The aim is to study the prognostic potential of the parameters of the pulmonary function tests parameters in determining the risks of developing comorbid pathology. Material and methods. The study included 102 people, with an average age of 47 [43-52.7] years. Questionnaires, anthropometry, blood sampling for biochemical analysis, and spirometry were conducted. Cardiovascular risk (CVR) was calculated on the SCORE2 scale, stratification of the subjects by risk groups was carried out in accordance with the gradation on the scale used. Statistical processing was performed using nonparametric methods. Results. According to the calculation of the SSR on the SCORE2 scale, all the subjects were in the range of moderate (58.7 %) and high risk (41.3 %). The obtained data from the study of the respiratory function of the general sample were slightly lower in women than in men, with significant differences in the obtained FVC, FEV1, FEF2575. Depending on the presence of arterial hypertension (AH) it was found that the median values of both the actual and calculated lower limits of the norm (LLN) of spirometry indicators among people with AH were lower than those studied without hypertension. At the same time, significant differences depending on the presence of AH were revealed only in the case of LLN for FEV1, FEV1/FVC, FEF2575. In individuals with hypertension, the LLN-FEV1/FVC index was significantly lower than 70 %. In the group of subjects with hypertension, an inverse reliable relationship was found (p = −0.4; p < 0.001) between LLN-FEV1/FVC and the level of uricemia – a decrease in the index by 0.008 % will lead to an increase in uric acid by 1 mmol/l. A decrease in LLN-FEV1/FVC by 0.2 l and LLN-FEF2575 by 0.03 l/sec will increase the CVR on the SCORE2 scale by 1 % ((p = −0.5; p < 0.001) (p=−0.3; p=0.002), respectively). Conclusion. An assessment of the prognostic potential of the pulmonary function tests parameters in determining the risks of comorbid pathology, namely a combination of cardiovascular diseases and respiratory pathology, was carried out. A combined approach to the examination of the able-bodied population, taking into account spirometry data, will help to personify and in-depth assess the risks of developing significant diseases that affect the quality and life expectancy of the patient, his ability to work.

Cardiovascular diseases take a leading position in the structure of mortality in modern society. Most diseases are characterized by uncontrolled processes of oxidative stress, proteolysis, tissue and cellular hypoxia, which cause endothelial dysfunction. Tissue and cellular hypoxia accumulated with mitochondrial reactive forms of oxygen damaging lipoproteins, proteins, nucleic acids plays an important role in the pathogenesis of vascular aging. Cellular aging is characterized by a decrease in the number of mitochondria, a decrease in the number of copies of mitochondrial DNA, and the loss of mitochondrial protein. In addition to morphological changes, the function of mitochondria is oppressed, at the same time the activity of their proteins and enzymes decreases. Changes in the functions of mitochondria can be secondary in response to various stimuli and are associated with a violation of their structure and a change in activity in response to specific genetic and phenotypic conditions. Reprogramming of mitochondrial biogenesis occupies a central position in the theory of cellular aging and is one of the targets for interventions in prolonging active longevity.

Objective: to assess cerebral blood flow and reveal early myocardial remodeling in COPD patients with varying degrees of airflow restriction. Materials and methods: the research included 105 patients with COPD from 1 to 4 degrees of severity, depending on the degree of restriction of FEV1 without CVD, diabetes mellitus, chronic kidney disease, obesity, other systemic and oncological diseases. Average age was 57.12 ± 0.68 years, men 45%. 5 groups were identified: mild severity of COPD (GOLD1, = 24), moderate (COLD2, n = 39), severe (GOLD3, n = 30), very severe (GOLD4, n = 12). Control group (n = 37) was tobacco free and CVD. Blood pressure and ultrasound tracranial dopplerography were performed in all groups. Transtoral echocardiography with assessment of global and local LV longitudinal deformation by the strain method and determination of left ventricular diastolic dysfunction (DDLV) was performed in GOLD1 and GOLD2 groups. Parameters of average values of deformation in basal, medial and apical segments are evaluated. Results were processed with Microsoft Excel 2016 and STATISTICA 10 (StatSoft, Inc., USA). Results: arterial hypertension (AH) was detected in 56.4% of patients in the COLD2 group; 56.7% of patients in the GOLD3 group and 100% of patients in the GOLD4. Сhanges in cerebral blood flow were not found in the GOLD1-3 groups. Significant increase of linear blood flow rate of middle cerebral arteries and index of peripheral vascular resistance were detected in group GOLD4 relative to control and GOLD1-3 groups (p < 0.05). DDLV of 1 type was revealed in 27.7% of patients of COPD and was higher at patients with COPD and AH - 62.5% (χ²=11.5, р =0.009). Pathological patterns were identified at the level of the basal and medial parts of the left ventricle in patients with COPD. Conclusion: preclinical signs of target organ involvement identified in COPD patients without cardiovascular disease. Changes in cerebral blood flow in the form of an increase in linear blood flow rate and peripheral vascular resistance index were detected in the GOLD4 group. DDLV of 1 type was detected in the GOLD1-2 groups and was found more frequently in the combination of COPD with AH. Pathological patterns were identified at the basal and medial left ventricular levels in a combination of COPD and AH. Changes in target organs indicate the need for an in-depth search to reclassify cardiovascular risk and identify an individual prevention plan.

Chronic tobacco smoking (CTS) is an important risk factor of endothelial dysfunction (ED) development, one of the common pathogenetic mechanisms for COPD and arterial hypertension (AH). We are considering the role of hypoxia and Hypoxia-Inducible Factor-1α (HIF-1α) in the development of ED and the formation of adaptation mechanisms in CTS. The aim of the study is to analysis the state of HIF-1α in capillaries and neurons of the brain of rats with a COPD model which induced by CTS. Material and methods: we examined 30 Wistar rats divided into 2 groups. In the 1st group (n = 20), a COPD model was created by the CTS method during 6 months. The 2d control group included 10 rats breathed atmosphere air. After experiment ended, we measured blood pressure and studied relative density of HIF-1α-positive neurons and capillaries in the parietal cortex immunohistochemically. Results: 90% of animals in the 1st group demonstrated a blood pressure increase in compared to the 2d group (BP/control – 126,2±5,1 and 82,3±3,8 mmHg.; BP/COPD – 145,5±5,9 and 92,6±4,1 mmHg., p <0,05). HIF-1α marker at control group rats are detected in a small number of pale stained neurons and capillaries. Modeling of COPD revealed that the density of HIF-1α-positive neurons increased to a greater extent (by 18.6%), while the number of HIF-1α-positive capillaries increases by 10.3%. Conclusion: the use of CTS to model COPD leads to the occurrence of AH in 90% of cases. Chronic hypoxia (CH) is one of the unifying factors development of comorbidity in the form of COPD and AH. In the mechanisms of adaptation of the brain in COPD and AH to CH takes part HIF-1α, the level of which increases in neurons and capillaries of the parietal cortex.

This review presents data on the cellular-molecular mechanisms regulating angiogenesis associated with the vascular endothelium. Existing concepts hold that the control of angiogenesis involves activated endothelial cells and their precursors (progenitor cells), which synthesize and release angiogenic molecules with different chemical structures and mechanisms of biological action, but all allowing these cells to control each stage of angiogenesis directly or indirectly. Balanced functioning of the system of molecular stimulators and inhibitors of angiogenesis is particularly important for the brain, as excessive formation of blood vessels, like inadequate development of blood vessels, leads in certain conditions to rapid and irreversible changes in nervous tissue. Post-operative neurorepair cannot occur without adequate reperfusion of the injured part of the brain, which can be supported by timely stimulation of angiogenesis, while intensification of this process in tumors, conversely, has adverse consequences. Tumor growth and metastasis are significantly linked with increases in the level of vascularization of malignant tissue, while blockade of angiogenesis is not infrequently the only productive method of limiting tumor growth. However, we have insufficient knowledge of the mechanisms regulating angiogenesis in the brain at the cellular-molecular level in physiological conditions and pathology, so angiogenic influences do not always produce the expected effect.

We measured the content of HIF-1α and HIF-2α-immunopositive neurons and microvessels in the brain of Wistar rats during the first 24 h of tissue hypoxia induced by subcutaneous injection of cobalt dichloride (50 mg/kg). In control rats (without hypoxia), immunohistochemical marker HIF-2α in cortex of parietal lobe was not detected, and HIF-1α was detected only in few weakly stained pale neurons and capillaries. In 30 min after injection of the cobalt salt, the number of HIF-1α+ neurons increased by 25.6% (in capillaries by 12.3%), many of these were characterized by intensive reaction; the quantitative parameters reached their maximum level within 1-3 h. However, the concentration of immunopositive neurons returned to the control values in 6 h after hypoxia modeling (capillaries in 9 h). In contrast to HIF-1α, the number of neurons and capillaries containing HIF-2α reached a maximum level in 6-12 h of hypoxia. The relative density of HIF-2α+ capillaries increased most pronouncedly (by 23.6%); the relative density of neurons increased by 18.9%. The relative density of HIF-2α+ cells did not change significantly to the end of the experiment. Thus, HIF-1α is more essential for regulation of adaptation to hypoxia in neurons and HIF-2α is more important for the endothelium of microvessels.

AIM To study the distribution of MMP-2 and MMP-9 and their inhibitors (TIMP-2 and TIMP-1 respectively) in the brain vascular bed of rats exposed to chronic tobacco smoke. MATERIAL AND METHODS Localization and expression of MMP-2, MMP-9, TIMP-2 and TIMP-1 in the pial branches (I-V order vessels), intracerebral arteries and capillaries of rats exposed to tobacco smoke were studied for 36 weeks. The level of enzymatic activity was assessed by the relative quantity of enzymopositive arteries and amount of fragments per 1 mm2 and rate of immunohistochemical reaction. Specific capillary density per mm2 of brain tissue and optical density of the immunohistochemical product were calculated. RESULTS MMP-2 and TIMP-2 were found in all segments of the arterial course in control animals. In rats exposed to tobacco smoking, the expression of MMP-2 increased only in intracerebral arteries and capillaries while TIMP-2 level decreased. MMP-9 and TIMP-1 were noted only in single vessels, mainly small pial and intracerebral arteries, in intact animals. In rats exposed to tobacco smoke, MMP-9 expression significantly increased in all segments of the arterial course whereas the increase in TIMP-1 was observed mainly in large pial arteries. CONCLUSION In physiological conditions, the dynamic balance between MMP-2 and TIMP-2 maintains basic tissue metabolism. Products of tobacco combustion are inductors of the inducible MMP-9 which promotes morphofunctional changes. The imbalance in MMP-9 - TIMP-1 system causes the degradation of extracellular matrix in different segments of the brain arterial course promoting the development of cerebral dysfunction.

The capillaries containing MMP-2 and its tissue inhibitor TIMP-2 were examined in cerebral cortex and white matter obtained from intact Wistar rats (n=5) and the rats with progressing experimental renovascular hypertension (n=35). In hypertensive rats, the changes in intensity of the immunohistochemical reaction and in the density of capillaries expressing TIMP-2 significantly differed from the corresponding values in MMP-2-positive capillaries, which resulted in pronounced deviation of MMP-2/TIMP-2 index from the control level (especially in cerebral cortex) probably attesting to enhanced risk of complications in cases with arterial hypertension.

AIM:To study an effect of chronic smoking on cerebral hemodynamics and cerebrovascular reactivity in different segments of the arterial system of the brain in men.MATERIAL AND METHODS:Male patients enrolled in the study were divided into two groups: controls (n=11) and smokers (n=24) with index 30.7 pack-year smoking history. Haemorheological parameters: viscosity of blood, aggregation of erythrocytes, hematocrit, fibrinogen were evaluated in both groups. Using carotid duplex ultrasound (MyLab 50 Esaote, Italy), intima-media thickness (IMT) of common carotid arteries (CCA) was measured. Parameters of cerebral hemodynamics were evaluated using transcranial Doppler ultrasound (Nicolet Companion Biomedikal, USA). Tests of the cerebrovascular reactivity were used to study arteries of three levels: common carotid arteries, middle cerebral arteries (MCA) and pial arteries.RESULTS:An increase in erythrocytes, hemoglobin, hematocrit, viscosity of blood, aggregation of erythrocytes and fibrinogen was found in the group of smokers compared to the control group. There were an increase in IMT of CCA by more than 50% and a decrease in the mean flow velocity in CCA in smokers. Also smoking decreased MCA mean flow velocity, but this decrease was 2-3 times smaller than in the common carotid arteries. Vasoconstrictor reactions prevailed in MCA, as indicated by the increase in the peripheral vascular resistance index. An increase in vasospastic reactions in pial arteries in smokers was discovered. At the same time, the vasodilatation reaction was maintained or not significantly reduced in pial arteries.CONCLUSION:Chronic smoking is one of the significant factors causing changes in haemorheological parameters, damage of vascular wall, initiation of atherogenesis and disturbance of cerebral hemodynamics. The study of velocity characteristics and peripheral vascular resistance indices in the group of smokers revealed different reactions of different segments of the brain arterial system.

1 Институт вышей нервной деятельности и нейрофизиологии РАН (117485, г. Москва, ул. Бутлерова, 5а), 2 Национальный научно-практический центр здоровья детей (119991, г. Москва, Ломоносовский пр-т, 2/1), 3 Институт проблем передачи информации им. А.А. Харкевича РАН (101447, Москва, Большой Каретный пер., 19), 4 Тихоокеанский государственный медицинский университет (690002, г. Владивосток, пр-т Острякова, 2)

Pial arteries of different diameter were studied in intact rats and after 6-month modeling of chronic tobacco smoking in rats. Expression of tachykinin NK1 receptors in pial arteries was studied by biomicroscopy and immunohistochemical methods. Chronic tobacco smoking induced considerable reorganizations of the arterial bed. The intensity of changes depended on the diameter of vessels. In small pial vessels that directly participate in the blood supply to the brain, pronounced vasodilatation and enhanced expression of NK1 receptors in the endothelium mediating the effects of substance P were observed; the number of these vessels also increased. The intensity of the response to tobacco smoke components decreased with increasing vessel diameter.

Изучено состояние сосудистого русла головного мозга и клеток нейроглии в условиях экспериментального моделирования табакокурения. Исследование проведено на 10 крысах-самцах линии Vistar, разделенных на две группы. Контрольная группа животных дышала атмосферным воздухом, а экспериментальную группу ежедневно обкуривали табачным дымом в ингаляционной камере в течение 6 месяцев согласно протоколу H. Zheng и колл. После декапитации животных изготавливались гистологические препараты головного мозга. Срезы головного мозга толщиной 10 мкм окрашивали гематоксилином и эозином, затем оценивали плотность распределения капилляров, удельную плотность распределения клеток глии и индекс Керногана (соотношение толщины стенки артерии к диаметру её просвета). У животных экспериментальной группы установлено достоверное уменьшение количества капилляров в головном мозге. Одновременно с этим отмечается уменьшение числа клеток в веществе мозга, о чем говорит достоверное снижение удельной плотности распределения клеток нейроглии. Эти изменения приводят к повышению сосудистого сопротивления и способствуют структурной перестройке артерий в виде сужения их просвета и утолщения стенки за счёт гипертрофии, о чем свидетельствует увеличенный индекс Керногана в экспериментальной группе.

In this work we developed a new noninvasive index of local segmental electromechanical delay by the simultaneous use of electrical, mechanical and anatomical data obtained from Vector-Electrocardiography (VCG), Speckle Tracking Echocardiography (STE), Computer Tomography (CT) Imaging respectively, in order to provide a better characterization of electromechanical coupling in the left ventricle. This index could be useful to select patients for Cardiac Resynchronization Therapy (CRT) and for the assessment of its effectiveness.

Objective: To characterize the morphology of the brain vessels and glia in experimental modeling of hypertension in rats. Design and method: To create endothelial dysfunction in hypertensive model was reproduced NO deficit in rats in vivo. The animals of the experimental group on a daily basis with the drinking water was administered a NO-synthase blocker as methyl N-nitro-L-arginine (L-NAME, Sigma) for calculating the dose of 50 mg / kg / day. AH development was monitored by measuring the blood pressure of the tail artery at 8 weeks after the administration of L-NAME. (Group 1). The second group consisted of healthy rats that were in standard conditions (group 2). After euthanasia made histological preparations of rat brain, followed by light microscopy - Increase 20. Calculation of results was carried out using Image J. assessed such factors as distribution density of capillaries 1 mm2 (mm/mm), the specific density of the distribution of glial cells. Results: Distribution density of capillaries in the first group was - 32,64 ± 5,1 and 107,01 ± 7,2 in the second. In the first group, a significant decrease in the specific set of cell density neuroglia - 0,62 ± 0,03 as compared with the second group - 4,45 ± 0,05. In the rat model of hypertension microangiopathy showing signs of brain microvascular discharge cells and reduction in the number of neuroglia Conclusions: In the rat model of hypertension microangiopathy showing signs of brain microvascular discharge cells and reduction in the number of neuroglia

Изучено содержание матриксных металлопротеиназ 2 и 9 в условиях экспериментального моделирования табакокурения. Исследование проведено на 10 крысах-самцах линии Vistar, разделенных на две группы. Контрольная группа животных дышала атмосферным воздухом, а экспериментальную группу ежедневно обкуривали табачным дымом в ингаляционной камере в течение 6 месяцев согласно протоколу H. Zheng и колл. После декапитации животных изготавливались гистологические препараты аорты. Исследованы архитектоника стенки аорты и экспрессия матриксной металлопротеиназы-2 (ММP-2) и металлопротеиназы-9 (ММP-9). Для оценки активности данных маркеров использован метод иммунопероксидазной реакции с моно-и поликлональными антителами против MMP-2, МMP-9, также использованы вторичные антитела, меченые пероксидазой хрена. Количественную оценку ферментативной активности определяли, измеряя плотность преципитата гистохимической реакции. У животных экспериментальной группы установлено изменение архитектоники аортальной стенки, а именно утолщение внутренней эластической мембраны, истончение средней оболочки, уменьшении количества рядов гладкомышечных клеток, дезорганизация эластических и коллагеновых волокон. Установлено повышение экспрессии ММР-2 и ММР-9 в интиме и медии аорты, что может являться одним из факторов соединительно-тканного ремоделирования аортальной стенки при табакокурении.

The authors review the literature data and in-house researches on arterial hypertension and smoking-related changes in cerebral vessels clinically and in experiment, and provide the data from transcranial Doppler ultrasound examination, duplex scanning and magnetic-resonance imaging of cerebral vascular bed. As shown, the arterial hypertension and smoking-related cases were characterised by decreased linear blood flow velocity, increased vascular resistance index and more evident cerebral atherosclerosis. The smoking intensity directly correlated with the prevalence of atherosclerotic plaques, including hemodynamically significant stenosis. The authors have identified evident cerebral vasomotor disorders, such as the loss of endothelium-dependent vasodilatation and increase in vasoconstrictive effects.

We studied vasomotor responses of aortic endothelium in a rat model of chronic smoking. It was found that long-term exposure to tobacco smoke (inhalation) impaired vasomotor function of the aortic endothelium leading to insufficient vasodilator activity and enhanced vasoconstriction. After the cessation of inhalations, vasomotor disturbances were not only preserved, but also exacerbated because of increased pathological endothelium-independent vasoconstriction.