Peculiarities of Autonomic Regulation of the Heart in Experimental Normobaric Hypoxia of Different Genesis.

We compared autonomic regulation of the heart in Wistar rats with acute exogenous hypoxic and chronic normobaric hypoxia against the background of experimental chronic obstructive pulmonary disease. In animals subjected to normobaric hypoxia, dysfunction of the autonomic regulation of the heart developed; it manifested in a significant limitation of the effects of the parasympathetic and sympathetic nervous systems on the pacemaker activity of the sinoatrial node. Disturbances in autonomic regulation of the heart in acute exogenous hypoxic normobaric hypoxia were characterized by "rigid" heart rhythm and bradycardia in the presence of systolic-diastolic arterial hypotension. Centralization of heart rhythm control did not provide compensation for hemodynamic disturbances. In case of chronic normobaric hypoxia, an increase in arterial hypoxemia was associated with protective "denervation" of the heart against the background of increased activity of the humoral regulation, which manifested in tachycardia, isolated systolic arterial hypertension, and overstrain of regulatory systems.

Autonomic Cardiac Regulation in Experimental Comorbidity of Chronic Obstructive Pulmonary Disease and Acute Cerebral Ischemia.

Autonomic regulation of the heart was examined in 5 groups of rats: intact, sham-operated, experimental chronic obstructive pulmonary disease, acute cerebral ischemia, and acute cerebral ischemia modeled against the background of chronic obstructive pulmonary disease. The latter was provoked by combination of inhaled papain and intraperitoneal bacterial LPS, whereas acute cerebral ischemia was modeled by single-stage bilateral occlusion of the common carotid arteries. Chronic obstructive pulmonary disease was verified by X-ray computed microtomography. The disturbances in autonomic control of the heart during comorbid pathologies were most prominent; they were manifested by overstrain and decompensation of the mechanisms implicated in the heart control and systolic-diastolic arterial hypotension. The correlations were established between blood oxygenation, respiration rate, and some parameters of autonomic cardiac regulation. The data attest to relevance and usefulness of the developed model of respiratory and cerebrovascular comorbidity in assessment of pathophysiological mechanisms underlying dysregulation of the heart and the development of personalized approaches for its pharmacological correction.

Behavioral and Cognitive Reactions of Rats with Experimental Chronic Obstructive Lung Diseases of Different Degree.

The study presents the results of behavioral phenotyping of rats with experimental chronic obstructive pulmonary disease (eCOPD) of different severity modeled by using a combination of inductors (purified papain and bacterial LPS) in increasing concentrations. Locomotor and exploratory activity, spatial memory, and anxiety were evaluated. In mild eCOPD, locomotor and exploratory activity increased, while other parameters did not differ from the control values. Rats with moderate eCOPD demonstrated moderately restricted locomotor function and increased anxiety. Severe eCOPD was associated with pronounced changes in all analyzed parameters. Correlation analysis revealed relationships between some behavioral parameters and blood oxygen saturation, inspiratory lung volume, and respiration rate. This indicates the role of respiratory failure in the pathogenesis of cognitive disorders.

Assessment of Cardiac Vegetative Control during Acute Graduated Exogenous Normobaric Hypoxia in Rats.

The effects of exogenous normobaric hypoxic hypoxia on vegetative control of the heart and BP were examined in Wistar rats. The reference ranges of variation pulsometry parameters were determined in rats with normoxemia for 3 physiological variants of autonomic homeostasis: eutony, sympathicotony, and vagotony. Most rats (80%) demonstrated autonomic eutony. The study showed that saturation of arterial blood with oxygen is the most adequate assessment of severity of acute exogenous normobaric hypoxic hypoxia progressing within a closed hypoxic chamber, which standardizes this method and minimizes inaccuracies resulting from individual sensitivity to hypoxic stress. The changes in functional activity of systems that control the heart rhythm closely correlated with the drop in arterial blood oxygenation. While a small arterial hypoxemia activated the ergotropic elements of autonomic nervous system central subdivision accompanied by elevation of systolic BP, the moderate hypoxemia augmented the cholinergic influences and moderated the adrenergic ones under maintaining mobilization of the central autonomic nervous system-control loop and normotension. Severe hypoxemia was manifested by augmented influences from autonomic nervous system central subdivisions on the heart rate, disadaptation of the control systems, and systolic-diastolic arterial hypotension.

[Environmental and hygienic aspects of the prevalence of congenital anomalies in Primorskii territory].

The authors have conducted an environmental and hygienic evaluation of the prevalence of congenital anomalies in the Primorye Territory. It has been found that there is a considerable rise in congenital anomalies in children and adolescents, which is predicted for the coming 5 years. The prevalence of congenital anomalies in the region depends on the bioclimatic zone and environmental situation. The highest incidence of the pathology is observed in the children living in the coastal bioclimatic zone and in the adolescents in the critical environmental areas of the continental bioclimatic zone. A combination of sanitary-and-hygienic and natural climatic factors was found to influence the incidence of congenital malformations differently. The sanitary-and-hygienic parameters of an inhabitancy play a leading role (44.5-63.1%).

[Cellular factors of local protection under community acquired pneumonia].

The community acquired pneumonia (CAP) falls into the category of the most frequent human diseases and is one of the leading causes of death from infectious diseases. The main components that characterize the inflammatory process in the lungs at CAP include an increase in vascular permeability, and migration of neutrophils and monocytes/macrophages to the foci of infectious agents inoculation, and the reactivity of these cells defines the upshot of the disease. In the present work, a significant increase in the number of neutrophils and an increase in the number of perishing cells depending on the gravity of current CAP were determined. Herewith, the contents of necrotic neutrophils and macrophages in foci of inflammation dependent on the gravity of current CAP, while the difference between the factors of apoptosis in these patients was not reliable. Apoptotic cell death was mainly revealed in population of macrophages. Analysis of the phagocytic and enzymatic activities of cells of the local defense of CAP patients showed that the state of unspecific resistance of their organisms largely determined the severity of the disease and antibiotic treatment did not affect the normalization of neutrophils and macrophages functions.

[Pathophysiological and therapeutic aspects of bone lesions in patients with multiple myelomas].

Multiple myeloma (MM) is an uncontrolled malignant proliferation of plasma cells. Today, it is the best studied form of hemoblastomas, but many pathophysiological and therapeutic aspects of this condition await a deeper insight. The medico-social significance of the disease is emphasized by its continuous growth, variable clinical manifestations, low quality of the patients" life, mean life expectancy of 3-5 years, and numerous complications. One clinical feature of MM is bone lesions that occur in all patients as osteolysis (OL), osteoporosis (OP), hypercalcemia, and combination of these disorders. Progressive degeneration of bone tissue even in patients responding to chemotherapy results in severe pain, pathological fractures, and neurologic problems. Molecular mechanisms of OL and OP in MM have recently attracted much attention. This review summarizes data on the role of cytokines, growth factors, osteopontin, OPG-RANK-RANK system, macrophage inflammatory proteins, and matrix metalloproteinases in MM-related osteodestruction. Iatrogenic origin of bone lesions is considered. Treatment of MM using thalidomide (lenlalidomide), proteasome inhibitors (bortesamide), and biphosphonates (pamidronate, zoledronic acid) is discussed as the most promising therapeutic strategy promoting plasma cell apoptosis, inhibition of bone resorption, stabilization of osteoblast function, and pain alleviation.

[Immune mechanisms of comorbidity of HIV infection and pulmonary tuberculosis].

AIM: to study the immune system in patients with tuberculosis-associated HIV infection at different stages of disease and during antiretroviral therapy (ARVT). SUBJECTS AND METHODS: The study included 90 patients with tuberculosis-associated HIV infection; a control group comprised 117 HIV-infected patients. The total number of T lymphocytes and their subpopulations (CD3+, CD4+, and CD8+) and the levels of the cytokines TNF-alpha, IL-6, and their soluble receptors SRp55 of TNF-alpha (type I), SRp75 of TNF-alpha (type II), and SR of IL-6 in the serum. RESULTS: T-cell immunodeficiency was detected at all stages of HIV infection accompanied by CD3+ and CD4+ cell deficiency and decreased immunoregulatory index. The cytokine profile changes were indicative of a more noticeable reduction in the functional activity of T helper cells type I in patients with HIV-associated tuberculosis. CONCLUSION: The efficiency of ARVT in patients with HIV-associated tuberculosis was confirmed by a lower viral load and higher CD4+ cells. Heterodirectional changes in the content of cytokines and their receptors characterized by a considerable increase in the levels of TNF-alpha, IL-6, SR of TNF-alpha and a drastic reduction in the level of SR of IL-6 may be considered as a marker of immune recovery.

[Central arterial pressure and importance of its examinations in pulmonology].

Arterial pressure (AP) measured on brachial artery now cannot be considered as an unique marker of vascular tonus. According to literature data, more informative and prognostically valued parameters are central AP (CAP) and indices of arterial rigidity, which closer bound with hypertrophy of vascular wall, intensity of vascular atherosclerotic lesion and occurrence of cardiovascular complications, than peripheral AP and some other classic risk factors. Nevertheless, CAP measuring cannot be considered as alternative to classic method of AP measuring on brachial artery; it only supplements our view of concrete pathological process. Non-invasive CAP measuring at diseases of respiratory organs can be usable for more precise assessment of cardiovascular risk at chronic and acute forms of diseases of pulmonary organs (DPO). The highest risk of CAP increase and cardiovascular complications take place in patients with chronic obstructive pulmonary disease (COPD), aggravation of severe bronchial asthma and in hypertensive patients with pneumonia or aggravation of chronic DPO. Results of CAP measuring can be used as additional diagnostic criteria of stratification of DPO and their complications risk. Early diagnostics of CAP disturbances (aortal hyper- o hypotension) make possible to correct therapy and prevent unfavorable consequences of hemodynamic disturbances. Dynamic control of CAP is reasonable to use for correction of therapeutic programs in departments of intensive care.

[Characteristics of a vasomotor endothelial function of the major and cerebral arteries in bronchial asthma].

We investigated endothelium dependent and independent activity of major and cerebral arteries in mice with experimental bronchial asthma. Regional features of endothelium dependent reactions of arteries were established. It was found that the carotid artery has greater vasomotor activity than the medial cerebral artery. Development of experimental bronchial asthma is associated with sharp reduction of reserve ability for endothelium independent dilatation against intensification of endothelium dependent dilatation; enhancement of constrictor effects of vascular endothelium in major and attenuation in cerebral compartments.

[Interrelation of vasomotor effects in the endothelium of the cerebral and main arteries in obstructive pulmonary diseases].

We have investigated vasomotor activity of the trunk and cerebral arteries in mice with obstructive pulmonary diseases. It was established, that endothelial dysfunction depends on the form of pulmonary disease and has regional vascular features. It was determined, that the maximal disturbances are shown in mice with chronic obstructive pulmonary disease. It express as infringement of regional autonomy vasomotor effects and pathological paradoxical vasoconstriction of cerebral vessels. Bronchial asthma associates with the discordant answer of the brain and trunk arteries with the moderate adaptation of a regional homeostasis.

[Significance of functional tests in investigation of arterial wall rigidity in patients with chronic obstructive pulmonary disease].

The aim of the investigation was to study mechanical properties of the aorta in patients with chronic obstructive pulmonary disease (COPD) using functional tests. 60 patients with COPD and 25 healthy volunteers of comparable age were examined by non-invasive arteriography (Tensio Clinic TL 1 arteriograph, Tensiomed, Hungary) with physical exercise (PE) and nitroglycerin test (NT). Oxygen saturation and the basal serum concentration of nitric oxide were measured. The study found a significant decrease in aortal reactivity after PE in patients with II to III stage COPD vs. healthy persons. The degree of this decrease correlates with the duration and severity of the disease, the degree of ventilatory disturbances, hypoxemia and hyponitrooxidemia. According to non-invasive arteriography, the relative coronary perfusion index during NT was most sensitive to COPD severity when PE test was performed. It was 10 times worse in patients with COPD III vs. healthy persons. The degree of a decrease in the velocity of the spread of pulse wave in the aorta (VSPW) and augmentation index during NT was the same in COPD patients and healthy persons, while in COPD II the sensitivity of these parameters was higher. Study of the mechanic properties of aorta using functional tests substantially complements possibilities provided by conventional arteriography. For instance, some of COPD patients with "optimal" VSPW at rest display a significantly decreased response to PE.

[Central arterial pressure in patients with chronic obstructive pulmonary disease].

AIM: To study central (aortic) arterial pressure (CAP) and aortic stiffness in patients with chronic obstructive pulmonary disease (COPD) of different severity. MATERIAL AND METHODS: Non-invasive arteriography with Tensio Climo TL1 arteriograph (TensioMed, Hungary) was made to measure aortic stiffness and systolic pressure (SAP) in 54 COPD patients and 25 healthy controls. The difference between the central and peripheral SAP (delta SAP) and central/ peripheral pressure correspondence index (CI) were estimated. RESULTS: Indirect arteriography has found that patients with moderate and severe COPD have stable elevated central SAP which is close to brachial SAP while in healthy controls the difference between central and peripheral SAP is 10.2 +/- 2.1 mmHg. With progression of COPD severity, deltaSAP diminishes while CI rises showing growing disproportion between central and peripheral blood pressure. In severe COPD physiological difference between them disappears. In COPD increased CAP is associated with impaired mechanical properties of the arterial bed and myocardial contractility proved by significant links between CAP and left ventricular ejection fraction index and key parameters of arterial stiffness. CONCLUSION: Aortic CAP, delta SAP and CI are additional informative criteria of COPD severity and high cardiovascular risk as shown by their close correlation with hypoxemia, severity and duration of the disease.

[Clinico-functional evaluation of arterial rigidity in bronchial asthma].

Vascular disturbances play an important role in the pathogenesis of bronchial asthma (BA). Presently, study of vascular mechanical properties, arterial rigidity in particular, is of great interest in terms of evaluation of functional condition of the cardiovascular system. It is not clear yet, whether arterial rigidity increases in patients with bronchial asthma, and what role it can play in its pathogenesis. Fifty-four patients were examined with non-invasive arteriography (arteriographer TensioClinic TL 1, TensioMed, Hungary). Aortal rigidity was in general significantly higher in patients with BA exacerbation vs. healthy controls. This was expressed by a higher pulse wave velocity in the aorta (PWVA) and augmentation index (AI) in severe and moderate BA. PWVA in BA was almost twice higher in BA patients compared with healthy people. The ratio of coronary perfusion indices (systolic and diastolic area index; SAI and DAI) was biased towards SAI. Regardless of the degree of an increase in arterial vascular rigidity in BA exacerbation, PWVA, AI, and SAI/DAI significantly improved and approximated normal values during remission, which demonstrate a transient character of these changes. In patients with severe BA AI and SAI/DAI ration were lower than in patients with moderate BA and healthy individuals, which is connected with adaptation phenomena. Correlation analysis showed that an increase in arterial rigidity is connected mostly with the degree of ventilation disorder and hypoxia as well as with the duration and severity of the disease. Further research in this direction will make it possible to know more about the exact pathophysiological mechanisms of vascular dysfunction in BA.

Peculiarities of vasomotor reaction of cerebral vessels in arterial hypertension.

We studied vasomotor activity of rat cerebral vessels. Peculiarities of endothelium-dependent reactions of cerebral arteries in induced arterial hypertension were revealed. Quantitative and qualitative relationships between the parameters of the vasomotor apparatus of cerebral arteries and parameters of circulatory homeostasis were determined.

[Relations between VDR3 and COL1A1 genes and markers of bone tissue metabolism in patients with chronic obstructive pulmonary disease].

AIM: To study correlation between polymorphism of the genes of vitamin D3 (VDR3), collagen of type 1 alpha-1 (COL1A1) and markers of bone tissue metabolism in chronic obstructive pulmonary disease MATERIAL AND METHODS: A total of 56 COPD patients were examined. Bone metabolism was evaluated by osteocalcin (OC) level and betaCL in the blood; BsmI polymorphism of gene VDR3 (genotypes BB, Bb, bb) and Sp1 polymorphism of gene COL1A1 (genotypes SS, Ss, ss)--by polymerase chain reaction. The control group consisted of 50 healthy persons of matched gender and age. RESULTS: OC and S allele were not the same in genotypes BB, Bb and bb. Ss and ss genotypes carriers had higher beta CL level than SS-carriers. SS and ss genotypes carriers did not differ with betaCL concentrations (p > 0.05). CONCLUSION: Testing of VDR3 and COL1A1 genes gives grounds for detection of predisposition to development of pulmonogenic osteopenic syndrome.