Vascular and vegetative factors of glaucoma attack

Purpose. To study the involvement of vascular and vegetative factors in the pathogenesis of glaucoma attack. Material and methods. 12 patients (24 eyes) aged 49 to 82 — 5 men and 7 women, including 3 patients with acute glaucoma and 9 patients with subacute glaucoma were subjected to an ophthalmological examination that included visometry, tonometry, automated static perimetry, OCT and OCT angiography. They were also tested for heart rate variability (HRV) using a Polar heart rate monitor, and for plasminogen content and products of fibrin/fibrinogen degradation in the tear. For comparison, the contralateral eyes of these patients were examined. Results. In the eyes with an acute glaucoma attack, the vascular network was noticeably weakened, especially in the area of the deep peripapillary vascular plexus at the lamina cribrosa level, and focal capillary loss was observed. The peripapillary density of the deep vascular plexus in the eyes with an acute attack was 33.0 ± 5.6 % (М ± m), which was significantly (p < 0.01) lower as compared to 50.0 ± 4.7 % in the unaffected eyes. This indicator correlated with the thickness of the ganglion cell complex (GCC) (p < 0.01). In unaffected eyes, no correlations were found between these glaucoma-related parameters. A significant amount of fibrin/fibrinogen degradation products was found in the tear of glaucoma patients, which may point to a violation of blood circulation in the optic nerve vessels. It has been established that glaucoma attack occurs with increased activity of sympathetic regulation of blood flow. Conclusion. When monitoring this contingent of patients, it is essential to determine the sympathetic-parasympathetic status of the patient. Taking into account the vascular component of the condition, it is expedient to introduce the necessary additions into its treatment plans

REGIONAL ECOLOGICALLY DEPENDENT FEATURES OF THE VEGETATIVE STATUS OF THE POPULATION IN LVIV REGION

In recent years, negative demographic phenomena are growing in Lviv region as well as in Ukraine on the whole. They are manifested in falling birth rates, rising mortality, rising morbidity which are inextricably linked with ecological imbalance and environmental degradation in general. The aim of our research was to identify the features of the degree of stress of the adaptation mechanisms, vegetative status and functional health (of population) of “radiation-clean” Lviv region and compare the results with the results of FEE of “radiation-contaminated” Vinnytsia and Chernihiv regions. We examined 1592 children of different ages and sexes living in Lviv region with the help of functional-vegetative diagnostics (FVD) of vegetative health by the method of V.G. Makats, which allows us to identify indicators of variance of vegetative levels that act as integral bioindicators of internal homeostasis. The bioelectrical activity of 12 symmetrical pairs of functionally active zones of the skin (24 PHASES), 12 on arms and 12 on legs, which reflect the functional activity of the sympathetic and parasympathetic nervous systems was studied. Atmospheric air pollution, drinking water quality, waste accumulation are the main factors that harm the health of the population. Emissions of pollutants into the atmosphere from stationary sources of pollution in Lviv region in 2019 were 16.7% less than in 2018. The overall dynamics of pollutant emissions in 2000-2019 was characterized by a downward trend, from 108.6 thousand tons in 2000 to 88.9 thousand tons in 2019. In 2019, 1.0% more waste was generated in Lviv region than in 2018. In 2019, 858 kg of waste was generated per capita in Lviv region, that is 99 tons per 1 km2. The Lviv region is not included in the radiation control zone of Ukraine and is considered to be «conditionally clean». While studying the variance of vegetative levels and, accordingly, the functional health of children in Lviv region in 2001-2006, we found that in female and male groups vegetative dynamics had a «sympathetic orientation» (critical functional stress of adaptation), so the percentage of surveyed children included in the zone of increase of sympathetic activity fluctuated from 36% in 2006 to 64% in 2004 in the female group under supervision and from 36,5% in 2003 to 55,7% in 2006 in male that is much higher than 15%. of the norms. The critical advantage of «sympathetic dispersion» is not ideal for functional health, but in this situation it indicates the absence of a «radiation component» of the integrated environmental pressure. Functional and ecological examination of Lviv region in 2001-2006 revealed its relation to the zone of «functional protection tension». We noted an opposite situation during long-term observations of the dynamics of functional health of children in Vinnytsia and Chernihiv regions which belong to the 4th zone of state radiation control. In addition, the children living in these regions were characterized by the development of persistent parasympathicotonia (vagotonia). While analyzing the state of functional health of children due to the vegetative coefficient (kV), which characterizes the adaptive potential of the population, it was found that at a rate of kV 0.95-1.05, which corresponds to the vegetative balance, in all gender groups and in all years of observation it is at much higher levels. Its average value ranged from 1.15 in 2002 to 1.30 in 2004 and 1.19 was the overall average for all years of observation. Speaking about children living in Lviv region, there are changes that reflect the imbalance of the autonomic nervous system towards the predominance of sympathetic regulation, accompanied by increased energy needs.Prolonged predominance of sympathetic regulation leads to depletion of energy reserves and, as a consequence, can provoke the emergence and development of diseases of various etiologies.

Investigation of the Sympathetic Regulation in Delayed Onset Muscle Soreness: Results of an RCT

Sports-related pain and injury is directly linked to tissue inflammation, thus involving the autonomic nervous system (ANS). In the present experimental study, we disable the sympathetic part of the ANS by applying a stellate ganglion block (SGB) in an experimental model of delayed onset muscle soreness (DOMS) of the biceps muscle. We included 45 healthy participants (female 11, male 34, age 24.16 ± 6.67 years [range 18–53], BMI 23.22 ± 2.09 kg/m2) who were equally randomized to receive either (i) an SGB prior to exercise-induced DOMS (preventive), (ii) sham intervention in addition to DOMS (control/sham), or (iii) SGB after the induction of DOMS (rehabilitative). The aim of the study was to determine whether and to what extent sympathetically maintained pain (SMP) is involved in DOMS processing. Focusing on the muscular area with the greatest eccentric load (biceps distal fifth), a significant time × group interaction on the pressure pain threshold was observed between preventive SGB and sham (p = 0.034). There was a significant effect on pain at motion (p = 0.048), with post hoc statistical difference at 48 h (preventive SGB Δ1.09 ± 0.82 cm VAS vs. sham Δ2.05 ± 1.51 cm VAS; p = 0.04). DOMS mediated an increase in venous cfDNA -as a potential molecular/inflammatory marker of DOMS- within the first 24 h after eccentric exercise (time effect p = 0.018), with a peak at 20 and 60 min. After 60 min, cfDNA levels were significantly decreased comparing preventive SGB to sham (unpaired t-test p = 0.008). At both times, 20 and 60 min, cfDNA significantly correlated with observed changes in PPT. The 20-min increase was more sensitive, as it tended toward significance at 48 h (r = 0.44; p = 0.1) and predicted the early decrease of PPT following preventive stellate blocks at 24 h (r = 0.53; p = 0.04). Our study reveals the broad impact of the ANS on DOMS and exercise-induced pain. For the first time, we have obtained insights into the sympathetic regulation of pain and inflammation following exercise overload. As this study is of a translational pilot character, further research is encouraged to confirm and specify our observations.

Developmental exposure to DDT or DDE alters sympathetic innervation of brown adipose in adult female mice

Background Exposure to the bioaccumulative pesticide dichlorodiphenyltrichloroethane (DDT) and its metabolite dichlorodiphenyldichloroethylene (DDE) has been associated with increased risk of insulin resistance and obesity in humans and experimental animals. These effects appear to be mediated by reduced brown adipose tissue (BAT) thermogenesis, which is regulated by the sympathetic nervous system. Although the neurotoxicity of DDT is well-established, whether DDT alters sympathetic innervation of BAT is unknown. We hypothesized that perinatal exposure to DDT or DDE promotes thermogenic dysfunction by interfering with sympathetic regulation of BAT thermogenesis. Methods Pregnant C57BL/6 J mice were administered environmentally relevant concentrations of DDTs (p,p’-DDT and o,p’-DDT) or DDE (p,p’-DDE), 1.7 mg/kg and 1.31 mg/kg, respectively, from gestational day 11.5 to postnatal day 5 by oral gavage, and longitudinal body temperature was recorded in male and female offspring. At 4 months of age, metabolic parameters were measured in female offspring via indirect calorimetry with or without the β3 adrenergic receptor agonist, CL 316,243. Immunohistochemical and neurochemical analyses of sympathetic neurons innervating BAT were evaluated. Results We observed persistent thermogenic impairment in adult female, but not male, mice perinatally exposed to DDTs or p,p’-DDE. Perinatal DDTs exposure significantly impaired metabolism in adult female mice, an effect rescued by treatment with CL 316,243 immediately prior to calorimetry experiments. Neither DDTs nor p,p’-DDE significantly altered BAT morphology or the concentrations of norepinephrine and its metabolite DHPG in the BAT of DDTs-exposed mice. However, quantitative immunohistochemistry revealed a 20% decrease in sympathetic axons innervating BAT in adult female mice perinatally exposed to DDTs, but not p,p’-DDE, and 48 and 43% fewer synapses in stellate ganglia of mice exposed to either DDTs or p,p’-DDE, respectively, compared to control. Conclusions These data demonstrate that perinatal exposure to DDTs or p,p’-DDE impairs thermogenesis by interfering with patterns of connectivity in sympathetic circuits that regulate BAT. Graphical abstract

An open-source program to analyze spontaneous sympathetic neurohemodynamic transduction

The pressor responses to spontaneous bursts of muscle sympathetic nerve activity provide important information regarding sympathetic regulation of the circulation. Many laboratories worldwide quantify sympathetic neurohemodynamic transduction using in-house, customized software requiring high-level programming skills and/or costly computer programs. To overcome these barriers, this study presents a simple, open-source, Microsoft Excel-based analysis program along with video instructions to assist researchers without the necessary resources to quantify sympathetic neurohemodynamic transduction.

Torsadogenic Action of Cisapride, dl-Sotalol, Bepridil, and Verapamil Analyzed by the Chronic Atrioventricular Block Cynomolgus Monkeys: Comparison With That Reported in the CiPA In Silico Mechanistic Model

In order to bridge the gap of information between the in silico model and human subjects, we evaluated torsadogenic risk of cisapride, dl-sotalol, bepridil and verapamil selected from 12 training compounds in the comprehensive in vitro proarrhythmia assay using the chronic atrioventricular block monkeys. Cisapride (0, 1, and 5 mg/kg, n = 5 for each dose), dl-sotalol (0, 1, 3, and 10 mg/kg, n = 5 for each dose), bepridil (0, 10, and 100 mg/kg, n = 4 for each dose), verapamil (0, 1.5, 15, and 75 mg/kg, n = 4 for each dose) were orally administered to the monkeys in conscious state. Five mg/kg of cisapride, 1, 3, and 10 mg/kg of dl-sotalol and 100 mg/kg of bepridil prolonged ΔΔQTcF, which was not observed by verapamil. Torsade de pointes was induced by 5 mg/kg of cisapride in 2 out of 5 animals, by 10 mg/kg of dl-sotalol in 5 out of 5 and by 100 mg/kg of bepridil in 2 out of 4, which was not induced by verapamil. These torsadogenic doses were normalized by their maximum clinical daily ones to estimate torsadogenic risk. The order of risk was dl-sotalol &gt;bepridil ≥cisapride &gt;verapamil in our study. Since the order was bepridil ≥dl-sotalol &gt;cisapride &gt;verapamil in comprehensive in vitro proarrhythmia assay (CiPA) in silico mechanistic model validation, sympathetic regulation on the heart may play a pivotal role in the onset of torsade de pointes in vivo.

Abstract 17115: Age-Related Outcomes for Takotsubo Syndrome Differ by Sex

Background: Takotsubo syndrome (TTS) is an uncommon but increasingly recognized cause of myocardial infarction in both women and men across the age spectrum. Emerging data suggest that outcomes are worse in younger compared to older adults, and the extent to which this trend differs by sex is unclear. Methods: Using the National Inpatient Sample data from years 2006 to 2014, we identified hospitalizations with either a primary or secondary diagnosis of TTS. We analyzed these data stratified by age and sex. Outcomes measured include in-hospital mortality and in-hospital complications of cardiac arrest, cardiogenic shock, any type of shock, vasopressor use, intra-aortic balloon pump use, and mechanical ventilation. Results: We identified a total of N=18,051 TTS cases over the study period, most of which were experienced by women (89%). Despite the majority cases occurring in patients over age 50 years (89%), younger patients hospitalized with TTS were consistently more likely to suffer almost all major types of in-hospital complications except for in-hospital mortality ( Figure ). These apparently paradoxical age-based trends were observed in women more so than in men. Conclusion: Our results demonstrate that while individuals age 50 years and older continue to be more frequently hospitalized with TTS than younger patients, younger patients present with greater complications. This age-based finding is seen predominantly in women and much less so in men, potentially related to sex differences in sympathetic regulation of cardiovascular responses to stress. Further research is needed to validate and investigate the potential mechanisms underlying our findings.