Function Of Cardiovascular System Research Articles

Exposure to synthesized tribromobisphenol A and critical effects: Metabolic pathways, disease signature, and benchmark dose derivation

2,2′,6-Tribromobisphenol A (Tri-BBPA), the main debrominated congener of tetrabromobisphenol A (TBBPA), is ubiquitous in the environment and human body but with unknown toxicity. Tri-BBPA was synthesized and applied to investigate its sub-chronic exposure effects on 28 organ coefficients and clinical health indicators related to liver function, kidney function, and cardiovascular system function in female mice. Results showed that the liver was the targeted organ of Tri-BBPA exposure. Compared to the control group, the changes in liver coefficient, cholinesterase, total protein, albumin, γ-glutamyl transpeptidase, lactate dehydrogenase, and creatine kinase levels ranged from −61.2 % to 35.5 % in the high-exposed group. Creatine kinase was identified as a critical effect indicator of Tri-BBPA exposure. Using the Bayesian benchmark dose derivation method, a lower reference dose than TBBPA was established for Tri-BBPA (10.6 μg/kg-day). Serum metabolomics revealed that Tri-BBPA exposure may primarily damage the liver by disrupting tryptophan metabolism related to L-alanine, tryptamine, 5-hydroxyindoleacetic acid, and 5-methoxyindoleacetate in liver cells and leading to liver dysfunction. Notably, epilepsy, schizophrenia, early preeclampsia, and late-onset preeclampsia were the top six enriched diseases, suggesting that the nervous system may be particularly affected by Tri-BBPA exposure. Our findings hinted a non-negligible health risk of exposure to debrominated products of TBBPA.

Characterization of heart rate variability in end-stage renal disease patients after kidney transplantation with recurrence quantification analysis.

Heart rate variability (HRV) is a noninvasive approach to studying the autonomic modulation of heart rate in experimental settings, such as active standing sympathetic stimulation. It is known that patients with end-stage renal disease during active standing have few changes in HRV dynamics, which are improved after hemodialysis. However, it is unknown whether the response to active standing is recovered after definitive treatment with kidney transplantation. This work aims to assess the change in HRV dynamics in the supine position and active standing through time and frequency-based metrics, as well as recurrence plot quantitative analysis (RQA). We studied HRV dynamics by obtaining 5-minute electrocardiographic recordings from kidney transplant recipients who underwent an active standing test. The mean duration of heartbeats and their standard deviation diminished in active standing, compared with the supine position. Also, the low-frequency component of HRV and the presence of diagonal and vertical structures in RQA were predominant. A larger estimated glomerular filtration rate was significantly correlated with broader HRV in the supine position and during active standing. The narrower HRV during active standing may indicate a sympathetic response to external stimuli, which is expected in a functional cardiovascular system, and may be influenced by renal function.

L-arginine, inosine and meldonium effect on the vascular wall reactivity of adult rats

Changes in the structure, metabolism and cardiovascular system function that develop during ageing are the basis for the circulatory pathology occurrence in old age. Currently, cardiovascular system diseases are one of the main causes of mortality in almost all developed countries. Therefore, searching for new drugs to correct the metabolism and functions of organs and systems whose activity is disrupted during ageing is an urgent problem. The article presents the study influence results of the synthesis precursor of endothelial relaxing factor - NO (ERF-NO) L-arginine, the purine nucleoside inosine and the β-oxidation inhibitor of fatty acids meldonium on the vascular wall reactivity of adult rats. When used separately, these drugs have been shown to cause slight relaxation of the thoracic aorta isolated segments in adult animals. When L-arginine, inosine and meldonium are used together, there is no summation of their pharmacological effect on blood vessels, however, some vasodilator effect potentiation is observed. The acetylcholine (Ach) vasodilator effect was significantly more than the vasodilator effect of the studied composition (L-arginine + inosine + meldonium), conventionally called Melarginine. It should be noted that, although the vasodilator Ach effect was significant, it was short-term, and the vasodilator effect of the studied combination (Melarginine) was long-lasting. A pronounced vasodilator response to Ach indicates the preservation of the endothelium in adult rats. Therefore, with intact endothelium in adult animals, Melarginine does not cause significant vascular relaxation. In aged rats, which typically exhibit endothelial damage, the effect of Melarginine may be more significant compared to adults. This will be the subject of our further study. Still, Melarginine has a small but long-lasting vasodilatory effect in adult rats, which also helps regulate vascular tone. _________________________________________________________________________________________ Keywords: vessel reactivity; endothelial dysfunction; L-arginine; inosine; meldonium; Melarginine

DOT1L is critical for adult vessel maintenance and functions.

DOT1L is the only known histone H3K79 methyltransferase essential for the development of the embryonic cardiovascular system, including the heart, blood vessels, and lymphatic vessels, through transcriptional regulation. Our previous study demonstrated that Dot1l deletion results in aberrant lymphatic development and function. However, its precise function in the postnatal cardiovascular system remains unknown. Using conditional and inducible Dot1l knockout (KO) mice, along with a reporter strain carrying the Geo gene at the Dot1l locus, DOT1L expression and its function in the vascular system during postnatal life were investigated. To assess vessel morphology and vascular permeability, we administered Latex or Evans blue dye to KO mice. In addition, in vitro tube formation and cell migration assays were performed using DOT1L-depleted human umbilical vein endothelial cells (HUVECs). Changes in the expression of vascular genes in HUVECs were measured by quantitative polymerase chain reaction. Our findings demonstrate that conditional Dot1l knockout in the Tg (Tie2-cre) strain results in abnormal blood vessel formation and lymphatic anomalies in the intestine. In a mouse model of Rosa26-creER-mediated inducible Dot1l knockout, we observed vascular phenotypes, including increased vascular permeability and brain hemorrhage, when DOT1L was deleted in adulthood. Additionally, DOT1L depletion in cultured HUVECs led to impaired cell migration and tube formation, likely due to altered gene transcription. These findings highlight the essential role of DOT1L in maintaining vascular integrity and function during embryonic development and postnatal life. Our study revealed that DOT1L is required for the maintenance of adult vascular function through the regulation of gene expression.

Post-COVID-19 Cognitive Dysfunction: Methodological Foundations for Prevention and Correction Model

The article introduces a comprehensive review of theoretical and experimental studies in the field of psychophysiological predictors of cognitive impairments in post-COVID-19 patients. The data obtained made it possible to design a model of psychological correction and prevention of post-COVID-19 cognitive dysfunction. This condition affects cognitive, behavioral, and psycho-emotional areas of mental activity. Functional changes involve poor mobility of nervous processes and short attention span, as well as changes in coping behavior and personality characteristics. Unlike older patients, teenagers experience fewer consequences for cardiovascular system and cognitive functions. As for gender differences, men restored their cognitive functions better when they came to grasp with their past experience. For women, recovery was associated with life meaning, planning, and goal setting. The resulting model for the prevention and psychological correction of post-COVID-19 cognitive dysfunction integrated the principles of systemic, information, cognitive, and personality-oriented approaches. It consisted of several structural elements that made it possible to support COVID-19 patients through all treatment stages, i.e., psychodiagnostics, psychocorrection, psychotherapy, and social and lifestyle adaptation.

Liquid respiratory desaturation. The first experience of application on large biological objects

Introduction. This article is a continuation of the publication of the experimental studies results of prevention of acute decompression sickness (aDCS) in laboratory animals by the method of liquid respiratory desaturation (LRDS). LRDS is a method of preventing decompression disorders by the excretion of metabolically indifferent gases (in particular nitrogen) from the body during spontaneous respiration with liquid or artificial liquid lung ventilation (ALLV), by dissolved gas concentration gradient "from tissues to respiratory fluid". The method allows to provide rapid desaturation of the body from metabolically indifferent gases in the process of liquid respiration before and/or during decompression, thereby creating conditions for application of ultra-fast decompression profiles without the risk of decompression disorders.
 The aim of the study was to confirm the possibility of LRDS being a method of DCS prevention on large laboratory animals (minipigs).
 Materials and methods. The studies were performed on Wiessenau minipigs (n=8) — male and female, aged 4–5.5 months and weighing 7.1–11.2 kg. Animals of the control (n=4) and experimental (n=4) groups were subjected by compression by keeping in an air environment under high pressure (absolute 0.5 MPa for 60 minutes) to saturate tissues with indifferent gas (nitrogen). After compression experimental group was exposed to 30-minute ALLV with a liquid (perfluorodecalin) saturated with an oxygen under normobaric conditions. Air environment pressure during procedure of artificial lung ventilation was kept at 0.5 MPa. Decompression of the control and experimental groups was carried out in non-stop manner for 80 and 40 seconds respectively. The investigation of severity of clinical manifestations of DCS (changes in hemodynamic and respiratory parameters) including ultrasonic examination of gas bubbles in the heart and large vessels of the liver and as well as survival of animals in groups and pathoanatomical changes was performed.
 Results of the study. Clinical manifestations, ultrasonic scanning of the heart and venous vessels of the liver, as well as morphological examination data indicated the development of severe acute post-decompression disorders (PDD) in animals of the control group, which caused deaths in 100% of cases. Meanwhile all animals in experimental group survived and their state was stable. According to ultrasonic examination, the presence of small number of gas bubbles in the right-side heart chambers and liver's venous vessels being noted, but they disappeared after several hours. Deviations of the respiration's parameters function from background values (shortness of breath of a mixed type with the participation of auxiliary muscles, etc.) observed from the 2nd to the 4th day after ALLV, as well as compensatory reactions from the cardiovascular system (heart rate variability and instability of hemodynamic parameters) were caused by ALLV.
 Conclusions. Compressed air exposure 0.5 MPa for 60 minutes followed by 80 seconds of non-stop decompression allows to provoke the severe acute PDD minipigs model, manifested by pronounced intravascular gas formation, the development of acute respiratory and cardiovascular insufficiency causing the development of adverse outcomes.
 The ultrasound method of visual assessment of intravascular gas formation severity, adapted for minipigs, together with the dynamics of changes in the indicators of respiratory and cardiovascular systems makes possible to assess not only state of animal under anesthesia, but also the effectiveness of PDD prevention measures.
 The usage of ALLV with PFC liquid completely saturated with 100% oxygen under normobaric conditions makes possible partial removal of indifferent gas (nitrogen) dissolved in tissues of experimental animals during exposition in a compressed air environment before decompression and thereby carry out the prevention of DCS by LRDS method. It makes possible to implement successfully ultra-fast decompression profiles, incompatible with life in the control group.
 The state of animals from experimental group after LRDS is characterized by lung impairment caused by ALLV in hyperbaric conditions accompanied by temporary changes of external respiration function and compensatory reactions of cardiovascular system, observed during first 4 days.
 Ethics. The study was conducted in accordance with the ethical principles of the Declaration of Helsinki. The Clinical Study Protocol was approved by local Ethics Committee of The Federal State Budgetary Scientific Institution «Izmerov Research Institute of Occupational Health».

MECHANISMS OF VASOPROTECTION AND CARDIOPROTECTION IN HYPOXYTHERAPY OF ARTERIAL HYPERTENSION AND CORONARY ARTERY DISEASE

Highlights The article presents a modern understanding of the main links of the functional circulatory regulation system and its response to exogenous hypoxia, as well as describes the data available on molecular mechanisms of vasoprotection and cardioprotection involved in response to hypoxytherapy in patients with arterial hypertension and coronary artery disease. AbstractHypoxic conditioning has taken an important place in the range of non-drug methods for stimulating the adaptive potential of a healthy person and patients with cardiovascular diseases. There are many approaches to the use of various methods of exogenous hypoxia, however, there is no consensus on the essence of sanogenetic mechanisms that provide a multi-level functional system for maintaining oxygen supply and blood circulation. Adaptive reactions of afferent, central and efferent links of the functional circulatory regulation system in hypoxia in a healthy person are described. The results of studies of physiological systemic reactions realized by respiratory and vegetative plasticity using interval (intermittent) hypoxia are presented. In patients with arterial hypertension and coronary artery disease, the facts of chemoreflective stimulation and modulation of lung ventilation, autonomic nervous system status, especially sympathetic activity of peripheral blood vessels and vagal activation of cardiac activity have been established. The main vaso- and cardioprotective properties of interval hypoxytherapy are based on the leveling of oxidative stress, inflammation, activation of angiogenesis, and a shift in the secretory activity of the endothelium towards vasodilating, antiproliferative, and antithrombotic mediators. We present the evidence for the role of shear stress and the state of glycocalyx, angiopoietin and adrenomedulline in the regulation of vascular tone, as well as cytoprotective properties of cytoplasmic and mitochondrial metabolic factors in the formation of ischemic tolerance of cardiomyocytes. The issues of the relationship between systemic (neuronal and humoral) reactions and structural and functional responses of target cells in providing adaptive/compensatory mechanisms for regulating blood circulation under the influence of exogenous hypoxia require further research and evaluation.

Signal mining and risk analysis of Alprazolam adverse events based on the FAERS database

This study aims to evaluate the safety of Alprazolam by analyzing the FAERS database, provide data analysis for monitoring adverse drug reactions. This research encompasses adverse event (AE) reports related to Alprazolam from the first quarter of 2004 to the second quarter of 2023. Four signal mining and analysis methods were utilized, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM). Further exploration was conducted regarding patient characteristics and types of AEs. A total of 23,575 AE reports in which Alprazolam was the primary suspect drug were collected, identifying 347 Preferred Term (PT) signals and 27 System Organ Classes (SOCs). The number of AE reports increased annually, especially in 2015, 2018, 2019, and 2020. The main affected groups were females and the age range of 18 to 45. Psychiatric disorders, Nervous system disorders, and Gastrointestinal disorders were the most common the organ system in which the AEs occurred. There is a certain risk of drug abuse and suicide with Alprazolam. Most notably, several AEs not recorded in the Alprazolam leaflet appeared among the top 30 PTs in signal strength, including but not limited to Benzodiazepine drug level abnormal, Acquired amegakaryocytic thrombocytopenia, Cutaneous T-cell dyscrasia, and Coronary No-reflow Phenomenon. For the first time, AEs related to the cardiovascular system and platelet function were unveiled. The severe AE reports that resulted in "hospitalization" and "death" accounted for 30.96% and 21.86%. This study highlights the risks of suicide and misuse of Alprazolam. Other potential severe or fatal AEs, such as those related to the cardiovascular system, platelet function, and others, require further research to determine their precise mechanisms and risk factors.

Comparing the Efficacy of Various Anaesthesia Protocols for Caesarean Section in Dogs

Introduction. Caesarean section is attributed with frequent deaths among newborn puppies – up to 30%, depending on the chosen anaesthetic care and the presence of aggravating factors. The right choice of drugs and anaesthetic techniques can significantly affect the clinical outcomes. Because a standardised anaesthesia protocol for the caesarean section in dogs is missing in Russia, the research in this area is very relevant. The aim of the work is to compare three variants of the anaesthesia protocols across the basic clinical outcomes of a caesarean section delivery in a dog (including intra- and postoperative results, mortality rate) and to determine the most efficient and safe one for a bitch and puppies.Materials and Methods. The research was conducted at the premises of Rostov-on-Don veterinary clinic in the period from December 2021 to December 2023. There were selected 63 pregnant bitches who met the inclusion and exclusion criteria at that period of time. The animals were divided into three groups: in the first group the anaesthetic care included induction with propofol, intraoperative inhalation anaesthesia with sevoflurane and epidural lidocaine anaesthesia; in the second group the induction and maintenance of anaesthesia was performed with propofol, alongside the local anaesthesia with lidocaine was administered; the third group was administered propofol and inhalation anaesthesia with sevoflurane, excluding epidural anaesthesia. Monitoring was carried out according to the intraoperative indicators, post-anaesthesia recovery time, postoperative indicators of fear and pain, Apgar scores in puppies, the number of survivors and deaths in the short-term (30 minutes) and medium-term (during the day) periods.Results. The best intra- and postoperative indicators as well as the highest percentage of surviving puppies and the smallest number of stillbirths were revealed in patients of the first group. Medium results were recorded in the third group. The lowest intraoperative indicators in the function of cardiovascular and respiratory systems and the worst results as of hypoxia in newborn puppies were recorded in the second group of studied animals.Discussion and Conclusion. When determining the most efficient anaesthetic care for caesarean section in dogs, it should be borne in mind that propofol has a depressing effect on the respiratory and cardiovascular systems of patients, therefore its use is highly undesirable for the anaesthesia maintenance. Unlike propofol, sevoflurane does not penetrate the placenta barrier, is not metabolised and enables quick awakening of a bitch from anaesthesia. Moreover, in cases, when sevoflurane was used, the Apgar scores in the born puppies were the highest. Epidural anaesthesia with lidocaine reduces the postoperative pain of a bitch after caesarean section and has a positive effect on lactation. The use of epidural anaesthesia may be complicated with hypotension, however, the preventive use of crystalloid solutions, can mitigate this effect. Thus, the protocol with triple anaesthesia is optimal and preferable for caesarean section in dogs: induction with propofol, epidural anaesthesia with lidocaine and inhalation with sevoflurane to maintain anaesthesia.

The β-catenin C terminus links Wnt and sphingosine-1-phosphate signaling pathways to promote vascular remodeling and atherosclerosis.

Canonical Wnt and sphingosine-1-phosphate (S1P) signaling pathways are highly conserved systems that contribute to normal vertebrate development, with key consequences for immune, nervous, and cardiovascular system function; despite these functional overlaps, little is known about Wnt/β-catenin-S1P cross-talk. In the vascular system, both Wnt/β-catenin and S1P signals affect vessel maturation, stability, and barrier function, but information regarding their potential coordination is scant. We report an instance of functional interaction between the two pathways, including evidence that S1P receptor 1 (S1PR1) is a transcriptional target of β-catenin. By studying vascular smooth muscle cells and arterial injury response, we find a specific requirement for the β-catenin carboxyl terminus, which acts to induce S1PR1, and show that this interaction is essential for vascular remodeling. We also report that pharmacological inhibition of the β-catenin carboxyl terminus reduces S1PR1 expression, neointima formation, and atherosclerosis. These findings provide mechanistic understanding of how Wnt/β-catenin and S1P systems collaborate during vascular remodeling and inform strategies for therapeutic manipulation.

Effects of war-related stress on the cardiovascular system, metabolism and the rate of ageing in women

Chronic war-related stress (WRS) due to disruption of adaptation mechanisms can affect physiological processes in the body, in particular, metabolism, neuroendocrine regulation, and the state of the cardiovascular and respiratory systems. WRS can also cause changes in the body's rate of ageing. Purpose of the Study: To investigate the effects of WRS on the cardiovascular system, metabolism and the rate of ageing in women. The study included 91 women aged from 30 to 74 years who experienced chronic WRS and 79 women examined before the Russian-Ukrainian war (control group). The biological age (BA) was determined according to the indicators of hemodynamics, heart rate variability and metabolism (cardiometabolic age) using a formula that was obtained by multiple stepwise regression. The indicators were selected, which correlate as much as possible with age and little among themselves. During the war, no statistically significant changes in heart rate, or systolic and diastolic blood pressure were observed, but a significant reduction in overall HRV in the supine position was obtained. Additionally, indices of parasympathetic nervous system activity are significantly lower during the war. In women, examined during the war, there is a statistically significant higher concentration of blood plasma glucose at fasting and 2-hour post-standard oral glucose tolerance test, they also exhibit higher plasma insulin concentration and a higher HOMA-IR index. An increased frequency of prediabetic disorders was observed. So, in the group of women examined before the war, an elevated fasting blood plasma glucose level was found in 6 %, while during the war it was observed in 19 %. Impaired glucose tolerance before the war was present in 10 % of women, and during the war, it increased to 25 %. To assess the effect of WRS on the rate of ageing, the BA of women before and during war was calculated. The formula for calculating BA was obtained on a group of healthy women before the war, and the ageing rate was calculated as the difference between BA and chronological age (CA). The average BA in the group of women before the war was 56.5±1.4 years, and in the group during the war – 64.7 ± 1.1 years. The difference between BA and CA is (0.02 ± 0.79) years in the women before the war and (10.8 ± 1.36) years during the war (p < 0.05). Chronic WRS leads to the disruption of the cardiovascular system's functioning and simultaneously triggers an imbalance in the autonomic nervous control in women. These changes indicate a state of heightened stress. Women exposed to chronic WRS experience unfavourable alterations in carbohydrate and lipid metabolism, increasing the risk of diabetes mellitus development. Chronic WRS accelerates the rate of cardiometabolic ageing in women. _________________________________________________________________________________________ Keywords: cardiovascular system; metabolism; biological age; war-related stress; woman

Impact of interstitial lung disease on left ventricular myocardial function.

Interstitial lung disease (ILD) comprises a wide variety of pulmonary parenchymal disorders within which progressive fibrosing ILD (PF-ILD) constitutes a phenotypic subset. By use of speckle tracking-based strain analysis we aimed to evaluate the degree of left ventricular (LV) dysfunction in progressive vs. non-progressive fibrosing ILD (non-PF-ILD). A total of 99 ILD patients (mean age 63.7 ± 13.5 years, 37.4% female), composed of 50 PF-ILD and 49 non-PF-ILD patients, and 33 controls were prospectively enrolled and underwent conventional and speckle tracking echocardiography. Additional laboratory and pulmonary function testing, as well as six-minute walk test were performed. As compared to the non-PF-ILD cohort, PF-ILD patients exhibited a significantly impaired forced vital capacity (2.4 ± 1.0l vs. 3.1 ± 0.9l, p = 0.002), diffusion capacity for carbon monoxide (DLCO, 25.6 ± 16.3% predicted vs. 43.6 ± 16.67% predicted, p <0.001) and exercise capacity response as measured by the six-minute walk test distance (268.1 ± 178.2m vs. 432.6 ± 94.2m, p <0.001). Contrary to conventional echocardiographic LV parameters, both regional and global longitudinal LV strain measurements were significantly altered in ILD patients as compared to controls. No differences in LV strain were found between both patient groups. Significant correlations were observed between global longitudinal strain, on the one hand, and systemic inflammation markers, total lung capacity (TLC) and DLCO, on the other hand (high-sensitivity C-reactive protein: Pearson´s r = -0.30, p< 0.001; interleukin-6: Pearson´s r = -0.26, p = 0.007; TLC % predicted: Pearson´s r = 0.22, p = 0.02; DLCO % predicted: Pearson´s r = 0.21, p = 0.02). ILD is accompanied by LV dysfunction. LV functionality inversely correlates with the severity of the restrictive ventilatory defect and inflammation marker levels. These observations support the assumption of persistent low-grade systemic inflammation that may link systemic cardiovascular function to ILD status.

Phosphorylated α-synuclein deposited in Schwann cells interacting with TLR2 mediates cell damage and induces Parkinson’s disease autonomic dysfunction

Despite the significant frequency of autonomic dysfunction (AutD) in Parkinson’s disease (PD) patients, its pathogenesis and diagnosis are challenging. Here, we aimed to further explore the mechanism of phosphorylated α-synuclein (p-α-syn) deposited in vagus nerve Schwann cells (SCs) causing SCs damage and PD AutD. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 20 mg/kg) was administrated to C57BL/6 mice twice a week for 35 days. Following the final injection, locomotor functions, gastrointestinal symptoms, urine functions, and cardiovascular system functions were evaluated. Meanwhile, we examined p-α-syn deposited in vagus nerve SCs, Toll-like receptor 2 (TLR2) activation, and SCs loss using immunofluorescence, western blot, and Luxol fast blue staining. In vitro, the rat SCs line RSC96 cells were exposed to α-synuclein preformed fibril (α-syn PFF), and cell viability was detected by CCK8. Co-IP was used to identify the interaction between p-α-syn and TLR2. Furthermore, the role of TLR2 in p-α-syn-mediated SCs damage was confirmed by the administration of CU-CPT22, a specific blocker of TLR2. In vivo, apart from dyskinesia, MPTP mice exhibited constipation, urinary dysfunction, and cardiovascular failure, which were associated with the deposition of p-α-syn in vagus nerve SCs, TLR2 activation, and vagus nerve demyelination. In vitro, stimulation of α-syn PFF induced a time-dependent loss of viability, and p-α-syn deposited in RSC96 cells induced a cellular inflammatory response by interacting with TLR2, resulting in cell dysfunction and apoptosis. However, both SCs inflammatory response and cell viability were alleviated after inhibition of TLR2. Furthermore, 1 h fecal pellets and water content, the frequency of 1 h urine, blood pressure, heart rate, and heart rate variability of mice in the MPTP + CU-CPT22 group were also improved. Our results support the perspective that p-α-syn interacts with TLR2 induced SCs damage and is involved in PD AutD, which sheds fresh light on the mechanism of PD AutD and indicates a promising treatment for PD AutD targeting SCs p-α-syn/ TLR2 signaling pathway.

Vascular development, remodeling and maturation.

The development of the vascular system is crucial in supporting the growth and health of all other organs in the body, and vascular system dysfunction is the major cause of human morbidity and mortality. This chapter discusses three successive processes that govern vascular system development, starting with the differentiation of the primitive vascular system in early embryonic development, followed by its remodeling into a functional circulatory system composed of arteries and veins, and its final maturation and acquisition of an organ specific semi-permeable barrier that controls nutrient uptake into tissues and hence controls organ physiology. Along these steps, endothelial cells forming the inner lining of all blood vessels acquire extensive heterogeneity in terms of gene expression patterns and function, that we are only beginning to understand. These advances contribute to overall knowledge of vascular biology and are predicted to unlock the unprecedented therapeutic potential of the endothelium as an avenue for treatment of diseases associated with dysfunctional vasculature.

Melatonin reduces myocardial cell damage in myocardial ischemia/reperfusion rats by inhibiting NLRP3 activation.

Melatonin (Mel) is an endogenous hormone with many pharmacological effects, such as sedation, hypnosis, antidepressant, blood pressure regulation, anti-inflammatory and anti-tumor. It is mainly synthesized by pineal gland in vivo. Mel can regulate the function of cardiovascular system and effectively reduce myocardial cell injury, thus playing a role in myocardial protection, but its specific mechanism is unclear. Ischemia-reperfusion injury (IRI) often leads to poor prognosis and complications in patients with cardiovascular diseases, and inflammatory reaction mediated by nod-like receptor thermoprotein domain-related protein 3(NLRP3) is an important reason for the further aggravation of subsequent injury after IRI. Rats were intervened with Mel or NLRP3 inhibitor MCC950 for 10 days, and then the IRI rat model was established. After that, rats were anesthetized and killed, and myocardial tissues were collected for experiments. The experimental results showed that Mel reduced the myocardial infarction area, decreased aspartate aminotransferase (AST), creatine kinase myocardial band (CK-MB), lactate dehydrogenase (LDH) and malondialdehyde (MDA), and significantly inhibited the expression of reactive oxygen species (ROS), NLRP3, caspase-1 and apoptosis-associated speck-like protein containing a CARD (ASC), but its effect on superoxide dismutase (SOD) was opposite. Therefore, Melmay improve autophagy and inflammation during myocardial ischemia/reperfusion and may decrease myocardial cell damage by inhibitingNLRP3.

CARDIOVASCULAR INDICATORS OF ATHLETES IN SOMATOTYPE-RELATED RESPONSE TO PHYSICAL ACTIVITY

In order to achieve high sports results, a comprehensive study of the athlete’s body is necessary. The morphofunctional study is the most informative and accessible. However, the somatotype-related functional state of the cardiovascular system of athletes remains insufficiently studied. The purpose of the research: To determine the indicators of the cardiovascular system of athletes in response to physical exertion, depending on the somatotype according to Reese-Eysenck. An anthropometric and functional study of the cardiovascular system of 49 athletes of the highest sports skill engaged in freestyle wrestling at the Sakha Republic’s Center for Traditional Sports was conducted. The Reese-Eysenck index was used to determine the somatotype. Functional examination of the cardiovascular system included blood pressure measurement and pulse counting at rest, then 1 and 2 minutes after exercise. The exercise consisted of a full squat with arms outstretched with a frequency of 20 squats in 30 seconds. In order to determine the tolerance of physical activity, the Roufier index was calculated. The adaptive potential of the cardiovascular system is determined using the index of functional changes. Somatotyping by the Reese-Eysenck index among the examined athletes revealed that a significantly large proportion of the examined individuals had an athletic somatotype. In pyknics, significantly large indicators of body weight and the transverse diameter of the chest were recorded. A functional examination of the cardiovascular system with the use of physical activity revealed a significantly greater increase in systolic blood pressure after 1 and 2 minutes and heart rate 1 minute after physical activity in individuals with the pyknic somatotype compared with others. The analysis of the results of the index of functional changes of athletes depending on the somatotype revealed the stress of the cardiovascular system function only in athletes of the pyknic somatotype. The obtained results indicate that the training process should be selected individually, taking into account the somatotype of an athlete, since among pyknics there are people with stress of the cardiovascular system with good results of physical activity tolerance according to the Roufier index.

Changes in brain function and heart sound in acute sleep deprivation individuals

AimsSleep deprivation (SD) has become a health problem in modern society due to its adverse effects on different aspects. However, the relationship between sleep and cardiovascular system function remains unclear. Here we explored the changes occurring in the brain and the heart sounds after SD. MethodsNinety healthy adult men were recruited and subjected to 36 h of Sleep Deprivation (SD). They participated in a number of tests, including measurements of the heart sound, blood oxygen, and heart rate every 2 h. By using of principal component analysis to reduced the dimensionality of heart sound data. While the ALFF and ReHo indexes were measured via fMRI before and after SD. Correlation and regression analyses were used to reveal the relationship between fMRI and heart sound changes due to SD. ResultsIn this study, there were no abnormal values in the heart rate and blood oxygen during 36 h of SD, whereas the intensity of heart sounds fluctuated significantly increased and decreased. The ALFF was increased in bilateral pericalcarine(Calcarine), left anterior cuneus, (Precuneus_L), right superior temporal gyrus(Temporal_Sup_R), left supplementary motor area (Supp_Motor_Area_L); However, it was reduced in the right medial superior frontal gyrus (Frontal_Sup_Medial_R), right dorsolateral superior frontal gyrus (Frontal_Sup_R) and left medial frontal gyrus (Frontal_Mid_L). The regression analysis uncovered that the intensity of the heart sound in the systole, s1, and s2 phase could be explained by Calcarine_L changes. ConclusionAcute sleep deprivation affects cardiac-brain axis and the specific brain regions. Calcarine_L changes during sleep deprivation are involved in regulating heart contractions.

A cell-and-plasma numerical model reveals hemodynamic stress and flow adaptation in zebrafish microvessels after morphological alteration.

The development of a functional cardiovascular system ensures a sustainable oxygen, nutrient and hormone delivery system for successful embryonic development and homeostasis in adulthood. While early vessels are formed by biochemical signaling and genetic programming, the onset of blood flow provides mechanical cues that participate in vascular remodeling of the embryonic vascular system. The zebrafish is a prolific animal model for studying the quantitative relationship between blood flow and vascular morphogenesis due to a combination of favorable factors including blood flow visualization in optically transparent larvae. In this study, we have developed a cell-and-plasma blood transport model using computational fluid dynamics (CFD) to understand how red blood cell (RBC) partitioning affect lumen wall shear stress (WSS) and blood pressure in zebrafish trunk blood vascular networks with altered rheology and morphology. By performing live imaging of embryos with reduced hematocrit, we discovered that cardiac output and caudal artery flow rates were maintained. These adaptation trends were recapitulated in our CFD models, which showed reduction in network WSS via viscosity reduction in the caudal artery/vein and via pressure gradient weakening in the intersegmental vessels (ISVs). Embryos with experimentally reduced lumen diameter showed reduced cardiac output and caudal artery flow rate. Factoring in this trend into our CFD models, simulations highlighted that lumen diameter reduction increased vessel WSS but this increase was mitigated by flow reduction due to the adaptive network pressure gradient weakening. Additionally, hypothetical network CFD models with different vessel lumen diameter distribution characteristics indicated the significance of axial variation in lumen diameter and cross-sectional shape for establishing physiological WSS gradients along ISVs. In summary, our work demonstrates how both experiment-driven and hypothetical CFD modeling can be employed for the study of blood flow physiology during vascular remodeling.

Role of copper and its complexes in cardiovascular diseases.

Copper is a trace element essential for the maintenance of normal physiological functions in cardiovascular system, and its transport and metabolisms are regulated by various copper proteins such as copper-based enzymes, copper chaperones and copper transporters. The disturbance of copper level or abnormal expression of copper proteins are closely associated with the development of cardiovascular diseases such as atherosclerosis, hypertension, ischemic heart disease, myocardial hypertrophy and heart failure. Thus, intervention of copper ion signaling pathways is expected to be an effective measure for treating cardiovascular diseases. Some copper complexes, such as trientine, copper-aspirinate complex and copper (II) diethyldithiocarbamate, have been found to play a role in the prevention and treatment of cardiovascular diseases and possess potential prospects. Exploring the role of copper in maintaining normal cardiovascular status and the potential application of copper complexes in the treatment of cardiovascular diseases may lay a foundation for finding new targets for prevention and treatment of various cardiovascular diseases, and provide new ideas for clinical treatment of cardiovascular diseases.

Зависимость основных показателей деятельности сердечно-сосудистой системы от индекса массы тела у подростков магаданской области

Excess weight and obesity detected in adolescence are likely to be detected in adulthood, which increases the risk of cardiovascular disorders. The study was aimed to assess the features of cardiovascular system parameters in adolescent males considering their body mass index (BMI). For this purpose a total of 208 adolescent males aged 15–16 were surveyed. The major indicators of physical development and cardiovascular system function were evaluated by standard method. BMI was calculated, based on which three groups were distinguished: underweight adolescents, adolescents with normal and excess body weight. It was found that 23% of subjects were underweight, 62% had normal body weight, and excess body weight was reported in 15% of adolescents. It has been shown that the growth of strain on the cardiovascular system from the group of underweight adolescents to the group with excess weight is observed (4, 16, and 37%, respectively), which is confirmed by the correlation analysis results. The findings suggest the less effective cardiovascular system functioning mode in overweight adolescents compared to other assessed groups. The data obtained can be used to develop the guidelines on managing excess body weigth in the group of individuals being through the adolescent ontogeny period as a target group for health promotion and applying preventive measures.