Resistance Blood Vessels Research Articles

The significance of pulsatility indices in the middle cerebral, internal carotid, and common carotid arteries for small vessel disease in the brain: A retrospective cross-sectional study

Background and objectives. The pulsatility index (PI) indicates the resistance in distant blood vessels and the stiffness of major arteries outside the brain. For cerebral small vessel disease (CSVD), our aim is to enhance our comprehension of the Pulsatility Index (PI) in the common carotid artery (CCA), internal carotid artery (ICA), and middle cerebral artery (MCA). Materials and methods. This study is a cross-sectional retrospective research, which was conducted between January 2020 and June 2020 at the Dr. Cipto Mangunkusumo National Hospital, Indonesia. Patients were divided into groups with CSVD and without CSVD. Univariate and bivariate analyses, along with Spearman correlation and multivariate regression, were conducted to assess the mean difference. The overall score for CSVD was determined based on findings from brain MRI scans. Results. The median age of the 79 participants was 60 years (49-66). CSVD made up 54.4% of the total. The median (interquartile range) PI values for the CCA, ICA, and MCA in cases of CSVD were 1.48 (1.3-1.68), 1.12±0.3, and 1.11 (0.95-1.38), respectively. Despite this, no significant differences in PI were observed between the groups. In cases of total stroke, the PI of the CCA showed a moderate correlation with the PI of the MCA (B 0.4, p=0.001) and the PI of the ICA (B 0.34, p=0.005). However, no correlation was found between PI and either the burden of CSVD or the total score for small vessel disease. Conclusions. The pulsatility indices for the CCA, ICA, and MCA generally rise in cases of CSVD, indicating heightened resistance in distal blood vessels and increased stiffness in the large arteries outside the skull. This highlights the potential use of PI measurement as a promising adjunctive screening and evaluation tool in CSVD.

HbA1c and Pulsatility Index in Middle Cerebral Artery of Patients with Acute Thrombotic Stroke

Highlights:1. The findings of this study indicate that clinicians should remain vigilant, as effective glycemic control, reflected by optimal HbA1c levels, does not necessarily correlate with favorable distal cerebrovascular resistance, as measured by pulsatility index (PI).2. This study recommends that patients with acute thrombotic stroke undergo a comprehensive examination to ensure an accurate diagnosis and appropriate treatment. Abstract Stroke is the second leading cause of death and disability in the world. Diabetes mellitus is a risk factor for stroke with an increase in blood viscosity associated with hyperglycemia, and HbA1c is a well-established biomarker primarily used for the long-term monitoring of glycemic control in patients with diabetes mellitus. The Pulsatility index (PI) parameter of Trans Cranial Doppler (TCD) can measure blood vessel resistance. This study was to prove the correlation between HbA1c and PI in Middle Cerebral Artery (MCA) of acute thrombotic stroke patients. A cross-sectional study was conducted to thrombotic stroke patients treated at the neurological ward of Dr. Soetomo General Academic Hospital, Surabaya, Indonesia from March 2019 to April 2020 who met the inclusion and exclusion criteria. Data were obtained from medical records. Statistical analysis was performed using Spearman test for numerical data and Chi-square for categorical data with a significant value of p <0.05. There were 32 subjects who met the inclusion and exclusion criteria. A total of 24 subjects (75%) were males and 8 (25%) females with a mean age of 56.41±13.22 years. PI MCA results were abnormal in 14 subjects (43.75%) with an average of 1.8±0.97 and PI MCA was normal in 18 subjects (56.25%) with an average of 0.87±0.15. The average HbA1c was 6.55±1.9%. There was no statistically significant association observed between HbA1c and PI in MCA examination (r=0.07; p=0.73). In conclusion, the findings of this study indicate the lack of correlation between pulsatility index and HbA1c in patients with acute ischemic stroke. This underscores the importance of comprehensive cerebrovascular evaluation regardless of HbA1c status.

Optimizing the functional state of the cardiorespiratory system of female students aged 17-19 with the help of a modified program of distance classes in physical education

The article deals with the peculiarities of the impact of a modified program of distance training on physical education on the functional state of circulatory systems and external breathing of students of 17-19 years of higher education. The relevance and practical importance of this study is due to the complex modern conditions of life of our country, the inability to conduct full -fledged classes among student youth and the need to maintain the optimal level of physical and functional state of student youth. The use among female students of the experimental group of the program of remote classes proposed by us contributed to significantly higher rates of improvement in heart rate, all types of blood pressure, Robinson's index, total peripheral resistance of blood vessels, coefficient of efficiency of blood circulation, vital capacity of the lungs (in 2-3 times), breath retention time on inhalation and exhalation (3 and 5 times, respectively), Skibinsky index 5 times, hypoxia index (20 times) and almost 5 times the levels of the functional state of the cardiovascular system and the external system breath. The results of changes in their intragroup distribution by the levels of levels of functional state of circulatory and external respiration, which were reflected in the increase of their representation in functional classes high and above average, were significantly more optimal in the experimental group. Similar changes in the girls of the control group were insignificant. The results testified to the high efficiency of the proposed program of distance classes with the use of fitness and the possibility of its practical use among students of higher education.

RISK FACTORS FOR ARTERIAL STIFFNESS IN ADOLESCENCE

Objective: To investigate the arterial stiffness and risk factors in adolescence. Arterial stiffness often (AS) results from the degenerative process of the media layer of elastic arteries causing rigidity of the arteries. Arterial stiffness increases with age and it is associated with several risk factors as a disease predictor. But, arterial stiffness can be also increased in a healthy arteries as well. The increased sympathetic activity promotes vasoconstriction of resistant blood vessels i.e. arteries and arterioles that result in peripheral vasoconstriction. Adolescence age is the most important period of life for promoting future health. The certain dynamic risk factors in adolescence like, emotional dysregulation, psychological family stress, education pressure, lack of sleep, gambling, substance abuse, smartphone overuse and obesity can cause arterial stiffness. Design and method: The prospective open randomized study was designed. Adolescence age between 10 and 19 years have been investigated for increased arterial stiffness and risk factors. The inclusion criteria was healthy adolescence, while exclusion criteria was any disorder present. Arterial stiffness, non-invasive blood pressure and pulse wave datas have been measured using Agedio device. The risk factors were evaluated in every subject. The vascular age have been outlined as the final measure. Results: The preliminary results indicate the increase of Augmentation Index and Coefficient of Reflection. The average percentage of Augmentation Index was 40% and Coefficient of Reflection 65% (normal value 28% and 60% respectively). The main risk factors were educational pressure, lack of sleep and smartphone influence. The vascular age was on average, 3 years higher than biological age. Conclusions: Arterial stiffness in adolescence is increased mainly by peripheral vasoconstriction, manifested with Augmentation index and Coefficient of wave Reflection.

Death-associated protein kinase 3 regulates the myogenic reactivity of cerebral arteries.

What is the central question of this study? DAPK3 contributes to the Ca2+ -sensitization of vascular smooth muscle contraction: does this protein kinase participate in the myogenic response of cerebral arteries? What is the main finding and its importance? Small molecule inhibitors of DAPK3 effectively block the myogenic responses of cerebral arteries. HS38-dependent changes to vessel constriction occur independent of LC20 phosphorylation, and therefore DAPK3 appears to operate via the actin cytoskeleton. A role for DAPK3 in the myogenic response was not previously reported, and the results support a potential new therapeutic target in the cerebrovascular system. The vascular smooth muscle (VSM) of resistance blood vessels is a target of intrinsic autoregulatory responses to increased intraluminal pressure, the myogenic response. In the brain, the myogenic reactivity of cerebral arteries is critical to homeostatic blood flow regulation. Here we provide the first evidence to link the death-associated protein kinase 3 (DAPK3) to the myogenic response of rat and human cerebral arteries. DAPK3 is a Ser/Thr kinase involved in Ca2+ -sensitization mechanisms of smooth muscle contraction. Ex vivo administration of a specific DAPK3 inhibitor (i.e., HS38) could attenuate vessel constrictions invoked by serotonin as well as intraluminal pressure elevation. The HS38-dependent dilatation was not associated with any change in myosin light chain (LC20) phosphorylation. The results suggest that DAPK3 does not regulate Ca2+ sensitization pathways during the myogenic response of cerebral vessels but rather operates to control the actin cytoskeleton. A slow return of myogenic tone was observed during the sustained ex vivo exposure of cerebral arteries to HS38. Recovery of tone was associated with greater LC20 phosphorylation that suggests intrinsic signalling compensation in response to attenuation of DAPK3 activity. Additional experiments with VSM cells revealed HS38- and siDAPK-dependent effects on the actin cytoskeleton and focal adhesion kinase phosphorylation status. The translational importance of DAPK3 to the human cerebral vasculature was noted, with robust expression of the protein kinase and significant HS38-dependent attenuation of myogenic reactivity found for human pial vessels.

Effect of V-Shaped Groove Microstructure on Blood Flow Resistance in Bionic Artificial Blood Vessels

This study aims to investigate the blood flow in bionic artificial blood vessels and to reduce the resistance to blood flow, the drag reduction characteristics of V-shaped groove drag reduction microstructures in artificial blood vessel structures were investigated in depth. By varying the parameters of incoming flow velocity, groove width, and groove depth, the effect of various variable conditions on the drag reduction effect of the grooves was investigated, and the flow field characteristics and drag reduction effect of the V-shaped groove microstructure in the artificial blood vessel were obtained. A detailed analysis of the effect of velocity and groove size on the drag reduction effect of the groove was also carried out to demonstrate the drag reduction mechanism of the V-shaped groove microstructure and to summarize the variation law of the drag reduction rate of the V-shaped groove. The results show that the resistance reduction rate of the V-shaped groove microstructure decreases with the increase of blood flow velocity, increases with the increase of groove width, and increases and then decreases with the increase of groove depth. The velocity range used in this paper is 0.3–0.6 m/s, the groove width varies from 0 to 0.3 mm, and the groove depth varies from 0 to 0.3 mm.

The prospects of using apples and pears to obtain biologically active substances

Relevance. Apples and apple juices are healthy food products with a large amount of biologically active substances. The polyphenols contained in them are powerful natural antioxidants. They prevent the development of many chronic heart diseases and have many pharmacological properties. Thus, polyphenols increase the resistance of blood vessels, improve blood circulation, protect elastin and collagen fibers, and serve as fundamental elements supporting skin tissues. Apples contain such practically valuable substances as pectins. At the same time, in fresh apples, protopectin prevails over soluble pectin and makes up 52.3– 97.0% of the total amount.Methods. The objects of the study were the fruits of apple varieties: Voskhod, Talgar Bayterek, Sarkyt and Saya, as well as pear varieties: Bostandyk, Nagima, Sylyk, Zhazdyk. The fruits of apples and pears were harvested from September to mid-October 2021 in Saryagash district, in the farm "Tenge". Experimental data were obtained in the laboratory of the South-Kazakhstan University named after M. Auezov. At the first stage of the study, the quality of apples was determined in accordance with the requirements of GOST R 54697–2011. At the second stage, physico-chemical parameters were determined according to standard methods. The content of soluble solids was determined by the refractometric method using a refractometer, at ambient temperature 20±0.5 °C, The mass fraction of dry substances was determined by the refractive index. The sum of sugars — according to the Bertrand method.Result. Studies have established that the fruits of all studied varieties of apples and pears grown in Kazakhstan, according to organoleptic and physico-chemical indicators, contain high levels of chemicals and phenolic compounds, but the most valuable source of biologically active substances were apples of variety Baiterek and pears of variey Zhazdyk.

Effects of different preservation methods of human iliac veins.

With the progress of vascular anastomosis technology, the radical resection surgery of cancer combining with vascular resection and reconstruction has been focused by surgeon. As a natural substitute material for blood vessel, vascular allografts have good vascular compliance and histocompatibility. Generally, the donated veins could not be used immediately, and need to be well preserved. So, it is greatly significant to do research in the preservation effects of different preservation methods on veins. In this study, the effects of different preservative methods of human iliac veins were compared and analyzed in terms of cell viability, vascular wall structure and tension resistance. The donated human iliac veins were randomly divided into three groups: Cold Storage Group (4 °C) (CSG), Frozen Storage Group (-186 °C) (FSG)and Fresh Control Group (FCG). Six detection time-points of preservation for 1, 3, 5, 7, 14, 28days were set respectively. There are ten samples in each group and each time-point separately. Survival and apoptosis of vascular cell were evaluated by MTT assay and Tunel fluorescence staining. Tensile test was used to evaluate mechanical properties of vessels. The changes of vascular endothelial cells, smooth muscle cells, collagen fibers and elastic fibers were evaluated by HE staining, Masson staining and EVG staining. Furthermore, the changes of organelles were observed by transmission electron microscope. With the extension of preservation period, the vascular cell viability and tension resistance of two groups decreased, and the apoptotic cells increased gradually. The apoptosis index of CSG was higher than FSG at each time point (P < 0.05). In terms of cell viability, CSG was higher within 3days (P < 0.05), both groups were same between 3 and 14days, and then CSG lower than FSG after 14days (P < 0.05). In terms of tension resistance, CSG was stronger than FSG (P < 0.05) in first 7days, both groups were same in 2nd week, and then CSG was weaker in 4th week (P < 0.05). In terms of vascular wall structure, in CSG, vascular endothelial cells were damaged and shed, smooth muscle cells were edema after 14days, but the cell membrane and intercellular connection were still intact. In 4th week, endothelial cells were completely damaged and shed, the boundary of smooth muscle cell membrane was unclear, intercellular connection was damaged. Moreover, organelles were destroyed and disappeared, perinuclear condensation of chromatin was observed, and some cells had incomplete nuclear membrane or nuclear fragmentation; However, there were no obvious changes in the FSG within 28days. Finally, local exfoliation and destruction of endothelial cells and edema-like changes of organelles were observed; the collagen fibers and elastic fibers of blood vessels in the two groups had no obvious damage and change within 28days. For excised human iliac vein, cold and frozen storage can effectively preserve the cell viability, wall structure and tension resistance of blood vessels. With the extension of preservation time, the related performance of vessels declined in varying degrees. Within first week, the effect of cold storage is better than frozen storage, but frozen storage is significantly better than cold storage after 2weeks.

Nurses' knowledge regarding treatment and prevention of pregnancy induced hypertension

Background: Pregnancy induced hypertension (PIH) is a condition where in vasospasm occurs during pregnancy in both the small and large arteries in the body. Pregnancy Induced Hypertension is a form of high blood pressure in pregnancy. It occurs in about 5 percent to 8 percent of all pregnancies. With high blood pressure, there is an increase in the resistance of blood vessels. This may hinder blood flow in many different organ systems in the expectant mother including the liver, kidneys, brain, uterus, and placenta. The aims to assess nurses' knowledge regarding treatment and prevention of pregnancy induced hypertension and find out the association between knowledge of nurses and demographic characteristics. Methods: The study used a quantitative descriptive correlation research design. A convenience non-probability sample of 52 nurses working in primary health care centers was chosen and a self-administered questionnaire was completed. The data was gathered during a three-month period. The questionnaire's reliability is evaluated through a pilot research, and its validity is determined by a panel of (12) experts. The data is analyzed using descriptive and inferential statistical data analysis methods such as frequencies, percentages, mean of scores, and standard deviation.

Mathematical modeling of the hematocrit influence on cerebral blood flow in preterm infants.

Premature birth is one of the most important factors increasing the risk for brain damage in newborns. Development of an intraventricular hemorrhage in the immature brain is often triggered by fluctuations of cerebral blood flow (CBF). Therefore, monitoring of CBF becomes an important task in clinical care of preterm infants. Mathematical modeling of CBF can be a complementary tool in addition to diagnostic tools in clinical practice and research. The purpose of the present study is an enhancement of the previously developed mathematical model for CBF by a detailed description of apparent blood viscosity and vessel resistance, accounting for inhomogeneous hematocrit distribution in multiscale blood vessel architectures. The enhanced model is applied to our medical database retrospectively collected from the 254 preterm infants with a gestational age of 23–30 weeks. It is shown that by including clinically measured hematocrit in the mathematical model, apparent blood viscosity, vessel resistance, and hence the CBF are strongly affected. Thus, a statistically significant decrease in hematocrit values observed in the group of preterm infants with intraventricular hemorrhage resulted in a statistically significant increase in calculated CBF values.

Hypertension and Stroke Cardiovascular Control Evaluation by Analyzing Blood Pressure, Cerebral Blood Flow, Blood Vessel Resistance and Baroreflex.

Cardiovascular diseases have been the leading causes of mortality in Taiwan and the world at large for decades. The composition of cardiovascular and cerebrovascular systems is quite complicated. Therefore, it is difficult to detect or trace the related signs of cardiovascular and cerebrovascular diseases. The characteristics and changes in cardiopulmonary system disease can be used to track cardiovascular and cerebrovascular disease prevention and diagnosis. This can effectively reduce the occurrence of cardiovascular and cerebrovascular diseases. This study analyzes the variability in blood pressure, cerebral blood flow velocity and the interaction characteristics using linear and nonlinear approaches in stroke, hypertension and healthy groups to identify the differences in cardiovascular control in these groups. The results showed that the blood pressure and cerebral blood flow of stroke patients and hypertensive patients were significantly higher than those of healthy people (statistical differences (p < 0.05). The cerebrovascular resistance (CVR) shows that the CVR of hypertensive patients is higher than that of healthy people and stroke patients (p < 0.1), indicating that the cerebral vascular resistance of hypertensive patients is slightly higher. From the patient’s blood flow and vascular characteristics, it can be observed that the cardiovascular system is different from those in healthy people. Baroreflex sensitivity (BRS) decreased in stroke patients (p < 0.05). Chaotic analysis revealed that the blood pressure disturbance in hypertensive patients has a higher chaotic behavior change and the difference in initial state sensitivity. Cross-correlation (CCF) analysis shows that as the course of healthy→hypertension→stroke progresses, the maximum CCF value decreases significantly (p < 0.05). That means that blood pressure and cerebral blood flow are gradually not well controlled by the self-regulation mechanism. In conclusion, cardiovascular control performance in hypertensive and stroke patients displays greater variation. This can be observed by the bio-signal analysis. This analysis could identify a measure for detecting and preventing the risk for hypertension and stroke in clinical practice. This is a pilot study to analyze cardiovascular control variation in healthy, hypertensive and stroke groups.

Зміни центральної гемодинаміки у період раннього відновлення після різних режимів фізичного навантаження

We studied the changes in central hemodynamics in the early recovery period after physical load in 28 young men. Dynamic loading was induced using a modified Martine functional test, static loading - by maintaining on the standing dynamometer DS-200 muscle effort in the amount of 50% of maximum standing force. The change in central hemodynamic para- meters was recorded by tetrapolar thoracic impedance rheo- plethysmogram using a computerized diagnostic complex «Cardio +». Dynamic exercise during early recovery did not lead to a significant increase in heart rate, however, it caused a decrease in the resistance of resistive blood vessels and an increase in pulse blood pressure. The increase in minute blood volume in our study is mainly due to an increase in stroke volume, pointing for high functional reserves of the heart. In the case of static physical activity, the adaptive reactions of central hemodynamics and the course of the processes of early recovery of the circulatory system are radically different from similar indicators during dynamic physical activity. In subjects with a normodynamic type of response of the cardiovascular system to dynamic load, no significant changes in the minute volume of blood flow were registered at a similar volume of active muscle mass static load. In subjects with a normodynamic type of cardiovascular response to dynamic load, no significant changes in cardiac output were observed at a similar static load in terms of active muscle mass. However, during early recovery period, the total peripheral vascular resistance and systolic arterial pressure were increased. The increase in total peripheral resistance may be due to reactive hyperemia in ischemic skeletal muscle caused by increased blood flow to the capillaries after muscle relaxation and delayed outflow into the veins. The significant increase in systolic blood pressure can be explained by the mechanical obstruction of blood flow in the muscle capillaries during prolonged static contraction.

Correlation between Fibrinogen Level with Middle Cerebral Artery Pulsatility Index in Acute Ischemic Stroke

Background: High levels of fibrinogen will increase the blood viscosity. Pulsatility index parameter intranscranial doppler can measure blood vessel resistance which influence by cerebral blood flow velocityand blood viscosity. This study has aim to find correlation between fibrinogen with PI in acute thromboticstroke patient.Method: A cross sectional design was used in this study. The samples were patient with acute ischemic strokein neurological ward Dr. Soetomo Hospital Surabaya from January 2019 to December 2020. Fibrinogenlevel was measured using clauss method. PI was calculated by peak systolic velocity, end diastolic velocityand mean vessel velocity, which were measured in middle cerebral artery.Result: This study involved 32 samples consisted 22 males and 10 females. Mean age of subjects was55.37 ± 10.55. The mean fibrinogen level is 356.95 ± 139.57. Mean MCA PI is 1.03 ±0.34. There is positivecorrelation with weak correlation strength between fibrinogen level with MCA PI in acute thrombotic strokepatients and statistically significant (p=0.024, r=0.398).Conclusion: There is a positive correlation between fibrinogen level with PI MCA in acute thromboticstroke.

Modulation of vascular contraction via soluble guanylate cyclase signaling in a novel ex vivo method using rat precision-cut liver slices.

Fibrotic processes in the liver of non‐alcoholic steatohepatitis (NASH) patients cause microcirculatory dysfunction in the organ which increases blood vessel resistance and causes portal hypertension. Assessing blood vessel function in the liver is challenging, necessitating the development of novel methods in normal and fibrotic tissue that allow for drug screening and translation toward pre‐clinical settings. Cultures of precision cut liver slices (PCLS) from normal and fibrotic rat livers were used for blood vessel function analysis. Live recording of vessel diameter was used to assess the response to endothelin‐1, serotonin and soluble guanylate cyclase (sGC) activation. A cascade of contraction and relaxation events in response to serotonin, endothelin‐1, Ketanserin and sGC activity could be established using vessel diameter analysis of rat PCLS. Both the sGC activator BI 703704 and the sGC stimulator Riociguat prevented serotonin‐induced contraction in PCLS from naive rats. By contrast, PCLS cultures from the rat CCl4 NASH model were only responsive to the sGC activator, thus establishing that the sGC enzyme is rendered non‐responsive to nitric oxide under oxidative stress found in fibrotic livers. The role of the sGC pathway for vessel relaxation of fibrotic liver tissue was identified in our model. The obtained data shows that the inhibitory capacities on vessel contraction of sGC compounds can be translated to published preclinical data. Altogether, this novel ex vivo PCLS method allows for the differentiation of drug candidates and the translation of therapeutic approaches towards the clinical use.

Monoaminergic Receptors as Modulators of the Perivascular Sympathetic and Sensory CGRPergic Outflows.

Blood pressure is a highly controlled cardiovascular parameter that normally guarantees an adequate blood supply to all body tissues. This parameter is mainly regulated by peripheral vascular resistance and is maintained by local mediators (i.e., autacoids), and by the nervous and endocrine systems. Regarding the nervous system, blood pressure can be modulated at the central level by regulating the autonomic output. However, at peripheral level, there exists a modulation by activation of prejunctional monoaminergic receptors in autonomic- or sensory-perivascular fibers. These modulatory mechanisms on resistance blood vessels exert an effect on the release of neuroactive substances from the autonomic or sensory fibers that modify blood pressure. Certainly, resistance blood vessels are innervated by perivascular: (i) autonomic sympathetic fibers (producing vasoconstriction mainly by noradrenaline release); and (ii) peptidergic sensory fibers [producing vasodilatation mainly by calcitonin gene-related peptide (CGRP) release]. In the last years, by using pithed rats, several monoaminergic mechanisms for controlling both the sympathetic and sensory perivascular outflows have been elucidated. Additionally, several studies have shown the functions of many monoaminergic auto-receptors and hetero-receptors expressed on perivascular fibers that modulate neurotransmitter release. On this basis, the present review: (i) summarizes the modulation of the peripheral vascular tone by adrenergic, serotoninergic, dopaminergic, and histaminergic receptors on perivascular autonomic (sympathetic) and sensory fibers, and (ii) highlights that these monoaminergic receptors are potential therapeutic targets for the development of novel medications to treat cardiovascular diseases (with some of them explored in clinical trials or already in clinical use).

Baroreceptor denervation reduces inflammatory status but worsens cardiovascular collapse during systemic inflammation

Beyond the regulation of cardiovascular function, baroreceptor afferents play polymodal roles in health and disease. Sepsis is a life-threatening condition characterized by systemic inflammation (SI) and hemodynamic dysfunction. We hypothesized that baroreceptor denervation worsens lipopolysaccharide (LPS) induced-hemodynamic collapse and SI in conscious rats. We combined: (a) hemodynamic and thermoregulatory recordings after LPS administration at a septic-like non-lethal dose (b) analysis of the cardiovascular complexity, (c) evaluation of vascular function in mesenteric resistance vessels, and (d) measurements of inflammatory cytokines (plasma and spleen). LPS-induced drop in blood pressure was higher in sino-aortic denervated (SAD) rats. LPS-induced hemodynamic collapse was associated with SAD-dependent autonomic disbalance. LPS-induced vascular dysfunction was not affected by SAD. Surprisingly, SAD blunted LPS-induced surges of plasma and spleen cytokines. These data indicate that baroreceptor afferents are key to alleviate LPS-induced hemodynamic collapse, affecting the autonomic control of cardiovascular function, without affecting resistance blood vessels. Moreover, baroreflex modulation of the LPS-induced SI and hemodynamic collapse are not dependent of each other given that baroreceptor denervation worsened hypotension and reduced SI.

INTERDISCIPLINARY INTEGRATION IN A MEDICAL UNIVERSITY: PROPEDEUTICS OF INTERNAL DISEASES AND MEDICAL AND BIOLOGICAL PHYSICS.

This paper highlights the issues on interdisciplinary integration of the disciplines as the propedeutics of internal diseases and medical and biological physics studied by students of medical and dental faculties. It has been shown that the integration of these disciplines is the most pronounced when studying acoustic wave methods of investigation in the clinical practice; hydro- and hemodynamics and their role in diagnosing the cardiovascular diseases, and, in particular the rheological properties of blood, the hydraulic resistance of blood vessels. Considerable attention is paid to explaining the physical basics of electrocardiography. Acoustic wave investigation techniques in the clinical practice, percussion and auscultation first and foremost are very important test-timed techniques, especially when diagnosing the broncho-pulmonary system. While studying the propedeutics of internal diseases, students acquire concepts for applying the percussion and analysing the characteristic sounds heard: the principle of resonance, the percussion sphere. The medical students’ ability to understand the mechanisms of changes that occur in certain pathologies creates the basis for a deeper analysis of the dynamics of these processes. Students analyze the characteristics of sounds and noises of varying intensity, which are created by tissues of different density, by airless organs in response to the amplification of percussion sounds. When studying the auscultation technique, the students acquire knowledge and skills to differentiate sounds, tones and noises produced by the functioning of internal organs. The section of medical and biological physics devoted to hydro- and hemodynamics is important for stronger understanding the blood circulation through the cardiovascular system in the human body and for diagnosing and treating diseases of this system. Students will learn about the causes of turbulent flow, functional and organic noise in the heart area and their connection with the phases of cardiac activity. The article has also demonstrated the integration of the physical fundamentals of electrocardiography into practical medicine.

Sympathetic Neurotransmission in Resistance Mesenteric Arteries in Obesity‐Related Hypertension

Hyperactivity of sympathetic nerves has an important role in the pathogenesis of obesity‐related hypertension. The mechanisms linking obesity to hypertension are unclear. Small mesenteric arteries (MA, &lt;300 mm dia.) are resistance blood vessels that are densely innervated by sympathetic nerves. Nerve varicosities release norepinephrine (NE) and ATP which cause arterial constriction. Impaired control of NE and/or ATP release and clearance would cause hypertension. Alterations in sympathetic nerves supplying MAs contribute to hypertension in several animal models. This study examined whether alterations of sympathetic neurotransmission in the resistance MAs contribute to high blood pressure in high fat‐fed (HF) Dahl salt‐sensitive rats. Sympathetic nerves supplying MAs maintained in vitro were stimulated focally. Electrically‐evoked NE and ATP release were detected by using amperometry with carbon fiber electrodes, and intracellular recording of excitatory junction potentials (EJPs) from arterial smooth muscle cells, respectively. Data were obtained from male and female rats at 10, 17, and 24 weeks of control and HF diet. Peak amplitudes of NE oxidation current and EJPs were assessed. NE oxidation current from all groups were blocked by a Na+ channel blocker, tetrodotoxin (TTX, 300 nM), suggesting that NE release in neurogenic. EJPs from all groups were abolished by TTX, and PPADS (10 μM), a P2X receptor antagonist, indicating that EJPs were neurogenic and purinergic. Frequency (1–30 Hz, 50 pulses) response curves using amperometric measurement of NE release showed similar responses in MAs from control and HF fed male and female rats. EJP frequency (0.5–10Hz, 5 pulses) response curves were also similar in MA from control and HF fed male and female rats. We investigated prejunctional α2‐adrenergic receptor function using the α2 receptor agonist (UK14,304) and antagonist (yohimbine). UK14,304 (0.0001–10 μM) inhibited NE and ATP release equally well and in a concentration‐dependent manner in MAs from control and HF rats. In the presence of 1 μM yohimbine, NE and ATP release was increased equally in MA from all rats. We conclude that adrenergic and purinergic neurotransmission by periarterial sympathetic nerves are not affected in HF Dahl salt sensitive rats. Elevated blood pressure in this animal model is not dependent on altered sympathetic neurotransmission to the mesenteric vasculature.Support or Funding InformationNIH 2P01HL070687 (For JJG), and Post‐doctoral training scholarship, Faculty of Medicine, Thammasat University, Thailand (For SS).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Hemodynamics in experimental acute myocardial ischemia against the background of the use of substance PK-66 in comparison with the cordarone

The aim of the study was to study the effect of PK-66 substances on hemodynamic parameters under experimental acute myocardial ischemia compared with cordarone.Materials and methods. The experiments were carried out on 21 rabbits of the chinchilla breed. Acute myocardial ischemia (AMI) was modeled by intravenous injection of epinephrine at a dose of 0.2 mg / kg and caffeine sodium benzoate at a dose of 25 mg / kg. In the studies carried out, the Cordarone compounds and the PC-66 test sample were used. The maximum pressure in the left ventricle (MPLV), mean arterial pressure (MAP), total peripheral vascular resistance (TPVR), and minute volume (MV) were recorded. The initial values of the parameters studied were recorded immediately after the administration and after 30 minutes. after administration of the test substance, immediately after the introduction of the analyzers, and also after 15 and 30 minutes. after modeling pathology.Results Simulation of AMI in rabbits, accompanied by a decrease in MV, caused by a decrease in contractile activity of the myocardium, also showed a simultaneous decrease MPLV in and a significant increase in TPVR, which is caused by a sudden decrease in MV and a decrease in MAP. The introduction of cordarone reduces the changes observed in the modeling of pathology (6.33–10.36 %). The use of PK-66 neutralizes changes in maximum pressure in the left ventricle observed immediately after modeling AMI, followed by a decrease in this parameter after 15 minutes. and normalization after 30 minutes. The prophylactic administration of the PK-66 test sample did not significantly influence the modeling of AMI. Substance PK-66 and cordarone showed a close unidirectional effect in AMI, reducing the changes in SAT, MPLV, MAP, and TPVR in pathology.Conclusions. Acute ischemia of the myocardium in rabbits is characterized by an increase: total peripheral resistance of blood vessels, a decrease in the minute volume of blood and systolic blood pressure. Prophylactic administration of PK-66 leads to normalization of indicators of general hemodynamics in AMI, not inferior in effectiveness to the drug comparison kordaronu.

Proof of Principle for a Novel Class of Antihypertensives That Target the Oxidative Activation of PKG Iα (Protein Kinase G Iα).

Arterial hypertension continues to be a major health burden. Development of new antihypertensive drugs that engage vasodilatory mechanisms not harnessed by available therapies offer therapeutic potential. Oxidants induce an interprotein disulfide in PKG Iα (protein kinase G Iα) at C42, which is associated with its targeting and activation, resulting in vasodilation and blood pressure lowering. Consequently, we developed an assay and screened for electrophilic drugs that activate PKG Iα by selectively targeting C42, as such compounds have potential as novel antihypertensives with a mechanism of action that differs from current therapies. In this way, a drug that we termed G1 was identified, which targets C42 of PKG Iα to induce vasodilation of isolated resistance blood vessels and blood pressure lowering in a mouse model of angiotensin II-induced hypertension. In contrast, these antihypertensive effects were deficient in angiotensin II-induced hypertensive C42S PKG Iα knockin mice. These transgenic mice were engineered to have the reactive cysteinyl thiol replaced with a hydroxyl so that it cannot react with endogenous vasodilatory oxidants or electrophiles such as drug G1. These studies, therefore, provide validation of PKG Iα C42 as the target of G1, as well as proof-of-principle for a new class of antihypertensive drugs that have potential for further development for clinical use in humans.