Effects of Interrupting Prolonged Sitting with Light-Intensity Physical Activity on Inflammatory and Cardiometabolic Risk Markers in Young Adults with Overweight and Obesity: Secondary Outcome Analyses of the SED-ACT Randomized Controlled Crossover Trial.

Sedentary behavior (SB) is an essential risk factor for obesity, cardiovascular disease, and type 2 diabetes. Though certain levels of physical activity (PA) may attenuate the detrimental effects of SB, the inflammatory and cardiometabolic responses involved are still not fully understood. The focus of this secondary outcome analysis was to describe how light-intensity PA snacks (LIPASs, alternate sitting and standing, walking or standing continuously) compared with uninterrupted prolonged sitting affect inflammatory and cardiometabolic risk markers. Seventeen young adults with overweight and obesity participated in this study (eight females, 23.4 ± 3.3 years, body mass index (BMI) 29.7 ± 3.8 kg/m2, glycated hemoglobin A1C (HbA1c) 5.4 ± 0.3%, body fat 31.8 ± 8.2%). Participants were randomly assigned to the following conditions which were tested during an 8 h simulated workday: uninterrupted prolonged sitting (SIT), alternate sitting and standing (SIT-STAND, 2.5 h total standing time), continuous standing (STAND), and continuous walking (1.6 km/h; WALK). Each condition also included a standardized non-relativized breakfast and lunch. Venous blood samples were obtained in a fasted state at baseline (T0), 1 h after lunch (T1) and 8 h after baseline (T2). Inflammatory and cardiometabolic risk markers included interleukin-6 (IL-6), c-reactive protein (CRP), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), visceral fat area (VFA), triglyceride-glucose (TyG) index, two lipid ratio measures, TG/HDL-C and TC/HDL-C, albumin, amylase (pancreatic), total protein, uric acid, and urea. We found significant changes in a broad range of certain inflammatory and cardiometabolic risk markers during the intervention phase for IL-6 (p = 0.014), TG (p = 0.012), TC (p = 0.017), HDL-C (p = 0.020), LDL-C (p = 0.021), albumin (p = 0.003), total protein (p = 0.021), and uric acid (p = 0.040) in favor of light-intensity walking compared with uninterrupted prolonged sitting, alternate sitting and standing, and continuous standing. We found no significant changes in CRP (p = 0.529), creatinine (p = 0.199), TyG (p = 0.331), and the lipid ratios TG/HDL-C (p = 0.793) and TC/HDL-C (p = 0.221) in response to the PA snack. During a simulated 8 h work environment replacement and interruption of prolonged sitting with light-intensity walking, significant positive effects on certain inflammatory and cardiometabolic risk markers were found in young adults with overweight and obesity.

Effects of light-intensity physical activity on cardiometabolic parameters in young adults with overweight and obesity: The SED-ACT randomized controlled crossover trial.

AIMS: To investigate how a change in body position with light-intensity physical activity (PA) 'snacks' (LIPAS, alternate sitting and standing, walking or standing continuously) compared with uninterrupted prolonged sitting affects glucose metabolism and heart rate variability (HRV) parameters in young adults with overweight and obesity. MATERIALS AND METHODS: We conducted a four-arm randomized controlled crossover trial. The following conditions were tested during an 8-h simulated workday: uninterrupted prolonged sitting (SIT), alternate sitting and standing (SIT-STAND; 2.5 h total), continuous standing (STAND), and continuous walking (1.0 mph; WALK). The primary outcome was to investigate how a change in body position (alternate sitting and standing, walking or standing continuously) compared with uninterrupted sitting affects mean 8-h glucose metabolism. Secondary outcomes included the effects on 2-h postprandial glucose concentrations, as well as on 8-h/24-h heart rate and HRV parameters, in the respective study arms. Capillary blood samples were drawn from an hyperemised earlobe in the fasted state and once every hour during each trial intervention by puncturing the earlobe with a lancet and collecting 20 µL of blood (Biosen S-Line Lab+; EKF diagnostics, Barleben, Germany). HRV was assessed for 24 h including the 8-h intervention phase, and a home phase by means of a Holter electrocardiogram. All participants received the same standardized non-relativised breakfast and lunch during the four trial visits. RESULTS: Seventeen individuals (eight women, mean age 23.4 ± 3.3 years, body mass index 29.7 ± 3.8 kg/m2, glycated haemoglobin level 34.8 ± 3.1 mmol/mol [5.4 ± 0.3%], body fat 31.8 ± 8.2%) completed all four trial arms. Compared with SIT (89.4 ± 6.8 mg/dL), 8-h mean glucose was lower in all other conditions (p < 0.05) and this was statistically significant compared with WALK (86.3 ± 5.2 mg/dL; p = 0.034). Two-hour postprandial glucose after breakfast was approximately 7% lower for WALK compared with SIT (p = 0.002). Furthermore, significant time × condition effects on HRV parameters favouring light-intensity walking were observed (p < 0.001). CONCLUSIONS: Replacement and interruption of prolonged sitting with light-intensity walking showed a significant blood glucose-lowering effect and improved HRV during an 8-h work environment in young adults with overweight and obesity.

Orthostatic Challenge-Induced Coagulation Activation in Young and Older Persons.

The incidence of thrombosis increases with aging. We investigated the coagulatory/haemostatic system across the ages and tested the hypothesis that older persons have a hypercoagulable state compared to younger persons at rest, and that standing up (orthostasis) leads to greater changes in coagulation in older persons. In total, 22 older and 20 young participants performed a 6 min sit-to-stand test (orthostatic challenge). Blood was collected prior to and at the end of standing and haemostatic profiling was performed via thrombelastometry (TEM), calibrated automated thrombogram (CAT) and standard coagulation assays. At baseline, three CAT-derived values indicated enhanced capability to generate thrombin in older participants. However, other measured parameters did not suggest a hypercoagulable state in older participants: prolonged TEM-derived coagulation times (295 vs. 209 s, medians, p = 0.0025) and prothrombin times (103 vs. 114%, medians, p = 0.0087), as well as lower TF levels (440 vs. 672 pg/mL, medians, p = 0.0245) and higher t-PA levels (7.3 vs. 3.8 ng/mL, medians, p = 0.0002), indicative of enhanced fibrinolytic capability, were seen. Younger participants were more sensitive to the orthostatic challenge: CAT-derived endogenous thrombin potentials (ETPs) were only increased in the young (1337 to 1350 nM.min, medians, p = 0.0264) and shortening of PTs was significantly higher in the young vs. older participants (p = 0.0242). Our data suggest that the increased thrombosis propensity in older persons is not primarily attributable to a hyperactive coagulation cascade but may be due to other pathologies associated with aging.

Children's hair cortisol and hair testosterone concentrations in response to environmental changes: from summer holidays to school.

Elevated hair cortisol concentrations in children have been linked to several stress-related conditions, including school-related demands. However, little is known about changes in hair testosterone in children. The present study investigated changes in hair cortisol and hair testosterone concentrations in the time course of four months - from summer holidays until mid of autumn of the following school year - in 60, 10-12-year-old (11.31 ± 0.63) school children (29 girls). Children's mental health was assessed by the strengths and difficulties questionnaire (SDQ) and related to hair cortisol and hair testosterone levels. Body mass index, waist-to-height ratio, and parental education were evaluated as potential confounders. In girls, the expected increase of hair cortisol concentrations was observed during school as compared to summer holidays, partly accounted for by peer- and emotional problems and the increase of HTC. In boys, hair cortisol and testosterone concentrations were significantly higher. Hair cortisol increased only slightly, while hair testosterone decreased significantly during school. The findings suggest a reciprocal influence of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axis, differentially affecting girls' and boys' hormone production in response to environmental changes.

Differences in Hemodynamic, Hormonal and Heart Rate Variability Parameters in Complication-Free Pregnancies Compared to Individuals with Gestational Diabetes Mellitus and Preeclampsia: An Observational Retrospective Analysis.

To investigate differences in hemodynamic, hormonal and heart rate variability parameters in women following complication-free pregnancies (healthy), preeclampsia and gestational diabetes mellitus (GDM) after giving childbirth. Data of 60 women (healthy: n = 29, age 32.7 ± 4.5 years, BMI 24.2 ± 4.3 kg/m2; preeclampsia: n = 16, age 35.3 ± 4.4 years, 28.5 ± 6.4 kg/m2; GDM, n = 15, age 32.3 ± 6.0 years, BMI 26.4 ± 6.2 kg/m2) were included. Two visits were conducted 16 and 48 weeks after giving childbirth. Hair samples were taken for analysis of cortisol and testosterone. ECG and blood pressure were recorded at each visit. Data were analyzed via RM-ANOVA and post-hoc testing (p ≤ 0.05). Heart rate increased from visit 1 to visit 2, whereas SDNN decreased (both p = 0.03). RMSSD showed an increased trend for groups (p = 0.06). Testosterone in the GDM group was significantly higher compared to the other groups (p = 0.002). Cortisol levels were significantly higher following post-hoc testing GDM was different compared to healthy individuals (p = 0.02). Hemodynamic changes from week 16 to week 48 did not differ between groups (p > 0.05). No differences between individuals with preeclampsia and healthy individuals were found for all hemodynamic parameters (p > 0.05). The study showed higher levels of chronic stress indicators in GDM measured via heart rate variability and cortisol compared to women with a history of preeclampsia and healthy women.

Effects of physical therapy on hyaluronan clearance and volume regulating hormones in lower limb lymphedema patients: A pilot study.

Lymphedema is manifested as a chronic swelling arising due to stasis in the lymphatic flow. No cure is currently available. A non-invasive treatment is a 3 week complete decongestive therapy (CDT), including manual lymphatic drainage and compression bandaging to control swelling. As CDT leads to mobilization of several liters of fluid, effects of CDT on hyaluronan clearance (maker for lymphatic outflow), volume regulating hormones, total plasma protein as well as plasma density, osmolality and selected electrolytes were investigated. In this pilot study, we assessed hyaluronan and volume regulating hormone responses from plasma samples of nine patients (three males, six females, aged 55 ± 13 years) with lower limb lymphedema stage II-III, before - and after - CDT. A paired non-parametric test (Wilcoxon) was used to assess hormonal and plasma volume changes. Correlation was tested using Spearman's correlation. The main findings of this novel study are that lymphedema patients lost volume and weight after therapy. Hyaluronic acid did not significantly change pre- compared to post-CDT. Aldosterone increased significantly after therapy, while plasma renin activity increased, but not significantly. Plasma total protein, density, osmolality and sodium and chloride did not show differences after CDT. To our knowledge, no study has previously investigated the effects of CDT on volume regulating hormones or electrolytes. To identify the time-course of volume regulating hormones and lymphatic flow changes induced by CDT, future studies should assess these parameters serially over 3 weeks of therapy.

Lecture recording, microlearning, video conferences and LT-platform - medical education during COVID-19 crisis at the Medical University of Graz.

Objective: In the course of the COVID-19 crisis it became necessary to convert the majority of classroom teaching to e-learning. This should be done in a uniform and transparent way for the study programs of the Medical University of Graz. Methodology: We built on the Virtual Medical Campus, which has existed since 2003. For the summer semester 2020, we focused on an expansion of the automatic lecture recording system, microlearning and the implementation of video conferences as well as the learning platform LT. Results: The number of lecture recordings increased from 170 to more than 700, weekly accesses reached more than 80,000, with nearly 4,200 students. In the Microlearning system, an average of 82,516+-12,071 SEM learning steps per week were completed, which represented a highly significant increase compared to the same period of the previous year (15,101+-4,278 SEM; t-test: t=5,2638, p<0,0001). Video conferencing via WebEx was a newly introduced tool that was used extensively for interactive seminars, but also for oral exams. The LT platform from AdInstruments was successfully used as a replacement for practical training, especially in physiology. Conclusions: Based on sufficient preparatory work, a rapid expansion of e-learning ensured that teaching could be continued in the form of home learning despite the exceptional situation caused by COVID-19. Success factors were the provision of selected technical tools, consistent communication of the university management and technical and content support for teachers and students by a central staff unit.

Phasic heart rate variability and the association with cognitive performance: A cross-sectional study in a healthy population setting.

INTRODUCTION: Sympathovagal balance measured by heart rate variability is a core component of psychophysiological research. Through the close link of physiological and psychological aspects, often a reduced heart rate variability is associated with impaired cognitive function. A better understanding of the associations between cognitive and cardiovascular dysfunctions is necessary to prevent the manifestation of diseases. Therefore, this study investigated phasic heart rate variability using rest, anticipatory, stress, and recovery periods and the association with high and low cognitive performance in a generally healthy population setting. METHODS: 114 healthy individuals (40 males, 74 females) aged 20 to 70 participated in the cross-sectional study. The heart rate variability based on standard deviation of NN intervals (SDNN), and the root means square of successive differences (RMSSD), low frequency (LF), high frequency (HF) and LF/HF ratio and its association with high and low cognitive performance measured by the California Verbal Learning Task II were examined. RESULTS: The results of this study indicate that the paradigm was successful in producing stress and showed a significant association between phasic heart rate variability (SDNN) and verbal episodic memory performance, irrespective of age and sex. DISCUSSION: The results of this study suggest that a reduced heart rate variability is associated with reduced cognitive function regardless of age and sex and seem to be an early indicator of sympathovagal disbalance. CONCLUSION: This leads to the conclusion that differences between high and low cognitive performance might show differences in heart rate variability at an early stage, where no diseases are yet manifest.

Postural hemodynamic parameters in older persons have a seasonal dependency : A pilot study.

AIMS: It is known that blood pressure regulation differs seasonally. It is unknown, however, how the cardiovascular system in patients with a stroke reacts to postural changes in different seasons. The aim was therefore to investigate how different temperatures in cold and warm seasons influence the reactions of haemodynamic mechanisms as well as heart rate variability during a sit-to-stand test in patients with stroke and a control group. METHODS: Hemodynamic responses were assessed in both groups during a sit-to-stand test (5 min sitting followed by 5 min standing) beat to beat within two different seasons. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP), heart rate (HR), stroke index (SI), cardiac index (CI) and heart rate variability (HRV) were continuously monitored. RESULTS: During the sitting baseline period delta values of DBP (+15.1 [Standard error (SE) 3.75] mmHg, p < 0.05) and MBP (+14.35 [SE 4.18] mmHg, p < 0.05) were significantly higher in colder months compared to warmer months whereas SI (-3.86 [SE 1.43] ml/beat/m2, p < 0.05) and CI (-0.4 [SE 0.11] l/min/m2, p < 0.05) were lower in colder months compared to warmer months in non-stroke participants. In patients with stroke during sitting, baseline period delta values of DBP (+19.92 [SE 8.03] mmHg, p < 0.05) and MBP (+19.29 [SE 8.6] mmHg, p < 0.05) were significantly higher in colder months compared to warmer months but SI (-5.43 [SE 1.96] ml/beat/m2, p < 0.05) was significantly lower in colder months compared to warmer months. After standing, there was a significant decrease in SBP in warmer months (-16.84 [SE 4.38] mmHg, p < 0.05) and a decrease in DBP in warmer months (-7.8 [SE 2.3] mmHg, p < 0.05) and colder months (-6.73 [SE 1.5] mmHg, p < 0.05) in non-stroke participants and a decrease in MBP in warmer months (-12.5 [SE 2.8] mmHg, p < 0.05) and colder months (-8.93 [SE 1.8] mmHg, p < 0.05) in non-stroke participants and in warmer months (-14.54 [SE 4.1] mmHg, p < 0.05) in patients with stroke. CONCLUSION: Elderly with and without stroke respond to orthostatic stress with a greater drop in blood pressure in the warmer seasons.

Coagulation changes induced by lower-body negative pressure in men and women.

We investigated whether lower-body negative pressure (LBNP) application leads to coagulation activation in whole blood (WB) samples in healthy men and women. Twenty-four women and 21 men, all healthy young participants, with no histories of thrombotic disorders and not on medications, were included. LBNP was commenced at -10 mmHg and increased by -10 mmHg every 5 min until a maximum of -40 mmHg. Recovery up to 10 min was also monitored. Blood samples were collected at baseline, at end of LBNP, and end of recovery. Hemostatic profiling included comparing the effects of LBNP on coagulation values in both men and women using standard coagulation tests, calibrated automated thrombogram, thrombelastometry, impedance aggregometry, and markers of thrombin formation. LBNP led to coagulation activation determined in both plasma and WB samples. At baseline, women were hypercoagulable compared with men, as evidenced by their shorter "lag times" and higher thrombin peaks and by shorter "coagulation times" and "clot formation times." Moreover, men were more susceptible to LBNP, as reflected in their elevated factor VIII levels and decreased lag times following LBNP. LBNP-induced coagulation activation was not accompanied by endothelial activation. Women appear to be relatively hypercoagulable compared with men, but men are more susceptible to coagulation changes during LBNP. The application of LBNP might be a useful future tool to identify individuals with an elevated risk for thrombosis, in subjects with or without history of thrombosis. NEW & NOTEWORTHY LBNP led to coagulation activation determined in both plasma and whole blood samples. At baseline, women were hypercoagulable compared with men. Men were, however, more susceptible to coagulation changes during LBNP. LBNP-induced coagulation activation was not accompanied by endothelial activation. The application of LBNP might be a useful future tool to identify individuals with an elevated risk for thrombosis, in subjects with or without history of thrombosis.

Adrenomedullin and galanin responses to orthostasis in older persons.

BACKGROUND: Neuroendocrine responses to orthostasis may be critical in the maintenance of mean arterial pressure in healthy individuals. A greater reduction in orthostatic tolerance with age may relate to modulation of hormonal responses such as adrenomedullin and galanin. Thus, we investigated (i) whether adrenomedullin and galanin concentrations increase during orthostatic challenge in older subjects, (ii) whether adrenomedullin and galanin concentrations are higher in older females compared with older males when seated and during orthostatic challenge, and (iii) whether postural changes in plasma concentrations of galanin are correlated with levels of adrenomedullin in either older females or males. MATERIALS AND METHODS: Subjects (n = 18; 12 ♀; 55-80 years old) performed a sit-to-stand test in a 25°C sensory-minimised environment, with blood samples collected after 4 min of being seated and then when standing. Plasma adrenomedullin and galanin concentrations were determined. RESULTS: Baseline plasma concentration of adrenomedullin (5·35 ± 0·74 (n = 12, females) vs. 7·40 ± 1·06 pg/mL (n = 5, males)) and galanin (64·07 ± 9·05 vs. 98·99 ± 16·90 pg/mL, respectively) did not significantly differ between genders. Furthermore, plasma adrenomedullin and galanin concentrations were not significantly affected by adoption of the upright posture in either gender and were not correlated in females or males. CONCLUSIONS: Adrenomedullin and galanin concentrations were similar between genders and did not change following adoption of the standing posture. To further clarify the roles, these hormones play in orthostatic intolerance, adrenomedullin and galanin concentrations should be assessed in participants who show presyncopal symptoms during an orthostatic challenge.

Stress-Related Changes in Body Form: Results from the Whitehall II Study.

OBJECTIVE: Stress is associated with body mass gain in some people but with body mass loss in others. When the stressor persists, some people adapt with their stress responses, whereas others do not. Heart rate variability (HRV) reflects autonomic variability and is related to stress responses to psychosocial challenges. It was hypothesized that the combined effects of stress exposure and autonomic variability predict long-term changes in body form. METHODS: Data of 1,369 men and 612 women from the Whitehall II cohort were analyzed. BMI, hip-to-height ratio, and waist-to-height ratio were measured at three time points over a 10-year period. HRV and psychological distress (General Health Questionnaire) were assessed. RESULTS: Men with high psychological distress were at risk of developing an increased waist-to-height ratio (F = 3.4, P = 0.038). Men with high psychological distress and low HRV were prone to develop an increased body mass and hip-to-height ratio (psychological distress: F = 4.3, P = 0.016; HRV: F = 5.0, P = 0.008). Statistical trends showed that women displayed similar patterns of stress-related changes in body form (P = 0.061; P = 0.063). CONCLUSIONS: Assessing psychological distress and autonomic variability predicts changes in body form. Psychological distress was found to be associated with an increased risk of developing the wide-waisted phenotype, while psychological distress combined with low autonomic variability was associated with an increased risk of developing the corpulent phenotype.

Poststroke alterations in heart rate variability during orthostatic challenge.

Older adults following recovery from ischemic stroke have a higher incidence of orthostatic hypotension, syncope, and fall risk, which may be related to impaired autonomic responses limiting the ability to maintain cerebral blood flow. Thus, we investigated cerebrovascular and cardiovascular regulation in 23 adults ≥55 years of age, 10 diagnosed with ischemic stroke, and 13 age-matched healthy controls when sitting at rest and upon standing to compare differences of autonomic variables at ∼7 months (218 ±â€Š41 days) poststroke.Arterial blood pressure via finger plethysmography, muscle-pump baroreflex via electromyography, heart rate variability via 3-lead ECG, and cerebral blood flow velocity via transcranial Doppler were analyzed while sitting for 5 minutes and then during quiet standing for 5 minutes.From the seated to standing position, the stroke group had significantly greater decline in the low frequency component of heart rate variability (164 [79] vs 25 [162] ms; P = 0.043). All other cardiovascular parameters and assessments of autonomic function were not significantly different between the two groups.Our findings support the hypothesis of continued autonomic dysfunction after recovery from ischemic stroke, with potential attenuation of the cardiovascular response to standing. However, further investigation is required to determine the mechanisms underlying the increased risk of orthostatic hypotension, syncope, and falls poststroke.

Orthostatic Challenge Shifts the Hemostatic System of Patients Recovered from Stroke toward Hypercoagulability.

Aims: The objective of our study was to assess the effects of orthostatic challenge on the coagulation system in patients with a history of thromboembolic events and to assess how they compared with age-matched healthy controls. Methods: Twenty-two patients with histories of ischemic stroke and 22 healthy age-matched controls performed a sit-to-stand test. Blood was collected prior to- and at the end of- standing in the upright position for 6 min. Hemostatic profiling was performed by determining thrombelastometry and calibrated automated thrombogram values, indices of thrombin generation, standard coagulation times, markers of endothelial activation, plasma levels of coagulation factors and copeptin, and hematocrit. Results: Orthostatic challenge caused a significant endothelial and coagulation activation in patients (Group 1) and healthy controls (Group 2): Plasma levels of prothrombin fragment F1+2 were increased by approximately 35% and thrombin/antithrombin-complex (TAT) increased 5-fold. Several coagulation variables were significantly altered in Group 1 but not in Group 2: Coagulation times (CTs) were significantly shortened and alpha angles, peak rate of thrombin generation (VELINDEX), tissue factor (TF) and copeptin plasma levels were significantly increased (comparison between standing and baseline). Moreover, the shortening of CTs and the rise of copeptin plasma levels were significantly higher in Group 1 vs. Group 2 (comparison between groups). Conclusion: The coagulation system of patients with a history of ischemic stroke can be more easily shifted toward a hypercoagulable state than that of healthy controls. Attentive and long-term anticoagulant treatment is essential to keep patients from recurrence of vascular events.

Effect of postural changes on cardiovascular parameters across gender.

INTRODUCTION: We investigated the effect of postural changes on various cardiovascular parameters across gender. Twenty-eight healthy subjects (16 male, 12 female) were observed at rest (supine) and subjected to 3 interventions; head-down tilt (HDT), HDT with lower body negative pressure (HDT+ LBNP at -30 mm Hg), and head-up tilt (HUT), each for 10 minutes separated by a 10 minutes recovery period. METHODS: Measurements were recorded for heart rate (HR), standard deviation of the normal-to-normal intervals, root mean square of successive differences between the normal-to-normal intervals, heart rate variability-low frequency (LFRRI), heart rate variability-high frequency (HFRRI), low frequency/high frequency ratio (LFRRI/HFRRI), systolic blood pressure (SBP), mean arterial pressure (MAP), diastolic blood pressure (DBP), total peripheral resistance index (TPRI), stroke index (SI), cardiac index (CI), index of contractility (IC), left ventricular work index, and left ventricular ejection time. RESULTS: Across all cardiovascular parameters, there was a significant main effect of the intervention applied but there was no significant main effect of gender across all parameters. CONCLUSIONS: The results suggest that there are no specific gender differences in regards to the measured variables under the conditions of this study. Furthermore, these results suggest that in healthy subjects, there appears to be evidence that LBNP partially elicits similar cardiovascular responses to HUT, which supports the use of LBNP as an intervention to counteract the effects of central hypovolemia.

Effects of individualized centrifugation training on orthostatic tolerance in men and women.

AIMS: Exposure to artificial gravity (AG) at different G loads and durations on human centrifuges has been shown to improve orthostatic tolerance in men. However, the effects on women and of an individual-specific AG training protocol on tolerance are not known. METHODS: We examined the effects of 90 minutes of AG vs. 90 minutes of supine rest on the orthostatic tolerance limit (OTL), using head up tilt and lower body negative pressure until presyncope of 7 men and 5 women. Subjects were placed in the centrifuge nacelle while instrumented and after one-hour they underwent either: 1) AG exposure (90 minutes) in supine position [protocol 1, artificial gravity exposure], or 2) lay supine on the centrifuge for 90 minutes in supine position without AG exposure [protocol 2, control]. The AG training protocol was individualized, by first determining each subject's maximum tolerable G load, and then exposing them to 45 minutes of ramp training at sub-presyncopal levels. RESULTS: Both sexes had improved OTL (14 minutes vs 11 minutes, p < 0.0019) following AG exposure. When cardiovascular (CV) variables at presyncope in the control test were compared with the CV variables at the same tilt-test time (isotime) during post-centrifuge, higher blood pressure, stroke volume and cardiac output and similar heart rates and peripheral resistance were found post-centrifuge. CONCLUSIONS: These data suggest a better-maintained central circulating blood volume post-centrifugation across gender and provide an integrated insight into mechanisms of blood pressure regulation and the possible implementation of in-flight AG countermeasure profiles during spaceflights.

Influence of bed rest on plasma galanin and adrenomedullin at presyncope.

BACKGROUND: The role of hormones in reduced orthostatic tolerance following long-term immobilization remains uncertain. We have previously shown that plasma concentrations of adrenomedullin and galanin, two peptides with vasodepressor properties, rise significantly during orthostatic challenge. We tested the hypothesis that bedrest immobilization increases the rise in adrenomedullin and galanin during orthostatic challenge leading to presyncope. MATERIALS AND METHODS: We measured baseline (supine), presyncope and recovery (10 min postpresyncope, supine) levels of adrenomedullin and galanin in 8 healthy men, before and after 21 days of -6° head-down bed rest (HDBR). Presyncope was elicited using a combined head-up tilt and graded lower body negative pressure protocol. Orthostatic tolerance was defined as the time taken from the commencement of head-up tilt to the development of presyncope. RESULTS: Orthostatic tolerance time after HDBR reduced by 8·36 ± 5·39 min (P = 0·0032). HDBR increased plasma adrenomedullin concentration to orthostatic challenge (P = 0·0367). Compared to pre-HDBR, a significant rise in post-HDBR presyncopal (P < 0·001) and recovery adrenomedullin concentration (P < 0·01) was demonstrated. In contrast, we observed no change in pre- and post-HDBR galanin levels to orthostatic challenge. CONCLUSIONS: Bedrest immobilization appears to affect adrenomedullin levels in that greater increases in adrenomedullin occur at presyncope following bedrest immobilization. Due to its peripheral vasculature hypotensive effect, the greater levels of adrenomedullin at presyncope following bedrest immobilization may have contributed to the reduced orthostatic capacity postbedrest.

Effect of computerized cognitive training with virtual spatial navigation task during bed rest immobilization and recovery on vascular function: a pilot study.

We investigated the effects of bed rest (BR) immobilization, with and without computerized cognitive training with virtual spatial navigation task (CCT), on vascular endothelium on older subjects. The effects of 14-day BR immobilization in healthy older males (n=16) of ages 53-65 years on endothelial function were studied using EndoPAT(®), a noninvasive and user-independent method. From the group of 16 older men, 8 randomly received CCT during the BR, using virtual navigation tasks in a virtual environment with joystick device. In all the cases, EndoPAT assessments were done at pre- and post-BR immobilization as well as following 28 days of ambulatory recovery. The EndoPAT index increased from 1.53±0.09 (mean ± standard error of the mean) at baseline to 1.61±0.16 following immobilization (P=0.62) in the group with CCT. The EndoPAT index decreased from 2.06±0.13 (mean ± standard error of the mean) at baseline to 1.70±0.09 at the last day of BR study, day 14 (BR14) (P=0.09) in the control group. Additionally, there were no statistically significant differences between BR14 and at 28 days of follow-up (rehabilitation program) (R28). Our results show a trend of immobilization in older persons affecting the vasoconstrictory endothelial response. As the control subjects had a greater increase in EndoPAT index after R28 (+0.018) compared to subjects who had cognitive training (+0.11) (calculated from the first day of BR study), it is possible that cognitive training during BR does not improve endothelial function but rather contributes to slowing down the impairment of endothelial function. Finally, our results also show that EndoPAT may be a useful noninvasive tool to assess the vascular reactivity.

Modeling of hyaluronan clearance with application to estimation of lymph flow.

One of the important factors in blood pressure regulation is the maintenance of the level of blood volume, which depends on several factors including the rate of lymph flow. Lymph flow can be measured directly using cannulation of lymphatic vessels, which is not clinically feasible, or indirectly by the tracer appearance rate, which is the rate at which macromolecules appear into the blood from the peritoneal cavity. However, indirect lymph flow measurements do not always provide consistent results. Through its contribution to osmotic pressure and resistance to flow, the macromolecule hyaluronan takes part in the regulation of tissue hydration and the maintenance of water and protein homeostasis. It arrives in blood plasma through lymph flow. Lymphatic hyaluronic acid (HA, hyaluronan) concentration is several times higher than that in plasma, suggesting that the lymphatic route may account for the majority of HA found in plasma. Furthermore, circulating levels of HA reflect the dynamic state between delivery to-and removal from-the bloodstream. To develop an accurate estimation of the fluid volume distribution and dynamics, the rate of lymph flow needs to be taken into account and hyaluronan could be used as a marker in estimating this flow. To examine the HA distribution and system fluid dynamics, a six-compartment model, which could reflect both the steady-state relationships and qualitative characteristics of the dynamics, was developed. This was then applied to estimate fluid shifts from the interstitial space via the lymphatic system to the plasma during different physiological stresses (orthostatic stress and the stress of ultrafiltration during dialysis). Sensitivity analysis shows that during ultrafiltration, lymph flow is a key parameter influencing the total HA level, thus suggesting that the model may find applications in addressing the problem of estimating lymph flow. Since the fluid balance between interstitium and plasma is maintained by lymph flow and microvasculature filtration, our novel method of flow estimation may provide an important tool for understanding fluid dynamics during perturbations of the cardiovascular system. Since the fluid balance between interstitium and plasma is maintained by lymph flow and microvasculature filtration, our novel method of flow estimation may provide an important tool for understanding fluid dynamics during perturbations of the cardiovascular system.

Hormonal and plasma volume changes after presyncope.

BACKGROUND: Aim of this study was to test the hypothesis that after presyncope, some blood hormone pools increase while others decrease. MATERIALS AND METHODS: In twelve healthy male adults, we determined plasma volume changes with plasma mass densitometry and hormone levels. The following were compared: supine rest, presyncope and 20-min post-presyncopal supine rest. We determined plasma renin activity (PRA), aldosterone, adrenocorticotropic hormone (ACTH), adrenomedullin and vasopressin (AVP) from venous blood samples. RESULTS: Using passive 4-min 70° head-up tilt followed by 4-min sequences of additional lower body negative pressure of increasing intensity (15 mmHg steps), presyncope occurred after 11·6 ± 2·8 min, at which time plasma volume was reduced by 15·5 ± 7·4%, aldosterone increased by 37%, ACTH by 75%, PRA by 187% and AVP about 16-fold in average (all P < 0·01); no significant changes in adrenomedullin were seen. Twenty-min post-presyncope, ACTH increased above presyncopal levels (+36%, P < 0·05), aldosterone by 35% (P = 0·07). PRA (-47%, P < 0·01) and AVP (-84%, P < 0·05) decreased below presyncopal but were still above supine control (P < 0·01); similarly, plasma density fell by 2·17 ± 0·97 g L(-1) below presyncopal (P < 0·01), but above supine control (P < 0·05), indicating rapid recovery (83% of initial plasma volume). CONCLUSIONS: We conclude that during the 20-min supine post-syncopal period, plasma volume, PRA and AVP return closer to baseline but aldosterone and ACTH continue increasing. The magnitude of observed concentration changes cannot be explained by haemoconcentration/haemodilution, rather it appears that the observed changes are indicative of hormone-specific endocrine activation patterns in the recovery phase.