) of the EDNRA gene (rs5333) among 50 Arab Syrians with the mean age of 26.19 � 8.03 years and 59 Russians from Central
Russia (19.67 � 1.96). The genotypes were determined with the use of PCR-RFLP (restriction fragment length polymorphism). The C allele frequency of the H323H polymorphism in Syrians and Russians was 27% and 8%, respectively. The genotype frequencies were in Hardy-Weinberg equilibrium in both populations (P > 0.05). The TT, TC and CC genotype frequencies were 58%, 30% and 12% among Syrians and 84.75%, 15.25%, 0% in the Russian population, respectively. A significant difference was found in the H323H genotype distribution
between Russians and Syrians (P = 0.011), as well as in allelic distribution (X2 = 11.22; P = 0.0008). These results show that the distribution of the H323H EDNRA polymorphism among Syrians and Russians should be investigated in larger samples, and considered in the further study of genes associated with cardiovascular
diseases. The publication was financially supported by the Ministry of Education and Science of the Russian Federation (the Agreement No.02.A03.21.0008).

Research paper thumbnail of Comparative study of the biocompatibility of polydioxanone and polyglycolide absorbable meshes for hernia and pelvic defects repair

FEBS Journal, 2017

The recurrence frequency of tension-free hernia repair with synthetic unresorbable and resorbable... more The recurrence frequency of tension-free hernia repair with synthetic unresorbable and resorbable mesh-implants compared to plastic surgery by own tissues decreased from 54% to 16%, but the frequency of mesh-related complications achieved 32%. By now there is no ideal prosthesis, so the development of a fully absorbable synthetic mesh implant is an effective way to solvethis problem. The aim of the study was to assess the biocompatibilityof polydioxanone (PDO) and polyglycolide (PGA) mesh implants. In vitro evaluation of cytotoxicity of mesh materials was performed by MTT assay. Evaluation of in vivo
biocompatibility of meshes was carried out on rat full-layer abdominal wall defect model. On day 3, 10, 30 and 60 after surgery tissues were collected for macroscopic, tensiometric, morphometric, immunohistochemical and western blot studies. MTT assay showed that both meshes did not possess cytotoxic properties.
In vivo experiment showed significant difference in adhesion intensity between the groups: PDO caused less adhesion score on day 3, 30, and 60. The resorption rate also differed: PGA filament area reduced by 36.5 � 4.7% vs 17.4 � 2.3% for PDO filament area. Maximal capsule thickness was observed in PGA on day 10 and 30 after the surgery, while PDO and Permacol capsules were thinner and almost didn’t change throughout the
whole experiment. PDO, PGA and Permacol meshes induced complex differences in the type of FBR over the time course of implantation. PDO evoked a milder early inflammatory response than other meshes. Significantly higher number of FBGC and Langhans cells were apparent throughout the time course in
PGA group. PDO led to better tissue integration and new collagen deposition compare to PGA. PDO provided better vascularization compared to Permacol. PDO mesh has higher biocompatibility than PGA mesh or even Permacol. The publication was financially supported by the Ministry of Education and Science of the Russian Federation (the Agreement No.02.A03.21.0008)

Research paper thumbnail of Melatonin Production in Essential Hypertension Under Common and Modified Light Schedules

Neuropsychobiology: 29-th Annual Meeting of the Society for Light Treatment and Biological Rhythms, 2016

Objectives: According to numerous data, the pathogenesis of cardiovascular diseases is associated... more Objectives: According to numerous data, the pathogenesis of cardiovascular diseases is associated with desynchronization of biological rhythms. Nowadays many people are exposed to excessive light at night which results in the inhibition of melatonin secretion by the pineal gland. In this study we explored the biosyn-thesis of epiphyseal melatonin under extended light exposure in essential hypertension. Methods: Experiments were carried out on male rats of SHR (hypertensive) and Wistar (normotensive) strains. Two different light-dark schedules were modeled: 12 hour light / 12 hour darkness with light on at 7.00 a.m. and off at 7 p.m. (12:12) and 16 hour light / 8 hour darkness with light on at 5.00 a.m. and off at 9.00 p.m. (16:8). Wistar rats were kept under 12:12 light-dark schedule, SHR rats were exposed to both 12:12 and 16:8 schedules. Melato-nin production was assessed by measuring urinary concentrations of its stable metabolite – 6-Sulfatoxymelatonin (6-SMT). Urine collection was performed in metabolic cages twice for 24 hour period – during the daytime and nighttime. It is well known that uri-nary concentration of 6-SMT correlates with the total melatonin blood level [Griefahn et al., 2001; Rapoport S.I. et al., 2009]. Concentration of 6-SMT in animal urine was determined using ELISA kit for 6-Sulfatoxymelatonin (Buhlmann Laboratories AG, Swit-zerland). Results: It was found that daytime urinary concentration of 6-SMT was significantly lower in comparison with the nighttime values in hypertensive rats exposed to both 12:12 and 16:8 light-dark schedules. Daytime 6-SMT concentration was 25.5 ± 1.49 ng/ ml in normotensive Wistar rats and it was significantly decreased to 16.27 ± 1.23 and 14.55 ± 1.32 ng/ml in SHR hypertensive rats kept under 12:12 and 16:8 light-dark schedules respectively. There was also an increase in the difference between day and night 6-SOMT in hypertensive rats kept under both light-dark regimens compared with controls. Meanwhile no difference in daytime 6-SMT urine contents was seen under light regimen 12:12 in comparison with 16:8 between the two groups of SHR rats. As regards nighttime, the values of urinary 6-SMT in Wistar rats, SHR rats under 12:12 and 16:8 light-dark regimens were as follows: 32.74 ± 2.78, 30.37 ± 2.54 and 26.08 ± 2.35 ng/ml with no significant differences between animal groups. Conclusions: The study results suggest the rate of daytime epiphyseal melatonin production is markedly lower under increased blood pressure. There was no significant effect of extending light exposure from 12 to 16 hours within the 24 hour period on melatonin biosynthesis by the pineal gland in essential hyper-tension.

Research paper thumbnail of Element Status of Students with Different Levels of Adaptation

Bulletin of Experimental Biology and Medicine, 2017

The element status was studied in students with different levels of adaptation determined by the ... more The element status was studied in students with different levels of adaptation determined by the parameters of cardiointervalography. The content of chemical elements in the hair was measured by atomic emission and mass spectrometry. In students whose autonomic status was characterized by sympathicotonia, the level of cobalt in the hair was significantly higher, while the levels of manganese and magnesium were lower than normal. The content of selenium in the hair was 2.3 times lower in the study group in comparison with the median level in Russia. The content of toxic elements did not exceed the normal. Significant positive correlations between hair content of magnesium and calcium and between potassium and sodium were revealed.

Research paper thumbnail of Characteristics of General Pathological Processes in the Lungs Following Clozapine Poisoning Experimental Studies

Obshchaya Reanimatologiya, 2017

The aim of the study: to study general pathological processes in the lungs in different time afte... more The aim of the study: to study general pathological processes in the lungs in different time after acute clozap
ine and combined clozapine+ethanol poisonings. Materials and methods. The experiments were performed on 25 outbreed male rats. The animals were divided into 5 groups: 1) reference (intact rats); 2) clozapine poisoning, 3 hours; 3) clozapine poisoning, 24 hours; 4) combined clozapine and ethanol poisoning, 3 hours; 5) combined clozapine and ethanol poisoning, 24 hours. Clozapine
was administered orally at a dosage of 150 milligrams per kilogram of the animal weight under anesthesia (chlorolase); alcohol was administered with clozapine orally at a dosage of 5 milliliters per kilogram of the animal weight. Animals of all these groups sacrificed by decapitation. Lung tissue samples were examined by light microscopy using a microscope Nikon Eclipse E%400 with a video system based on camera Watec 221S (Japan) at a 400x magnification. We evaluated the presence of the following signs: circulatory disturbances (hyperemia, hemorrhage), presence of atelectasis and dystelectasis, emphysema, cellular response (increased white blood cells count), desquamation of epithelium into the lumen of the bronchi, sludge. A morphometric analysis was performed using a grid developed by G. G. Avtandilov. The following signs were evaluated (volume percent, vol.): the area of the alveoli, intraalveolar septi, vessels, white blood cells, the percentage of white blood cells in the intraalveolar septi , the area of the edema and dystelectasis. Results. the following histologic signs were found 3 hours after clozapine poisoning: desquamation of epithelium into the lumen of the bronchi; cellular response (increased white blood cells count); presence of atelectasis and dystelectasis; thickening of intraaveolar septi due to edema; infiltration of intraalveolar septi by WBCs. Atelectasis and dystelectasis in ulmonary parenchyma and infiltration with WBC were observed 24 hours after clozapine poisoning. In the group of animals treated with ethanol and clozapine and decapitated 3 hours after the poisoning the following histological signs were detected: desquamation of epithelium into the lumen of the bronchi, the secret in the lumen of the bronchi, cellular response, atelectasis and dystelectasis, perivenular hemorrhages, hemorrhages into the alveoli, hemorrhages into intraalveolar septi, dilation of the lumen of the bronchi, the presence of sludge, thickening of intraalveolar septi (due to infiltration with WBCs, detachment of the endothelium in blood vessels. Arterial hyperemia, cellular response (increased of WBC count), atelectasis and dystelectasis, and thickening of intraalveolar septi were found 24 hours after combined ethanol and clozapine poisoning. In all study groups the lumen of the alveoli was significantly smaller as compared to the reference group, but the area of the intraalveolar tissue, on the contrary, was significantly greater. The total area of pulmonary microvessels did not differ significantly from the reference group 3 hours after clozapine poisoning. It became significantly higher 24 hours after the poisoning. A significant increase in this parameter vs. the reference group was found both 3 and 24 hours after the administration of the combination of clozapine with ethanol by animals. Conclusion. In clozapine and clozapine + ethanol poisoning, a certain complex of general pathological processes in lungs develops. There are alteration of bronchial epithelium and the vascular endothelium, circulatory disorder, increased vascular permeability, infiltration of intraaveolar septis. Morphological and immunoreactive changes can be used for valuation of severity of general pathological process in acute clozapine and clozapine + ethanol poisonings and determination of the exact time of the poisonings.

Research paper thumbnail of Cardiomyocyte Autophagia and Morphological Alterations in the Left Ventricular Myocardium during Acute Focal Ischemia

Bulletin of Experimental Biology and Medicine, 2016

In experiments on rabbits we evaluated the intensity of cardiomyocyte autophagia by the level bec... more In experiments on rabbits we evaluated the intensity of cardiomyocyte autophagia by the level beclin-1 protein and morphology of the left ventricular myocardium on days 1, 3, and 5 after the onset of focal ischemia caused by ligation of the descending branch of the left coronary artery. The morphological alterations in the left ventricular myocardium were accompanied by intensifi cation of cardiomyocyte autophagia, which attained maximum on postligation day 1.

Research paper thumbnail of Expression of Bax Protein and Morphological Changes in the Myocardium in Experimental Acute Pressure Overload of the Left Ventricle

Bulletin of Experimental Biology and Medicine, 2016

The expression of Bax protein, marker of intracellular pathway of apoptosis initiation, in viable... more The expression of Bax protein, marker of intracellular pathway of apoptosis initiation, in viable left ventricular cardiomyocytes and morphological changes in the myocardium in acute pressure overload of the left ventricle were studied in experiment on male rabbits. The content of Bax protein in the cardiomyocyte cytoplasm decreased, this indicating that the mitochon-drial pathway was not involved in the realization of the apoptotic program. This decrease was associated with manifest destructive changes in the left ventricular myocardium.

Research paper thumbnail of Features of the Structure of the Circadian Rhythm of Blood Pressure and Heart Rate under Genetically Determined Hypertension in the Experiment

Bulletin of Experimental Biology and Medicine, 2015

In SHR rats of different ages (22, 26, 30, 34, and 38 weeks), continuous 24-h telemetric monitori... more In SHR rats of different ages (22, 26, 30, 34, and 38 weeks), continuous 24-h telemetric monitoring of BP and HR was performed. The amplitude and power of oscillations of diastolic BP signifi cantly decreased at the later stages of arterial hypertension (38 weeks), which was considered as a poor prognostic marker. We also observed a signifi cant decrease in the mean daytime, nighttime, and maximum HR and mesor on weeks 30 and 34, but not on week 38, which can refl ect triggering of the adaptive response followed by its exhaustion.

Research paper thumbnail of Effect of Phosphocreatine and Ethylmethylhydroxypyridine Succinate on the Expression of Bax and Bcl-2 Proteins in Left-Ventricular Cardiomyocytes of Spontaneously Hypertensive Rats

Bulletin of Experimental Biology and Medicine, 2015

We studied the effect of phosphocreatine and ethylmethylhydroxypyridine succinate on the expressi... more We studied the effect of phosphocreatine and ethylmethylhydroxypyridine succinate on the expression of Bax and Bcl-2 proteins in left-ventricular cardiomyocytes of spontaneously hypertensive rats (SHR). Both drugs have no effect on the expression of Bcl-2, but significantly reduce the level of Bax protein (phosphocreatine produces more pronounced effect). These data attest to an important role of energy defi cit and oxidative stress in the induction of cardiomyocyte apoptosis in genetically determined arterial hypertension.

Research paper thumbnail of Characteristics of Circadian Rhythm of Blood Pressure during Long-Term Hypertension Development in SHR Rats

Bulletin of Experimental Biology and Medicine, 2013

The specifi c features of circadian rhythm of BP were investigated in freely moving male SHR rats... more The specifi c features of circadian rhythm of BP were investigated in freely moving male SHR rats using telemetry monitoring technique. BP was recorded in the abdominal aorta according to 24-h/4-month schedule. The data were obtained from 22, 26, 30, 34, and 38-week-old animals. Normotensive Wistar rats (22 weeks) served as the control. It was found that the mean 24-h, daytime, and nighttime systolic and diastolic BP in hypertensive rats signifi cantly surpassed the control throughout the observation period and practically did not change during prolonged hypertension. Some prognostically negative changes in the circadian rhythm of the basic hemodynamics system parameters appeared with time. For instance, the maximum 24-h systolic BP signifi cantly increased in comparison with the initial level.

Research paper thumbnail of Energy Deficit as a Possible Factor for the Induction of Caspase-Dependent Apoptosis in Left Ventricular Myocardial Cells during Genetically Determined and Secondary Arterial Hypertension

Bulletin of Experimental Biology and Medicine, 2012

Activities of caspase-3 and caspase-8 in the left ventricular myocardium of Chinchilla rabbits wi... more Activities of caspase-3 and caspase-8 in the left ventricular myocardium of Chinchilla rabbits with renovascular arterial hypertension and spontaneously hypertensive rats were measured after 10-day administration of a macroergic compound phosphocreatine. Treatment with phosphocreatine prevented activation of caspase-3, but had no effect on caspase-8 during secondary and genetically determined arterial hypertension. Our results indicate that the intrinsic mechanism of the induction of the caspase cascade in myocardial cells dominates over the extrinsic pathway during both types of arterial hypertension. Energy defi cit is one of the inducing factors of these processes.

Research paper thumbnail of Activities of Some Caspase Cascade Enzymes and Myocardial Contractility in Experimental Left Ventricular Focal Ischemia

Bulletin of Experimental Biology and Medicine, 2011

Focal left ventricular ischemia was modeled in male Chinchilla rabbits. Activities of caspase-3 a... more Focal left ventricular ischemia was modeled in male Chinchilla rabbits. Activities of caspase-3 and caspase-8 in the left and right ventricular myocardium and myocardial contractility were studied after 1, 3, and 5 days. Caspase-3 activity increased signifi cantly in the left ventricular
peri-infarction zone and right ventricular myocardium, while caspase-8 activity did not differ from the control. Left ventricular contractility decreased signifi cantly and the hemodynamic load of the right ventricle sharply increased. These results attest to induction of the internal
(mitochondrial) pathway of apoptosis in myocardial cells most likely caused by left ventricular hypoxia and right ventricular overload.

Research paper thumbnail of Daytime Exposure to Blue Light Alters Cardiovascular Circadian Rhythms, Electrolyte Excretion and Melatonin Production

Pathopysiology, 2022

Artificial light is characterized by certain features of its impact on the body in terms of its s... more Artificial light is characterized by certain features of its impact on the body in terms of
its spectral distribution of power, duration of exposure and intensity. Short waves, perceived as
blue light, are the strongest synchronizing agent for the circadian system. In the present work, we
investigated the features of the circadian rhythms of blood pressure (BP), heart rate (HR), the excretion
of electrolytes and the secretion of melatonin in normotensive (Wistar–Kyoto) and hypertensive
(SHR) rats under the action of monochromatic blue light in the daytime period. It was found that
the exposure of Wistar–Kyoto rats to monochromatic blue light was accompanied by a significant
decrease in nighttime and 24 h systolic BP. The most remarkable changes are characteristic of the
HR in SHR rats under monochromatic light. A significant decrease in HR in each time period was
found, but the predominance of nighttime over daytime values remained in SHR animals. There
was also a significant increase in the mesor of the HR in SHR rats. Additionally, the amplitude of
diastolic BP and HR, as well as the range of oscillations in HR, were significantly increased compared
with the standard light pattern. In contrast to SHR rats, the regulation of the circadian rhythms
in Wistar–Kyoto rats was more flexible and presented more changes, which may be aimed at the
adaptation of the body to environmental conditions. For Wistar–Kyoto rats, an increase in the level of
excreted electrolytes was observed under the action of monochromatic light, but no similar changes
were found in SHR rats. For Wistar–Kyoto rats, a significant decrease in the urine concentration of
aMT6s in the daytime and nighttime periods is characteristic, which results in the loss of the circadian
rhythm. In SHR rats, there was a significant decrease in the nighttime content of aMT6s in the urine,
while the daytime concentration, on the contrary, increased. The obtained data demonstrate that
prolonged exposure to monochromatic blue light in the daytime period affects the circadian structure
of the rhythms of the cardiovascular system, the rhythm of electrolyte excretion and the production
of epiphyseal melatonin in wild-type and hypertensive animals. In SHR rats, the rhythms of BP and
HR exhibit a more rigid pattern.

Research paper thumbnail of The effect of bright light on blood pressure and heart rate in essential hypertension

Research paper thumbnail of Limitations of Seasonal Pattern Assessment Questionnaire and Development of Shastun's Questionnaire for Assessment of Seasonal Affective Disorders, Among Namibian Students in Moscow

Background. The environmental transition from one country to another after migration may be also ... more Background. The environmental transition from one country to another after migration may be also associated with change in seasons, weather and climate as well as in psychosocial stress which may put a greater demand on physiology and metabolism of migrants that may predispose to cardiometabolic risk. This is commonly seen among students of the People's Friendship University of Russia. Moscow. This study examines the validity of the newly developed questionnaire by Dr Shastun, for assessment of seasonal affective disorder (SAD) among students of Namibia studying at Moscow. Subjects and Methods. After approval by the Review board/ethics committee of Faculty of Medicine, People's Friendship University of Russia, Moscow and written informed consent, subjects were recruited for this study. The study involved; Namibian students migrating to Russia while studying in Moscow. Of 87 students from Namibia, all of them volunteered to participate in the study. Seasonal affective disorder (SAD) was studied by Shastun's questionnaire and Seasonal Pattern Assessment Questionnaire (SPAQ). The SPAQ is a brief, self-administered screening tool for seasonal affective disorder (SAD) which may have limitations. The criterion for diagnosis of SAD was a score of 11 or higher on this scale which means the highest level of SAD. The diagnosis SAD was also made by administering Shastun's questionnaire. Results. The results indicate that clinical manifestations indicating SAD were rare while the students were in Namibia, which showed significant increase after migration to Russia and staying minimum for one year. Hypersomnia, overeating and carbohydrate craving were common manifestations of SAD. The prevalence of SAD by Shastun's questionnaire was significantly lower compared to frequency of SAD by SPAQ, respectively (11.9% vs. 18.5%, P ≤ 0.05). The number of sunny days per year and the average annual temperature of the region of stay appear to be the most significant confounders and for the occurrence of cardiometabolic risks among students.

Research paper thumbnail of Effect of Phosphocreatine and Ethylmethylhydroxypyridine Succinate on the Expression of Bax and Bcl-2 Proteins in Left-Ventricular Cardiomyocytes of Spontaneously Hypertensive Rats

We studied the effect of phosphocreatine and ethylmethylhydroxypyridine succinate on the expressi... more We studied the effect of phosphocreatine and ethylmethylhydroxypyridine succinate on the expression of Bax and Bcl-2 proteins in left-ventricular cardiomyocytes of spontaneously hypertensive rats (SHR). Both drugs have no effect on the expression of Bcl-2, but significantly reduce the level of Bax protein (phosphocreatine produces more pronounced effect). These data attest to an important role of energy defi cit and oxidative stress in the induction of cardiomyocyte apoptosis in genetically determined arterial hypertension.

Research paper thumbnail of Specific Features of Electrolyte Excretion at the Early Stages of Arterial Hypertension in SHR Rats

Daytime and nighttime systolic and diastolic BP was recorded in 23-week-old SHR and Wistar rats b... more Daytime and nighttime systolic and diastolic BP was recorded in 23-week-old SHR and Wistar rats by telemetric monitoring. Urine concentrations of sodium, potassium, and calcium were determined in SHR rats during of light (07.00-19.00 h) and dark hours (19.00-07.00 h) at the age of 18, 19, 20, 21, 22, and 23 week; 23-week-old Wistar rats were used as the control. At early stages of the experiment, urine sodium concentration was elevated in SHR rats both at daytime and at night. Thereafter, this value declined and by 22-23 week was significantly lower than in normotensive Wistar rats, but only during daytime. Daytime potassium concentration significantly surpassed the control level during weeks 18-19 of the experiment, but later, a tendency to a decrease in this parameter was observed. Daytime calcium content in SHR rats did not significantly differ from the control throughout the experiment. At night, this value exceeded the control level by more than 2 times during weeks 18-19, but then returned to the level observed in normotensive animals.

Research paper thumbnail of Influence of geomagnetic activity and earth weather changes on heart rate and blood pressure in young and healthy population

International Journal of Biometeorology, 2017

There are many references in the literature related to connection between the space weather and t... more There are many references in the literature related to connection between the space weather and the state of human organism. The search of external factors influence on humans is a multi-factor problem and it is well known that humans have a meteo-sensitivity. A direct problem of finding the earth weather conditions, under which the space weather manifests itself most strongly, is discussed in the present work for the first time in the helio-biology. From a formal point of view, this problem requires identification of subset (magnetobiotropic region) in three-dimensional earth's weather parameters such as pressure, temperature, and humidity, corresponding to the days when the human body is the most sensitive to changes in the geomagnetic field variations and when it reacts by statistically significant increase (or decrease) of a particular physiological parameter. This formulation defines the optimization of the problem, and the solution of the latter is not possible without the involvement of powerful metaheuristic methods of searching. Using the algorithm of differential evolution, we prove the existence of magnetobiotropic regions in the earth's weather parameters, which exhibit magneto-sensitivity of systolic, diastolic blood pressure, and heart rate of healthy young subjects for three weather areas (combinations of atmospheric temperature, pressure , and humidity). The maximum value of the correlation confidence for the measurements attributable to the days of the weather conditions that fall into each of three magnetobiotropic areas is an order of 0.006, that is almost 10 times less than the confidence, equal to 0.05, accepted in many helio-biological researches.

Research paper thumbnail of Cardiomyocyte BECN1-dependent autophagy in acute overload of the left ventricle

FEBS Journal, 2017

Hemodynamic overload of the left ventricle of the heart is accompanied by activation of some mech... more Hemodynamic overload of the left ventricle of the heart is accompanied by activation of some mechanisms responsible for regulated cell death including apoptosis. In the recent years there has been an increasing interest to cardiomyocyte autophagy, which may be a phenomenon involved in programmed (or
regulated) death in some cases, but might also have reparative potential in other circumstances providing cell survival at the expense of its internal resource mobilization. In this work BECN1-dependent cardiomyocyte autophagy was evaluated by the content of Beclin 1 (BECN1) in cardiomyocytes without morphological
evidence of plasma membrane damage in rabbit left ventricular myocardium on 1, 3 and 5 days of acute hemodynamic overload caused by narrowing of the ascending aorta by 1/3 of its initial diameter. Activity of cardiomyocyte autophagy was assessed on the basis of BECN1 content estimation immunochemically
with the use of primary goat polyclonal antibodies (SantaCruzBiotechnology, Inc., USA). It was shown that the
content of BECN1 was rather low in the control group (2.77 vol.%) and significantly decreased (0.54 vol.%) on day 1 after the onset of cardiac overload compared with the controls. On day 3 there was a further decrease in BECN1 in cardiomyocytes (0.20 vol.%). On day 5 this index negligibly increased (0.38 vol.%), but still remained significantly lower in comparison with controls. It was also found that intensity of positive stain was
much higher in the myocardial sites with denser vascular tree. It might be suggested that cardiomyocyte autophagy is a mechanism of cell resource mobilization in the intact myocardium rather than regulated cell death. Its inhibition under acute cardiac overload is most probably due to a severe energy deficit. The publication was financially supported by the Ministry of Education and Science of the Russian Federation (the Agreement No.02.A03.21.0008).

Research paper thumbnail of The polyamine exchange modulating compounds as anticancer agents

FEBS Journal, 2017

A deviation in polyamine (PA) metabolism is observed in various tumors in comparison with normal ... more A deviation in polyamine (PA) metabolism is observed in various tumors in comparison with normal tissues. In this regard, the PA exchange is considered as a target for the drug design of potential anti-tumor agents. The compounds activating PA catabolism are supposed to cause production of cytotoxic PA-metabolites
such as H2O2, acrolein, NH3 and thus to be potential anticancer agents. We suggest 3 main criteria for the primarily selection of PA-exchange modulating compounds. They must inhibit or at least not activate PA biosynthesis, activate PA catabolism, and show good membrane permeability. We have tested 30 different
compounds. The ODC and PAO activities were measured according to the standard PA protocols. The membrane permeability was evaluated through a standard PAMPA procedure. Cell growth inhibition was tested in a modified MTT-test in such cancer cell lines as PC3, MCF-7, MEL-7. Correlations between the
cytotoxic activity and membrane permeability were shown in different groups of compounds for all cell lines with the highest one for MEL-7. A correlation between the cytotoxic activity and spermine oxidation was shown in the group of copper complexes for MCF-7. The most cytotoxic was copper complex with the fluoroaniline derivative. Its IC50 was found to be in the range of 000,1 M. It showed PA biosynthesis inhibition, PA oxidation activation and good permeability as well. As the antiproliferative effect is supposed to be mediated by PA themselves being thesource of cytotoxic agents, the cell sensitivity is expected to be
PA level-dependent. However PC3 cells were the most sensitive to these compounds, although their initial PA levels are lower than those in MCF-7 cells. Further investigations are necessary for this group of compounds to justify it as potential anticancer agents. The publication was financially supported by the Ministry of
Education and Science of the Russian Federation (the Agreement No.02.A03.21.0008).

Research paper thumbnail of Distribution of the EDNRA H323H polymorphic genetic marker of cardiovascular diseases among populations of Syria, and Central Russia

FEBS Journal, 2017

Endotheline-1 is a potent vasoconstrictor that exerts this effect through ETA receptors; much evi... more Endotheline-1 is a potent vasoconstrictor that exerts this effect through ETA receptors; much evidence suggests that genetic variations in the EDNRA gene encoding ETA receptors may play a role in the pathogenesis of many cardiovascular diseases. The ethnic characteristics of the distribution of the EDNRA gene polymorphism may influence the development of these disorders in different populations; therefore we investigated for the first time the distribution of the synonymous polymorphism H323H (T>C) of the EDNRA gene (rs5333) among 50 Arab Syrians with the mean age of 26.19 � 8.03 years and 59 Russians from Central
Russia (19.67 � 1.96). The genotypes were determined with the use of PCR-RFLP (restriction fragment length polymorphism). The C allele frequency of the H323H polymorphism in Syrians and Russians was 27% and 8%, respectively. The genotype frequencies were in Hardy-Weinberg equilibrium in both populations (P > 0.05). The TT, TC and CC genotype frequencies were 58%, 30% and 12% among Syrians and 84.75%, 15.25%, 0% in the Russian population, respectively. A significant difference was found in the H323H genotype distribution
between Russians and Syrians (P = 0.011), as well as in allelic distribution (X2 = 11.22; P = 0.0008). These results show that the distribution of the H323H EDNRA polymorphism among Syrians and Russians should be investigated in larger samples, and considered in the further study of genes associated with cardiovascular
diseases. The publication was financially supported by the Ministry of Education and Science of the Russian Federation (the Agreement No.02.A03.21.0008).

Research paper thumbnail of Comparative study of the biocompatibility of polydioxanone and polyglycolide absorbable meshes for hernia and pelvic defects repair

FEBS Journal, 2017

The recurrence frequency of tension-free hernia repair with synthetic unresorbable and resorbable... more The recurrence frequency of tension-free hernia repair with synthetic unresorbable and resorbable mesh-implants compared to plastic surgery by own tissues decreased from 54% to 16%, but the frequency of mesh-related complications achieved 32%. By now there is no ideal prosthesis, so the development of a fully absorbable synthetic mesh implant is an effective way to solvethis problem. The aim of the study was to assess the biocompatibilityof polydioxanone (PDO) and polyglycolide (PGA) mesh implants. In vitro evaluation of cytotoxicity of mesh materials was performed by MTT assay. Evaluation of in vivo
biocompatibility of meshes was carried out on rat full-layer abdominal wall defect model. On day 3, 10, 30 and 60 after surgery tissues were collected for macroscopic, tensiometric, morphometric, immunohistochemical and western blot studies. MTT assay showed that both meshes did not possess cytotoxic properties.
In vivo experiment showed significant difference in adhesion intensity between the groups: PDO caused less adhesion score on day 3, 30, and 60. The resorption rate also differed: PGA filament area reduced by 36.5 � 4.7% vs 17.4 � 2.3% for PDO filament area. Maximal capsule thickness was observed in PGA on day 10 and 30 after the surgery, while PDO and Permacol capsules were thinner and almost didn’t change throughout the
whole experiment. PDO, PGA and Permacol meshes induced complex differences in the type of FBR over the time course of implantation. PDO evoked a milder early inflammatory response than other meshes. Significantly higher number of FBGC and Langhans cells were apparent throughout the time course in
PGA group. PDO led to better tissue integration and new collagen deposition compare to PGA. PDO provided better vascularization compared to Permacol. PDO mesh has higher biocompatibility than PGA mesh or even Permacol. The publication was financially supported by the Ministry of Education and Science of the Russian Federation (the Agreement No.02.A03.21.0008)

Research paper thumbnail of Melatonin Production in Essential Hypertension Under Common and Modified Light Schedules

Neuropsychobiology: 29-th Annual Meeting of the Society for Light Treatment and Biological Rhythms, 2016

Objectives: According to numerous data, the pathogenesis of cardiovascular diseases is associated... more Objectives: According to numerous data, the pathogenesis of cardiovascular diseases is associated with desynchronization of biological rhythms. Nowadays many people are exposed to excessive light at night which results in the inhibition of melatonin secretion by the pineal gland. In this study we explored the biosyn-thesis of epiphyseal melatonin under extended light exposure in essential hypertension. Methods: Experiments were carried out on male rats of SHR (hypertensive) and Wistar (normotensive) strains. Two different light-dark schedules were modeled: 12 hour light / 12 hour darkness with light on at 7.00 a.m. and off at 7 p.m. (12:12) and 16 hour light / 8 hour darkness with light on at 5.00 a.m. and off at 9.00 p.m. (16:8). Wistar rats were kept under 12:12 light-dark schedule, SHR rats were exposed to both 12:12 and 16:8 schedules. Melato-nin production was assessed by measuring urinary concentrations of its stable metabolite – 6-Sulfatoxymelatonin (6-SMT). Urine collection was performed in metabolic cages twice for 24 hour period – during the daytime and nighttime. It is well known that uri-nary concentration of 6-SMT correlates with the total melatonin blood level [Griefahn et al., 2001; Rapoport S.I. et al., 2009]. Concentration of 6-SMT in animal urine was determined using ELISA kit for 6-Sulfatoxymelatonin (Buhlmann Laboratories AG, Swit-zerland). Results: It was found that daytime urinary concentration of 6-SMT was significantly lower in comparison with the nighttime values in hypertensive rats exposed to both 12:12 and 16:8 light-dark schedules. Daytime 6-SMT concentration was 25.5 ± 1.49 ng/ ml in normotensive Wistar rats and it was significantly decreased to 16.27 ± 1.23 and 14.55 ± 1.32 ng/ml in SHR hypertensive rats kept under 12:12 and 16:8 light-dark schedules respectively. There was also an increase in the difference between day and night 6-SOMT in hypertensive rats kept under both light-dark regimens compared with controls. Meanwhile no difference in daytime 6-SMT urine contents was seen under light regimen 12:12 in comparison with 16:8 between the two groups of SHR rats. As regards nighttime, the values of urinary 6-SMT in Wistar rats, SHR rats under 12:12 and 16:8 light-dark regimens were as follows: 32.74 ± 2.78, 30.37 ± 2.54 and 26.08 ± 2.35 ng/ml with no significant differences between animal groups. Conclusions: The study results suggest the rate of daytime epiphyseal melatonin production is markedly lower under increased blood pressure. There was no significant effect of extending light exposure from 12 to 16 hours within the 24 hour period on melatonin biosynthesis by the pineal gland in essential hyper-tension.

Research paper thumbnail of Element Status of Students with Different Levels of Adaptation

Bulletin of Experimental Biology and Medicine, 2017

The element status was studied in students with different levels of adaptation determined by the ... more The element status was studied in students with different levels of adaptation determined by the parameters of cardiointervalography. The content of chemical elements in the hair was measured by atomic emission and mass spectrometry. In students whose autonomic status was characterized by sympathicotonia, the level of cobalt in the hair was significantly higher, while the levels of manganese and magnesium were lower than normal. The content of selenium in the hair was 2.3 times lower in the study group in comparison with the median level in Russia. The content of toxic elements did not exceed the normal. Significant positive correlations between hair content of magnesium and calcium and between potassium and sodium were revealed.

Research paper thumbnail of Characteristics of General Pathological Processes in the Lungs Following Clozapine Poisoning Experimental Studies

Obshchaya Reanimatologiya, 2017

The aim of the study: to study general pathological processes in the lungs in different time afte... more The aim of the study: to study general pathological processes in the lungs in different time after acute clozap
ine and combined clozapine+ethanol poisonings. Materials and methods. The experiments were performed on 25 outbreed male rats. The animals were divided into 5 groups: 1) reference (intact rats); 2) clozapine poisoning, 3 hours; 3) clozapine poisoning, 24 hours; 4) combined clozapine and ethanol poisoning, 3 hours; 5) combined clozapine and ethanol poisoning, 24 hours. Clozapine
was administered orally at a dosage of 150 milligrams per kilogram of the animal weight under anesthesia (chlorolase); alcohol was administered with clozapine orally at a dosage of 5 milliliters per kilogram of the animal weight. Animals of all these groups sacrificed by decapitation. Lung tissue samples were examined by light microscopy using a microscope Nikon Eclipse E%400 with a video system based on camera Watec 221S (Japan) at a 400x magnification. We evaluated the presence of the following signs: circulatory disturbances (hyperemia, hemorrhage), presence of atelectasis and dystelectasis, emphysema, cellular response (increased white blood cells count), desquamation of epithelium into the lumen of the bronchi, sludge. A morphometric analysis was performed using a grid developed by G. G. Avtandilov. The following signs were evaluated (volume percent, vol.): the area of the alveoli, intraalveolar septi, vessels, white blood cells, the percentage of white blood cells in the intraalveolar septi , the area of the edema and dystelectasis. Results. the following histologic signs were found 3 hours after clozapine poisoning: desquamation of epithelium into the lumen of the bronchi; cellular response (increased white blood cells count); presence of atelectasis and dystelectasis; thickening of intraaveolar septi due to edema; infiltration of intraalveolar septi by WBCs. Atelectasis and dystelectasis in ulmonary parenchyma and infiltration with WBC were observed 24 hours after clozapine poisoning. In the group of animals treated with ethanol and clozapine and decapitated 3 hours after the poisoning the following histological signs were detected: desquamation of epithelium into the lumen of the bronchi, the secret in the lumen of the bronchi, cellular response, atelectasis and dystelectasis, perivenular hemorrhages, hemorrhages into the alveoli, hemorrhages into intraalveolar septi, dilation of the lumen of the bronchi, the presence of sludge, thickening of intraalveolar septi (due to infiltration with WBCs, detachment of the endothelium in blood vessels. Arterial hyperemia, cellular response (increased of WBC count), atelectasis and dystelectasis, and thickening of intraalveolar septi were found 24 hours after combined ethanol and clozapine poisoning. In all study groups the lumen of the alveoli was significantly smaller as compared to the reference group, but the area of the intraalveolar tissue, on the contrary, was significantly greater. The total area of pulmonary microvessels did not differ significantly from the reference group 3 hours after clozapine poisoning. It became significantly higher 24 hours after the poisoning. A significant increase in this parameter vs. the reference group was found both 3 and 24 hours after the administration of the combination of clozapine with ethanol by animals. Conclusion. In clozapine and clozapine + ethanol poisoning, a certain complex of general pathological processes in lungs develops. There are alteration of bronchial epithelium and the vascular endothelium, circulatory disorder, increased vascular permeability, infiltration of intraaveolar septis. Morphological and immunoreactive changes can be used for valuation of severity of general pathological process in acute clozapine and clozapine + ethanol poisonings and determination of the exact time of the poisonings.

Research paper thumbnail of Cardiomyocyte Autophagia and Morphological Alterations in the Left Ventricular Myocardium during Acute Focal Ischemia

Bulletin of Experimental Biology and Medicine, 2016

In experiments on rabbits we evaluated the intensity of cardiomyocyte autophagia by the level bec... more In experiments on rabbits we evaluated the intensity of cardiomyocyte autophagia by the level beclin-1 protein and morphology of the left ventricular myocardium on days 1, 3, and 5 after the onset of focal ischemia caused by ligation of the descending branch of the left coronary artery. The morphological alterations in the left ventricular myocardium were accompanied by intensifi cation of cardiomyocyte autophagia, which attained maximum on postligation day 1.

Research paper thumbnail of Expression of Bax Protein and Morphological Changes in the Myocardium in Experimental Acute Pressure Overload of the Left Ventricle

Bulletin of Experimental Biology and Medicine, 2016

The expression of Bax protein, marker of intracellular pathway of apoptosis initiation, in viable... more The expression of Bax protein, marker of intracellular pathway of apoptosis initiation, in viable left ventricular cardiomyocytes and morphological changes in the myocardium in acute pressure overload of the left ventricle were studied in experiment on male rabbits. The content of Bax protein in the cardiomyocyte cytoplasm decreased, this indicating that the mitochon-drial pathway was not involved in the realization of the apoptotic program. This decrease was associated with manifest destructive changes in the left ventricular myocardium.

Research paper thumbnail of Features of the Structure of the Circadian Rhythm of Blood Pressure and Heart Rate under Genetically Determined Hypertension in the Experiment

Bulletin of Experimental Biology and Medicine, 2015

In SHR rats of different ages (22, 26, 30, 34, and 38 weeks), continuous 24-h telemetric monitori... more In SHR rats of different ages (22, 26, 30, 34, and 38 weeks), continuous 24-h telemetric monitoring of BP and HR was performed. The amplitude and power of oscillations of diastolic BP signifi cantly decreased at the later stages of arterial hypertension (38 weeks), which was considered as a poor prognostic marker. We also observed a signifi cant decrease in the mean daytime, nighttime, and maximum HR and mesor on weeks 30 and 34, but not on week 38, which can refl ect triggering of the adaptive response followed by its exhaustion.

Research paper thumbnail of Effect of Phosphocreatine and Ethylmethylhydroxypyridine Succinate on the Expression of Bax and Bcl-2 Proteins in Left-Ventricular Cardiomyocytes of Spontaneously Hypertensive Rats

Bulletin of Experimental Biology and Medicine, 2015

We studied the effect of phosphocreatine and ethylmethylhydroxypyridine succinate on the expressi... more We studied the effect of phosphocreatine and ethylmethylhydroxypyridine succinate on the expression of Bax and Bcl-2 proteins in left-ventricular cardiomyocytes of spontaneously hypertensive rats (SHR). Both drugs have no effect on the expression of Bcl-2, but significantly reduce the level of Bax protein (phosphocreatine produces more pronounced effect). These data attest to an important role of energy defi cit and oxidative stress in the induction of cardiomyocyte apoptosis in genetically determined arterial hypertension.

Research paper thumbnail of Characteristics of Circadian Rhythm of Blood Pressure during Long-Term Hypertension Development in SHR Rats

Bulletin of Experimental Biology and Medicine, 2013

The specifi c features of circadian rhythm of BP were investigated in freely moving male SHR rats... more The specifi c features of circadian rhythm of BP were investigated in freely moving male SHR rats using telemetry monitoring technique. BP was recorded in the abdominal aorta according to 24-h/4-month schedule. The data were obtained from 22, 26, 30, 34, and 38-week-old animals. Normotensive Wistar rats (22 weeks) served as the control. It was found that the mean 24-h, daytime, and nighttime systolic and diastolic BP in hypertensive rats signifi cantly surpassed the control throughout the observation period and practically did not change during prolonged hypertension. Some prognostically negative changes in the circadian rhythm of the basic hemodynamics system parameters appeared with time. For instance, the maximum 24-h systolic BP signifi cantly increased in comparison with the initial level.

Research paper thumbnail of Energy Deficit as a Possible Factor for the Induction of Caspase-Dependent Apoptosis in Left Ventricular Myocardial Cells during Genetically Determined and Secondary Arterial Hypertension

Bulletin of Experimental Biology and Medicine, 2012

Activities of caspase-3 and caspase-8 in the left ventricular myocardium of Chinchilla rabbits wi... more Activities of caspase-3 and caspase-8 in the left ventricular myocardium of Chinchilla rabbits with renovascular arterial hypertension and spontaneously hypertensive rats were measured after 10-day administration of a macroergic compound phosphocreatine. Treatment with phosphocreatine prevented activation of caspase-3, but had no effect on caspase-8 during secondary and genetically determined arterial hypertension. Our results indicate that the intrinsic mechanism of the induction of the caspase cascade in myocardial cells dominates over the extrinsic pathway during both types of arterial hypertension. Energy defi cit is one of the inducing factors of these processes.

Research paper thumbnail of Activities of Some Caspase Cascade Enzymes and Myocardial Contractility in Experimental Left Ventricular Focal Ischemia

Bulletin of Experimental Biology and Medicine, 2011

Focal left ventricular ischemia was modeled in male Chinchilla rabbits. Activities of caspase-3 a... more Focal left ventricular ischemia was modeled in male Chinchilla rabbits. Activities of caspase-3 and caspase-8 in the left and right ventricular myocardium and myocardial contractility were studied after 1, 3, and 5 days. Caspase-3 activity increased signifi cantly in the left ventricular
peri-infarction zone and right ventricular myocardium, while caspase-8 activity did not differ from the control. Left ventricular contractility decreased signifi cantly and the hemodynamic load of the right ventricle sharply increased. These results attest to induction of the internal
(mitochondrial) pathway of apoptosis in myocardial cells most likely caused by left ventricular hypoxia and right ventricular overload.