Blood Pressure Volume Research Articles

Drug Interaction of SGLT2Is and ARNI on Acute Kidney Injury: A Real-World Pharmacovigilance Analysis Through the FAERS.

Sodium-glucose cotransporter 2 inhibitors (SGLT2Is) and angiotensin receptor-neprilysin inhibitor (ARNI) may cause potential renal damage, the combined impact of SGLT2Is and ARNI on acute kidney injury (AKI) remains unclear. This pharmacovigilance study conducted a disproportionality analysis using reports from the FDA Adverse Event Reporting System database. The reporting odds ratio was used as an estimate for detecting AKI signal. A total of 659,573 reports on at least 1 glucose-lowering drug and/or ARNI were obtained. Of the 413 reports on cotherapy of SGLT2Is and ARNI, 99 (24.0%) reports mentioned AKI. Overall, the AKI reporting rate significantly increased in cotherapy (adjusted reporting odds ratio, 95% confidence interval: 8.04, 6.20-10.42, P < 0.001), with a stronger AKI signal in cotherapy of canagliflozin and ARNI (16.82, 3.75-75.57, P < 0.001). Specifically, no increased AKI signal was detected in patients with heart failure (HF) receiving cotherapy after adjustment for sex and age (HF: 1.27, 0.89-1.80, P = 0.189; HF plus diabetes: 2.08, 0.99-4.40, P = 0.055; or HF plus hypertension: 1.69, 0.53-5.35, P = 0.376), whereas enhanced AKI signals were detected in patients with diabetes (20.57, 11.93-35.46, P < 0.001), hypertension (4.30, 1.98-9.37, P < 0.001), or diabetes plus hypertension (5.44, 1.92-15.43, P = 0.001). This study reveals that superimposed renal impairment results from cotherapy with SGLT2Is and ARNI. It is necessary to be vigilant that the elderly patients with diabetes, hypertension, or chronic kidney disease are more susceptible to AKI, especially if they likewise receive diuretics. When cotherapy is unavoidable, early monitoring of renal function, blood volume, and blood pressure is excessively crucial. However, it is relatively safe in patients with HF.

105 Fetal hypothyroidism dysregulates local hepatic and renal renin-angiotensin systems in a temporal manner

Abstract The renin-angiotensin system (RAS) is an essential endocrine system with roles in electrolyte balance, blood volume, and blood pressure. While the canonical RAS exerts systemic vasoregulatory effects through steps involving hepatic, renal, and pulmonary-derived compounds, there is also evidence of localized, independently acting RAS in organs such as the liver and kidney. Further, modulations in RAS resulting from fetal hypothyroidism have previously been documented, although the temporal specificity of this endocrine interaction is not well-characterized. Thus, the objective of the current study was to examine the time-dependency of modulations in local hepatic and renal RAS in a porcine model of fetal hypothyroidism. To achieve this, pregnant gilts (n = 24) were divided evenly into either a control (CON) or methimazole (MMI) treatment group, with the MMI group receiving 5 mgּ kg-1ּ d-1 of oral MMI treatment and the CON group receiving an equivalent sham carrier. Each group was further divided into four timepoints (n = 3/treatment at each timepoint), with treatment beginning on d 34, 45, 55, or 65 of gestation. After 21 d of treatment, and at d 55, 66, 76, and 86, respectively, the gilts were humanely euthanized, blood samples taken from all fetuses (n = 340), and thyroid, liver (LVR), and kidney (KID) collected from a subset of four fetuses per litter (n = 96). Confirmation of fetal hypothyroidism in the MMI group was accomplished via histological assessment of the thyroid and measurement of circulating thyroxine (T4) concentrations. Each MMI-treated fetus (n = 96) subset showed evidence of goitrous thyroid histology, with the absence of healthy eosinophilic colloid indicating successful disruption of the fetal hypothalamic-pituitary-thyroid axis. T4 assays performed on a similar subset of n = 96 fetuses showed that MMI treatment significantly reduced T4 concentrations within each timepoint relative to CON (P &amp;lt; 0.001 at all timepoints). Following confirmation of hypothyroidism, RNA was extracted from the fetal LVR and KID samples to allow for gene expression analysis by qPCR. Ct values were normalized, fold changes calculated using the 2-∆∆Ct method, and differences within timepoint determined using a Wilcoxon signed-rank test. AGT, the precursor to all bioactive RAS peptides, was significantly downregulated in LVR at d 66 (P = 0.014) and 76 (P &amp;lt; 0.001). ACE was significantly upregulated at d 76 in both LVR (P = 0.037) and KID (P = 0.005). No significant changes were observed for ACE2 in either tissue, or for renal REN. Finally, AGTR1, the receptor that mediates RAS effects, was significantly downregulated at d 55 in KID (P &amp;lt; 0.001) and d 76 in LVR (P = 0.023), while also being upregulated at d 86 in LVR (P = 0.033). Collectively, these results show that fetal hypothyroidism modulates RAS function in a gestational age-dependent manner, which may alter fetal development and subsequent postnatal physiology.

The effect of long-term hemodialysis on diabetic retinopathy observed by swept-source optical coherence tomography angiography

BackgroundDiabetes can cause chronic microvascular complications such as diabetic retinopathy (DR) and diabetic nephropathy (DN). DR and DN can lead to or exacerbate diabetic macular edema (DME). Hemodialysis (HD) is the main treatment method for patients with end-stage kidney disease (ESKD) secondary to DN.PurposeThe aim of this prospective cohort study was to determine the immediate effect of single HD session on retinal and choroidal thickness in DR patients with ESKD and the features of DR and the prevalence of DME in these patients who have received long-term HD.MethodsEighty-five eyes of 44 DR patients with ESKD who underwent long-term HD were examined by swept-source optical coherence tomography angiography (SS-OCTA). Based on OCTA images, the characteristics of DR and the prevalence of DME in these patients were analyzed. Changes in central retinal thickness (CRT), central retinal volume (CRV), subfoveal choroidal thickness (SFCT) and subfoveal choroidal volume (SFCV) within 30 min before and after single HD session were compared. CRT, CRV, SFCT and SFCV were compared before single HD session and before the next single HD session.ResultsThere was no significant difference in the average CRT (251.69 ± 39.21 μm vs. 251.46 ± 39.38 μm, P = 0.286) or CRV (0.15 ± 0.62 μm vs. 0.15 ± 0.63 μm, P = 0.324) between before and after single HD session. After single HD session, SFCT (243.11 ± 77.15 μm vs. 219.20 ± 72.84 μm, P < 0.001) and SFCV (0.15 ± 0.10 μm vs. 0.13 ± 0.90 μm, P < 0.001) significantly decreased. There was no statistically significant difference in CRT (251.69 ± 39.21 μm vs. 251.11 ± 38.47 μm, P = 0.206), CRV (0.15 ± 0.62 μm vs. 0.15 ± 0.61 μm, P = 0.154), SFCT (243.11 ± 77.15 μm vs. 245.41 ± 76.23 μm, P = 0.108), or SFCV (0.15 ± 0.10 μm vs. 0.16 ± 0.10 μm, P = 0.174) before HD and before the next single HD session. On en face OCTA images, eighty-five eyes (100%) had retinal nonperfusion areas, foveal avascular zone (FAZ) enlargement, and abnormal retinal microvasculature. Based on cross-sectional OCTA images, retinal neovascularization (RNV) was confirmed in 42 eyes (49.41%), and intraretinal microvascular abnormalities (IRMAs) were detected in 85 eyes (100%). Seventeen eyes (20%) still had DME, all of which were cystoid macular edema (CME). Among eyes with DME, the epiretinal membrane (ERM) was present in 7 eyes (8.24%).ConclusionsFor DR patients with ESKD who have undergone long-term HD, the choroidal thickness still changes significantly before and after single HD session, which may be related to short-term effects such as reduced blood volume and plasma osmotic pressure caused by single HD session. Although macular features seem to have stabilized in DR patients undergoing long-term dialysis, the DR of patients with ESKD should still be given attention.

EEG and Physiological Signals Dataset from Participants during Traditional and Partially Immersive Learning Experiences in Humanities

The relevance of the interaction between Humanities-enhanced learning using immersive environments and simultaneous physiological signal analysis contributes to the development of Neurohumanities and advancements in applications of Digital Humanities. The present dataset consists of recordings from 24 participants divided in two groups (12 participants in each group) engaging in simulated learning scenarios, traditional learning, and partially immersive learning experiences. Data recordings from each participant contain recordings of physiological signals and psychometric data collected from applied questionnaires. Physiological signals include electroencephalography, real-time engagement and emotion recognition calculation by a Python EEG acquisition code, head acceleration, electrodermal activity, blood volume pressure, inter-beat interval, and temperature. Before the acquisition of physiological signals, participants were asked to fill out the General Health Questionnaire and Trait Meta-Mood Scale. In between recording sessions, participants were asked to fill out Likert-scale questionnaires regarding their experience and a Self-Assessment Manikin. At the end of the recording session, participants filled out the ITC Sense of Presence Inventory questionnaire for user experience. The dataset can be used to explore differences in physiological patterns observed between different learning modalities in the Humanities.

Daily use of veno-constrictive thigh cuffs during 30 days of strict 6° head-down tilt bedrest to reverse the headward fluid shift

Introduction: Chronic exposure to weightlessness induces a persistent headward fluid shift, which may contribute to the development of Spaceflight Associated Neuro-ocular Syndrome (SANS). Strict 6° head-down tilt bedrest (HDTBR) is a spaceflight analog that induces a headward fluid shift and development of SANS findings, enabling the evaluation of potential countermeasures. Lower body exercise can induce a sustained post-exercise hyperemia thereby shifting blood away from the central circulation. In addition, veno-constrictive thigh cuffs (VTC) can sequester blood volume in the legs. The purpose of this study was to determine whether 6 hours of daily VTC use following cycling exercise (Ex+VTC) could reverse the headward fluid shift during 30 days of strict 6° HDTBR. We hypothesized that Ex+VTC would sequester fluid in the legs leading to increased thigh circumference and reduced stroke volume (SV), cardiac output (CO), internal jugular vein (IJV) cross-sectional area (CSA) and pressure, and intraocular pressure (IOP). Methods: Participants were randomly assigned to a Control (n=12, 6 female) or Ex+VTC (n=12, 4 female) group and completed baseline data collection (BDC) in the seated and supine posture followed by 30 days of strict 6° HDTBR. The Ex+VTC group completed a maximal exercise test on a cycle ergometer in 6° HDT posture during BDC to establish work rates during HDTBR. The Ex+VTC group performed 10 minutes of light cycle exercise, cycled for 45 minutes at 45% of their max wattage, and then donned VTC to ~50 mmHg for 6 hours on 6 of 7 days per week during HDTBR. Data were collected before exercise and 30 minutes and 6 hours after exercise and donning VTCs on days 3, 17, and 29 of HDTBR. Controls were studied at similar time points. Days were nested within the models. Mixed models were used to determine differences between groups in the change in thigh circumference measured using a flexible tape measure, bilateral IOP measured using tonometry, CO measured using the inert gas rebreathe technique (Innocor), and ultrasound of bilateral IJV CSA and pressure from before to 30 min and 6 hours after use of the countermeasure. Left and right IJV and IOP data were nested within each participant. Results: The Ex+VTC group completed all exercise sessions followed by 6 hours of VTC use. Compared to Control, thigh circumference was greater after 30 minutes (+1.3 vs. -0.2 cm, p&lt;0.001) and 6 hours of VTC use (+2.5 cm vs. -0.1 cm in controls, p&lt;0.001). SV (-38 vs. 2 ml, p&lt;0.001) and CO (-1.5 vs. 0.3 L/min, p&lt;0.001) were reduced at 30 minutes and 6 hours of VTC use (SV: -30 vs. 5 ml, p&lt;0.001; CO: -1.1 vs. 0.6 L/min, p&lt;0.001) compared to Control. IJV CSA and pressure were reduced at 30 minutes (CSA, p&lt;0.001; pressure, p=0.001) and 6 hours of VTC use (CSA, p&lt;0.001; pressure, p=0.007). IOP was not different compared to Control. Conclusions:Use of VTC for 6 hours after 45 minutes of exercise successfully sequestered fluid in the legs, leading to a reduction in central blood volume, IJV CSA, and IJV pressure. Thus, an Ex+VTC countermeasure resulted in a partial fluid shift reversal. This research was supported by the NASA Human Research Program. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The role of CCN1 in kidney-brain crosstalk

Cognitive impairment and dementia are major global health problems of the aging human population. It is estimated that about 55 million people were living with dementia in 2019 and this number is expected to triple by 2050. Dementia can result from abnormal structure and function of brain blood vessels that may develop in a variety of conditions including chronic kidney disease (CKD). Recent studies from our laboratory suggest that in addition to controlling blood volume and blood pressure (renin), and blood cell count (erythropoietin), the kidney produces novel systemic angiogenic hormones to maintain blood vessels, such as the matricellular protein Cellular Communication Network factor 1 (CCN1). These hormones are then released to the blood and may act as new molecular mechanisms of kidney-brain crosstalk. We hypothesized that kidney-derived CCN1 helps to preserve the normal structure and function of blood vessels throughout the body, including a healthy blood-brain barrier (BBB). We further hypothesized that reduced plasma CCN1 caused by diminished renal production of CCN1 due to kidney disease plays a major role in the development of brain vascular dysfunction, and therefore in the pathogenesis and progression of dementia and cognitive impairment. Intravital multiphoton (MPM) imaging of the intact mouse brain in control or after 5/6 nephrectomy (5/6 Nx), a well-established mouse model of chronic kidney disease (CKD) was used to measure changes in BBB permeability with or without chronic CCN1 treatment. Kidney and BBB structure/function phenotyping was performed using CCN1 ELISA assay, the Medibeacon transdermal GFR measurement system, tissue harvest, and immunohistochemistry. Compared to control, 5/6 Nx mice had reduced plasma CCN1 levels, reduced GFR, but no difference in systolic blood pressure. MPM imaging showed increased fluorescence intensity of mid-size plasma proteins (A680 conjugated Albumin 70 kDa) compared to high molecular weight markers (A488 conjugated Dextran 500 kDa) in brain interstitium in 5/6 Nx compared to control. In addition, the density of cell-to-cell junctions in brain endothelial cells were 20% reduced in CKD compared to control healthy mice. In brain endothelial cells cultured in vitro, CCN1 treatment had protective effects on cell proliferation, motility and angiogenesis as confirmed by scratch and tube formation assays. In summary, this study identified new mechanisms of kidney-brain crosstalk, and helped to improve our mechanistic understanding of cerebrovascular pathology in CKD. DK123564, DK064324, DK135290. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Self-regulation training improves stress resilience in elite pre-pubescent female gymnasts.

In the context of young female athletes, namely elite gymnasts, effective stress management strategies not only enhance performance, but also reduce the risk of injuries and promote overall well-being. This study aims to investigate the effects of biofeedback-based training on stress management in prepubescent elite female gymnasts, recognizing its pivotal role in promoting healthy growth and proper training load management. Eight elite young female athletes from a top flight French national league club participated in an experimental condition involving four-week biofeedback training program to improve self-regulation skills, during both rest and stress phases. Additionally, each subject experienced a control condition, with entailed exposure to domain-specific motivational videos. Comprehensive evaluations of physiological parameters were conducted to assess the impact of biofeedback training, both before and after the training, as well as during the stress and recovery phases. Furthermore, an interoceptive body awareness test, using the MAIA questionnaire, was performed. The results highlight a significant enhancement of the self-regulatory skills of the gymnasts in managing the selected physiological parameters-peripheral temperature (p < 0.05) and blood volume pressure (p < 0.05)-after the biofeedback treatment. Moreover, psychological data from the MAIA questionnaire revealed a noteworthy increase in interoceptive awareness (p < 0.001), particularly in the subscales of Not Distracting (p < 0.001), Attention regulation (p < 0.05), Emotional awareness (p < 0.05), and Self-regulation (p < 0.05). Thus, we conclude that biofeedback training improves self-regulatory and psychological resilience under stressful conditions, while reducing sensitivity to gymnastics-specific stress.

Quantitative analysis of similarity between cerebral arterial blood volume and intracranial pressure pulse waveforms during intracranial pressure plateau waves

IntroductionBoth intracranial pressure (ICP) and cerebral arterial blood volume (CaBV) have a pulsatile character related to the cardiac cycle. The evolution of the shape of ICP pulses under increasing ICP or decreasing intracranial compliance is well documented. Nevertheless, the exact origin of the alterations in the ICP morphology remains unclear. Research questionDoes ICP pulse waveform become similar to non-invasively estimated CaBV pulse during ICP plateau waves. Material and methodsA total of 15 plateau waves recorded in 15 traumatic brain injured patients were analyzed. CaBV pulse waveforms were calculated using global cerebral blood flow model from transcranial Doppler cerebral blood flow velocity (CBFV) signals. The difference index (DI) was used to quantify the similarity between ICP and CaBV waveforms. DI was calculated as the sum of absolute sample-by-sample differences between ICP and CaBV waveforms, representing the area between the pulses. ResultsICP increased (19.4 mm Hg [Q1–Q3: 18.2–23.4 mm Hg] vs. 42.7 mm Hg [Q1–Q3: 36.5–45.1 mm Hg], p < 0.001) while CBFV decreased (44.2 cm/s [Q1–Q3: 34.8–69.5 cm/s] vs. 32.9 cm/s [Q1–Q3: 24.7–68.2 cm/s], p = 0.002) during plateau waves. DI was smaller during the plateau waves (20.4 [Q1–Q3: 15.74–23.0]) compared to the baselines (26.3 [Q1–Q3: 24.2–34.7], p < 0.001). Discussion and conclusionThe area between corresponding ICP and CaBV pulse waveforms decreased during the plateau waves which suggests they became similar in shape. CaBV may play a significant role in determining the shape of ICP pulses during the plateau waves and might be a driving force in formulating ICP elevation.

Gaseous Micro-Embolic Activity and Goal-Directed Perfusion Management in a Closed System for Cardiopulmonary Bypass and Minimally Invasive Extracorporeal Circulation during Coronary Artery Bypass Grafting.

Cardiopulmonary bypass (CPB) techniques are becoming minimally invasive in clinical practice. The literature describes various extracorporeal techniques which seek to eliminate air-blood contact and reduce both hemodilution and the contact surface such as in Minimally invasive Extracorporeal Circulation (MiECC) and closed systems for CPB. However, the delivery of micro-embolic activity in the circuit and metabolic activity in terms of oxygen delivery for Goal-Directed Perfusion (GDP) management, in relation to the patient's blood volume and central venous pressure, have never been related and correlated. In this report, we present a cohort study that investigated these aspects between the closed SVR2000 System and modular MiECC (both from Eurosets SRL, Medolla, Italy). Data were collected retrospectively and used to compare 60 consecutive patients who underwent isolated coronary artery bypass grafting (CABG) surgery by two surgeons using an SVR2000 oxygenator in 30 procedures, with a matched cohort of patients from the same period who underwent isolated CABG surgery by two other surgeons using a modular MiECC in 30 procedures. The primary endpoints collected were data on micro-embolic activity, including the number of gaseous micro-emboli in the circuit during the procedure, the mean maintenance value of oxygen delivery (DO2) and data relating to venous return volume and central venous pressure (CVP). During the CPB procedures, the following values were recorded for the closed SVR2000 and MiECC groups, respectively: the average number of gaseous micro-emboli (GME) in the venous line, 833 ± 23 vs 1221 ± 45 (p = 0.028); GME in the outlet of the pump, 375 ± 45 vs 429 ± 76 (p = 0.89; GME in the arterial line, 189 ± 36 vs 205 ± 27 (p = 0.92), and the volume of GME in the arterial line (mL), 0.32± 12 vs 0.49± 17 (p = 0.93). The mean Indexed Oxygen Delivery (DO2i) during cross-clamp (ml/min/m2) was 319 ±12 vs 278 ±9 (p = 0.0019), respectively. The maximum mean volume of venous return in the soft-shell venous reservoir (ml) was 1801 ±128 vs 824 ±192 (p = 0.038). The mean central venous pressure (CVP) during cross-clamp (mmHg) was 0 ± 2 vs 6 ± 2 (p = 0.019). In this study, the results in the closed SVR2000 group were not statistically inferior to those in the modular MiECC group in terms of gaseous micro-embolic activity during CPB. Our analysis showed an important reduction of GME delivery in both systems. The closed SVR2000 group showed better management for GDP in terms of DO2i, associated with the flexibility of dynamic volume management and the absence of cavitation and regulation of the rate per minute and pump flow, which were reported in the MiECC group. The SVR2000 and modular MiECC systems were both safe and effective in perioperative practice without iatrogenic problems.

Emotion Recognition from Physiological Signals Collected with a Wrist Device and Emotional Recall.

Implementing affective engineering in real-life applications requires the ability to effectively recognize emotions using physiological measurements. Despite being a widely researched topic, there seems to be a lack of systems that translate results from data collected in a laboratory setting to higher technology readiness levels. In this paper, we delve into the feasibility of emotion recognition beyond controlled laboratory environments. For this reason, we create a minimally-invasive experimental setup by combining emotional recall via autobiographical emotion memory tasks with a user-friendly Empatica wristband measuring blood volume pressure, electrodermal activity, skin temperature, and acceleration. We employ standard practices of feature-based supervised learning and specifically use support vector machines to explore subject dependency through various segmentation methods. We collected data from 45 participants. After preprocessing, using a data set of 134 segments from 40 participants, the accuracy of the classifier after 10-fold cross-validation was barely better than random guessing (36% for four emotions). However, when extracting multiple segments from each emotion task per participant using 10-fold cross-validation (i.e., including subject-dependent data in the training set), the classification rate increased to up to 75% for four emotions but was still as low as 32% for leave-one-subject-out cross-validation (i.e., subject-independent training). We conclude that highly subject-dependent issues might pose emotion recognition.

The geometry of synchronization: quantifying the coupling direction of physiological signals of stress between individuals using inter-system recurrence networks.

In the study of synchronization dynamics between interacting systems, several techniques are available to estimate coupling strength and coupling direction. Currently, there is no general 'best' method that will perform well in most contexts. Inter-system recurrence networks (IRN) combine auto-recurrence and cross-recurrence matrices to create a graph that represents interacting networks. The method is appealing because it is based on cross-recurrence quantification analysis, a well-developed method for studying synchronization between 2 systems, which can be expanded in the IRN framework to include N > 2 interacting networks. In this study we examine whether IRN can be used to analyze coupling dynamics between physiological variables (acceleration, blood volume pressure, electrodermal activity, heart rate and skin temperature) observed in a client in residential care with severe to profound intellectual disabilities (SPID) and their professional caregiver. Based on the cross-clustering coefficients of the IRN conclusions about the coupling direction (client or caregiver drives the interaction) can be drawn, however, deciding between bi-directional coupling or no coupling remains a challenge. Constructing the full IRN, based on the multivariate time series of five coupled processes, reveals the existence of potential feedback loops. Further study is needed to be able to determine dynamics of coupling between the different layers.

Processing Ultrasound Scans of the Inferior Vena Cava: Techniques and Applications.

The inferior vena cava (IVC) is the largest vein in the body. It returns deoxygenated blood to the heart from the tissues placed under the diaphragm. The size and dynamics of the IVC depend on the blood volume and right atrial pressure, which are important indicators of a patient's hydration and reflect possible pathological conditions. Ultrasound (US) assessment of the IVC is a promising technique for evaluating these conditions, because it is fast, non-invasive, inexpensive, and without side effects. However, the standard M-mode approach for measuring IVC diameter is prone to errors due to the vein movements during respiration. B-mode US produces two-dimensional images that better capture the IVC shape and size. In this review, we discuss the pros and cons of current IVC segmentation techniques for B-mode longitudinal and transverse views. We also explored several scenarios where automated IVC segmentation could improve medical diagnosis and prognosis.

Regulation of the renin-angiotensin-aldosterone system by cyclic nucleotides and phosphodiesterases.

The renin-angiotensin-aldosterone system (RAAS) is one of the key players in the regulation of blood volume and blood pressure. Dysfunction of this system is connected with cardiovascular and renal diseases. Regulation of RAAS is under the control of multiple intracellular mechanisms. Cyclic nucleotides and phosphodiesterases are the major regulators of this system since they control expression and activity of renin and aldosterone. In this review, we summarize known mechanisms by which cyclic nucleotides and phosphodiesterases regulate renin gene expression, secretion of renin granules from juxtaglomerular cells and aldosterone production from zona glomerulosa cells of adrenal gland. We also discuss several open questions which deserve future attention.

Overweight and dysregulation of the autonomic nervous system in young persons

Background. More than 1 billion people worldwide are obese, and this number is growing. Obesity at an early age is accompanied by impaired carbohydrate tolerance and the development of type 2 diabetes, lipid metabolism pathology, obstructive apnea, hypercoagulability, chronic inflammation and the development of insulin resistance in the future. In modern literature, there is no single point of view regarding the role of the autonomic nervous system in the coordination of hormonal, nervous and metabolic factors in the body.Aim. The article presents the results of studying the functional state of the sympathetic and parasympathetic parts of the autonomic nervous system in overweight persons and presents an assessment of the central hemodynamic parameter depending on the type of autonomic reactivity of the cardiovascular system.Methods. The study involved measuring systolic and diastolic blood pressure, heart rate, and anthropometric measurements for calculating the corresponding indices. An active orthostatic test to determine the functional state of reflex mechanisms for regulating hemodynamics. Statistical methods were used for data analysis.Results. Based on anthropometric indicators and calculated indices, boys and girls with overweight differed from the control group in abdominal and total distribution of fat. However, there were no differences in terms of vegetative tone (sympathicotonic, vagotonic, eutonic). The distribution of eutonic and vagotonic types of the autonomic nervous system and sympathicotonia was similar in both groups. Most overweight individuals had insufficient reactivity of the parasympathetic autonomic nervous system. Paradoxical reactivity in both groups was observed with the same frequency. In the group of people with paradoxical autonomic reactivity among overweight people, a significantly lower increase in heart rate was found than in the control group. In persons with overweight and increased autonomic reactivity, minute blood volume and pulse pressure increased 1.5-fold, there was a tendency to increase stroke volume and inotropic function of the heart. The increase in this characteristic indicated a hyperkinetic type of hemodynamics in overweight persons in the group with normal autonomic reactivity. In groups with paradoxical and increased autonomic reactivity of the cardiovascular system, a normokinetic type of hemodynamics was observed.Conclusions. Signs of altered autonomic reactivity found in most overweight individuals indicate dysfunction of the parasympathetic autonomic nervous system and possible dysfunction of nonspecific regulatory (limbic-reticular) parts of the brain.

The Functional Role of the Renin-Angiotensin System in Preeclampsia

Abstract: The renin-angiotensin system (RAS) is a signaling pathway that acts as a major regulator in human physiology. To sidestep the major intimidations of low blood volume and low blood pressure, the diverse actions of Ang II/ACE/AT1R can be viewed as a useful response in maintaining homeostasis. The deleterious action of the Ang II/ACE/AT1R axis is endogenously counterbalanced by ACE 2/Ang 1-7/MasR. Yet, over activation of the Ang II/ACE/AT1R axis may lead to hypertension. Preeclampsia is characterized by hypertension with proteinuria or end-organ dysfunction after 20 weeks of gestation. The early-onset sort is more genuine and capable of high maternal and fetal dismalness and mortality rates than the late-onset sort of preeclampsia. Various theories for the pathogenesis of preeclampsia are, the exact underlying molecular mechanisms remain unclear but are likely to be multifactorial. Later studies of RAS in preeclampsia have highlighted the need for thorough research on this topic. There is an increase in the levels of circulating angiotensinogen during the first 20 weeks of gestation. At the beginning of the pregnancy, there is an increment of prorenin by 4 - 5 times. Renin synthesis in preeclampsia is suppressed. PE pregnant women have higher levels of prorenin receptor expression in their placental tissue than normal pregnant women. AT1 receptor autoantibodies are also observed. Ang II is raised in normal pregnancies as a result of higher levels of angiotensinogen and renin. Preeclampsia causes a decrease in angiotensin-(1-7) levels. Aldosterone is also relatively low in pregnancies complicated by preeclampsia.

Thirst: neuroendocrine regulation in mammals.

Animals can sense their changing internal needs and then generate specific physiological and behavioural responses in order to restore homeostasis. Water-saline homeostasis derives from balances of water and sodium intake and output (drinking and diuresis, salt appetite and natriuresis), maintaining an appropriate composition and volume of extracellular fluid. Thirst is the sensation which drives to seek and consume water, regulated in the central nervous system by both neural and chemical signals. Water and electrolyte homeostasis depends on finely tuned physiological mechanisms, mainly susceptible to plasma Na+ concentration and osmotic pressure, but also to blood volume and arterial pressure. Increases of osmotic pressure as slight as 1-2% are enough to induce thirst ("homeostatic" or cellular), by activation of specialized osmoreceptors in the circumventricular organs, outside the blood-brain barrier. Presystemic anticipatory signals (by oropharyngeal or gastrointestinal receptors) inhibit thirst when fluids are ingested, or stimulate thirst associated with food intake. Hypovolemia, arterial hypotension, Angiotensin II stimulate thirst ("hypovolemic thirst", "extracellular dehydration"). Hypervolemia, hypertension, Atrial Natriuretic Peptide inhibit thirst. Circadian rhythms of thirst are also detectable, driven by suprachiasmatic nucleus in the hypothalamus. Such homeostasis and other fundamental physiological functions (cardiocircolatory, thermoregulation, food intake) are highly interdependent.

Natriuretic Peptides: It Is Time for Guided Therapeutic Strategies Based on Their Molecular Mechanisms.

Natriuretic peptides (NPs) are the principal expression products of the endocrine function of the heart. They exert several beneficial effects, mostly mediated through guanylate cyclase-A coupled receptors, including natriuresis, diuresis, vasorelaxation, blood volume and blood pressure reduction, and regulation of electrolyte homeostasis. As a result of their biological functions, NPs counterbalance neurohormonal dysregulation in heart failure and other cardiovascular diseases. NPs have been also validated as diagnostic and prognostic biomarkers in cardiovascular diseases such as atrial fibrillation, coronary artery disease, and valvular heart disease, as well as in the presence of left ventricular hypertrophy and severe cardiac remodeling. Serial measurements of their levels may be used to contribute to more accurate risk stratification by identifying patients who are more likely to experience death from cardiovascular causes, heart failure, and cardiac hospitalizations and to guide tailored pharmacological and non-pharmacological strategies with the aim to improve clinical outcomes. On these premises, multiple therapeutic strategies based on the biological properties of NPs have been attempted to develop new targeted cardiovascular therapies. Apart from the introduction of the class of angiotensin receptor/neprilysin inhibitors to the current management of heart failure, novel promising molecules including M-atrial natriuretic peptide (a novel atrial NP-based compound) have been tested for the treatment of human hypertension with promising results. Moreover, different therapeutic strategies based on the molecular mechanisms involved in NP regulation and function are under development for the management of heart failure, hypertension, and other cardiovascular conditions.

Vascular compliance and left ventricular compliance cross talk: Implications for using long-term heat acclimation in cardiac care.

1) The first evidence of the beneficial impact of Long-Term-Heat-Acclimation (LTHA) on cardio-vascular compliance was the positive inotropic response and improved left ventricular (LV) compliance noted when isolated hearts from LTHA rats were studied. Human echo study demonstrates that passive HA affects the right ventricle and the atria as well. 2) There is a cross-talk between vascular and cardiac compliance. Vascular compliance per se is defined by central venous pressure-Blood volume relationship-Global Vascular Compliance (GVC). It is determined by the sum of the vascular compliance of the vessels in every organ in any physiological state, varies with LTHA and thus influences cardiac performance. LTHA improves endothelial function, increases NO (nitric oxide) production, in-turn stimulating alterations in ECM (extracellular matrix) via the TGF β1-SMAD pathway. 3) LTHA is associated with transformation from fast to slow myosin, heat acclimation ischemic/hypoxic cross-tolerance and alterations in the extracellular matrix. 4) A human translational study demonstrated improved LV compliance following bypass surgery in LTHA subjects compared to controls. 5) Diastolic dysfunction and the impact of comorbidities with vascular and non- vascular origins are major contributors to the syndrome of heart failure with preserved ejection function (HFPEF). Unfortunately, there is a paucity of treatment modalities that improve diastolic dysfunction. 6) In the current mini-review we suggest that LTHA may be beneficial to HFPEF patients by remodeling cardiac compliance and vascular response.

PSUN14 Elucidating Effect of Modulating Aldosterone Synthesis on Cell Fate in Human Adrenal Cells

Abstract Introduction Aldosterone regulates sodium homeostasis thereby affecting blood volume and blood pressure. Physiologically, aldosterone is synthesized in the zona glomerulosa (ZG) by aldosterone synthase (CYP11B2) when there is a lack of salt. However, in the adult human adrenal ZG is sparse and confined to discrete islets (1). We hypothesize that the high salt in modern diets change ZG cell function from synthesis to apoptosis/migration mode when aldosterone is not required. This hypothesis is based on: [i] CYP11B2−/− mice, where ZG cells migrate and apoptose (2); [ii] the disappearance from most of human ZG of CYP11B2, which became apparent with selective antisera (3); [iii] apoptosis in monkeys following aldosterone synthase inhibition (4). Herein we aim to test our hypothesis by silencing CYP11B2 in human adrenal cells. Methods The HAC15, a subclone of the H295R human adrenocortical cancer cell line, was transfected with scrambled siRNA (siScrambled) or siRNA targeting CYP11B2 (siCYP11B2) using the Neon™ Transfection System (Thermofisher Scientific, USA). An apoptosis assay 48-h post-transfection was performed using the Pacific Blue™ Annexin V/SYTOX™ AADvanced™ apoptosis kit on the BD FACSVerseTM system (BD Biosciences, USA). The supernatants and cells were harvested for aldosterone and cortisol, and RNA isolation. Experiments were repeated 3 times independently in triplicates. RNA-Sequencing (RNAseq) of siCYP11B2 and siScrambled was performed on a representative sample from each independent experiment (BGI Genomics, China). Results Transfected HAC15 cells with siCYP11B2 showed reduction of aldosterone production by 69.8% (p=0.001) and suppression of CYP11B2 mRNA by 8 folds (p=0.001) compared to control, with no significant change on cortisol production and CYP11B1 mRNA expression. This confirmed that the silencing was specific to CYP11B2 despite the gene being highly homologous to CYP11B1. In all 3 independent experiments, 3 genes were significantly downregulated; CYP11B2, HNRNPA1, and UHMK1 expression in siCYP11B2 cells were 32%, 65% and 67% of matched control siScramble cells. Result of KEGG pathway from each independent experiment showed the most enriched pathways among the differentially expressed genes (DEG) were mitophagy and autophagy. However, analysis of flow cytometric apoptosis assay showed silencing of CYP11B2 did not induce cell apoptosis. Conclusion Our finding showed that silencing of CYP11B2 can affect mitophagy and autophagy but does not affect cell apoptosis in the HAC15 human adrenocortical cancer cell line. Further investigation on cell proliferation and in non-cancerous adrenal cells may be needed to identify the effect of modulating aldosterone synthesis on ZG cell fate. Reference (1) Vinson G., Front Neurosci 2016; 10: 238. (2) Lee G, et al., Endocrinology 2005; 146: 2650–2656. (3) Gomez-Sanchez CE, et al., Mol Cell Endocrinol 2014; 383: 111–117. (4) Bogman K, et al., Hypertension. 2017; 69(1): 189–196. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Photoplethysmography Enabled Wearable Devices and Stress Detection: A Scoping Review.

Mental and physical health are both important for overall health. Mental health includes emotional, psychological, and social well-being; however, it is often difficult to monitor remotely. The objective of this scoping review is to investigate studies that focus on mental health and stress detection and monitoring using PPG-based wearable sensors. A literature review for this scoping review was conducted using the PRISMA (Preferred Reporting Items for the Systematic Reviews and Meta-analyses) framework. A total of 290 studies were found in five medical databases (PubMed, Medline, Embase, CINAHL, and Web of Science). Studies were deemed eligible if non-invasive PPG-based wearables were worn on the wrist or ear to measure vital signs of the heart (heart rate, pulse transit time, pulse waves, blood pressure, and blood volume pressure) and analyzed the data qualitatively. Twenty-three studies met the inclusion criteria, with four real-life studies, eighteen clinical studies, and one joint clinical and real-life study. Out of the twenty-three studies, seventeen were published as journal-based articles, and six were conference papers with full texts. Because most of the articles were concerned with physiological and psychological stress, we decided to only include those that focused on stress. In twelve of the twenty articles, a PPG-based sensor alone was used to monitor stress, while in the remaining eight papers, a PPG sensor was used in combination with other sensors. The growing demand for wearable devices for mental health monitoring is evident. However, there is still a significant amount of research required before wearable devices can be used easily and effectively for such monitoring. Although the results of this review indicate that mental health monitoring and stress detection using PPG is possible, there are still many limitations within the current literature, such as a lack of large and diverse studies and ground-truth methods, that need to be addressed before wearable devices can be globally useful to patients.