Pain associated with intravascular instrumentation reduces orthostatic tolerance and predisposes to vasovagal reactions in healthy young adults without needle phobia: a randomised controlled study.

PURPOSE: Vasovagal syncope (VVS), or fainting, is frequently triggered by pain, fear, or emotional distress, especially with blood-injection-injury stimuli. We aimed to examine the impact of intravenous (IV) instrumentation on orthostatic tolerance (OT; fainting susceptibility) in healthy young adults. We hypothesized that pain associated with IV procedures would reduce OT. METHODS: In this randomised, double-blind, placebo-controlled, cross-over study, participants (N = 23; 14 women; age 24.2 ± 4.4 years) underwent head-up tilt with combined lower body negative pressure to presyncope on three separate days: (1) IV cannulation with local anaesthetic cream (EMLA) (IV + EMLA); (2) IV cannulation with placebo cream (IV + Placebo); (3) sham IV cannulation with local anaesthetic cream (Sham + EMLA). Participants rated pain associated with IV procedures on a 1-5 scale. Cardiovascular (finger plethysmography and electrocardiogram; Finometer Pro), and forearm vascular resistance (FVR; brachial Doppler) responses were recorded continuously and non-invasively. RESULTS: Compared to Sham + EMLA (27.8 ± 2.4 min), OT was reduced in IV + Placebo (23.0 ± 2.8 min; p = 0.026), but not in IV + EMLA (26.2 ± 2.2 min; p = 0.185). Pain was increased in IV + Placebo (2.8 ± 0.2) compared to IV + EMLA (2.0 ± 2.2; p = 0.002) and Sham + EMLA (1.1 ± 0.1; p < 0.001). Orthostatic heart rate responses were lower in IV + Placebo (84.4 ± 3.1 bpm) than IV + EMLA (87.3 ± 3.1 bpm; p = 0.007) and Sham + EMLA (87.7 ± 3.1 bpm; p = 0.001). Maximal FVR responses were reduced in IV + Placebo (+ 140.7 ± 19.0%) compared to IV + EMLA (+ 221.2 ± 25.9%; p < 0.001) and Sham + EMLA (+ 190.6 ± 17.0%; p = 0.017). CONCLUSIONS: Pain plays a key role in predisposing to VVS following venipuncture, and our data suggest this effect is mediated through reduced capacity to achieve maximal sympathetic activation during orthostatic stress. Topical anaesthetics, such as EMLA, may reduce the frequency and severity of VVS during procedures requiring needles and intravascular instrumentation.

Effects of daily artificial gravity training on orthostatic tolerance following 60-day strict head-down tilt bedrest.

PURPOSE: Orthostatic intolerance commonly occurs following immobilization or space flight. We hypothesized that daily artificial gravity training through short-arm centrifugation could help to maintain orthostatic tolerance following head-down tilt bedrest, which is an established terrestrial model for weightlessness. METHODS: We studied 24 healthy persons (eight women; age 33.3 ± 9.0 years; BMI 24.3 ± 2.1 kg/m2) who participated in the 60-days head-down tilt bedrest (AGBRESA) study. They were assigned to 30 min/day continuous or 6 × 5 min intermittent short-arm centrifugation with 1Gz at the center of mass or a control group. We performed head-up tilt testing with incremental lower-body negative pressure until presyncope before and after bedrest. We recorded an electrocardiogram, beat-to-beat finger blood pressure, and brachial blood pressure and obtained blood samples from an antecubital venous catheter. Orthostatic tolerance was defined as time to presyncope. We related changes in orthostatic tolerance to changes in plasma volume determined by carbon dioxide rebreathing. RESULTS: Compared with baseline measurements, supine and upright heart rate increased in all three groups following head-down tilt bedrest. Compared with baseline measurements, time to presyncope decreased by 323 ± 235 s with continuous centrifugation, by 296 ± 508 s with intermittent centrifugation, and by 801 ± 354 s in the control group (p = 0.0249 between interventions). The change in orthostatic tolerance was not correlated with changes in plasma volume. CONCLUSIONS: Daily artificial gravity training on a short-arm centrifuge attenuated the reduction in orthostatic tolerance after 60 days of head-down tilt bedrest.

Running vs. resistance exercise to counteract deconditioning induced by 90-day head-down bedrest.

Spaceflight is associated with enhanced inactivity, resulting in muscular and cardiovascular deconditioning. Although physical exercise is commonly used as a countermeasure, separate applications of running and resistive exercise modalities have never been directly compared during long-term bedrest. This study aimed to compare the effectiveness of two exercise countermeasure programs, running and resistance training, applied separately, for counteracting cardiovascular deconditioning induced by 90-day head-down bedrest (HDBR). Maximal oxygen uptake ( V ˙ O2max), orthostatic tolerance, continuous ECG and blood pressure (BP), body composition, and leg circumferences were measured in the control group (CON: n = 8), running exercise group (RUN: n = 7), and resistive exercise group (RES: n = 7). After HDBR, the decrease in V ˙ O2max was prevented by RUN countermeasure and limited by RES countermeasure (-26% in CON p < 0.05, -15% in RES p < 0.05, and -4% in RUN ns). Subjects demonstrated surprisingly modest orthostatic tolerance decrease for different groups, including controls. Lean mass loss was limited by RES and RUN protocols (-10% in CON vs. -5% to 6% in RES and RUN). Both countermeasures prevented the loss in thigh circumference (-7% in CON p < 0.05, -2% in RES ns, and -0.6% in RUN ns) and limited loss in calf circumference (-10% in CON vs. -7% in RES vs. -5% in RUN). Day-night variations in systolic BP were preserved during HDBR. Decrease in V ˙ O2max positively correlated with decrease in thigh (r = 0.54 and p = 0.009) and calf (r = 0.52 and p = 0.012) circumferences. During this 90-day strict HDBR, running exercise successfully preserved V ˙ O2max, and resistance exercise limited its decline. Both countermeasures limited loss in global lean mass and leg circumferences. The V ˙ O2max reduction seems to be conditioned more by muscular than by cardiovascular parameters.

The effect of water temperature on orthostatic tolerance: a randomised crossover trial.

PURPOSE: Bolus water drinking, at room temperature, has been shown to improve orthostatic tolerance (OT), probably via sympathetic activation; however, it is not clear whether the temperature of the water bolus modifies the effect on OT or the cardiovascular responses to orthostatic stress. The aim of this study was to assess whether differing water temperature of the water bolus would alter time to presyncope and/or cardiovascular parameters during incremental orthostatic stress. METHODS: Fourteen participants underwent three head-up tilt (HUT) tests with graded lower body negative pressure (LBNP) continued until presyncope. Fifteen minutes prior to each HUT, participants drank a 500 mL bolus of water which was randomised, in single-blind crossover fashion, to either room temperature water (20 °C) (ROOM), ice-cold water (0-3 °C) (COLD) or warm water (45 °C) (WARM). Cardiovascular parameters were monitored continuously. RESULTS: There was no significant difference in OT in the COLD (33 ± 3 min; p = 0.3321) and WARM (32 ± 3 min; p = 0.6764) conditions in comparison to the ROOM condition (31 ± 3 min). During the HUT tests, heart rate and cardiac output were significantly reduced (p < 0.0073), with significantly increased systolic blood pressure, stroke volume, cerebral blood flow velocity and total peripheral resistance (p < 0.0054), in the COLD compared to ROOM conditions. CONCLUSIONS: In healthy controls, bolus cold water drinking results in favourable orthostatic cardiovascular responses during HUT/LBNP without significantly altering OT. Using a cold water bolus may result in additional benefits in patients with orthostatic intolerance above those conferred by bolus water at room temperature (by ameliorating orthostatic tachycardia and enhancing vascular resistance responses). Further research in patients with orthostatic intolerance is warranted.

Cardiovascular autonomic nervous system responses and orthostatic intolerance in astronauts and their relevance in daily medicine.

BACKGROUND: The harsh environmental conditions during space travel, particularly weightlessness, impose a major burden on the human body including the cardiovascular system. Given its importance in adjusting the cardiovascular system to environmental challenges, the autonomic nervous system has been in the focus of scientists and clinicians involved in human space flight. This review provides an overview on human autonomic research under real and simulated space conditions with a focus on orthostatic intolerance. METHODS: The authors conducted a targeted literature search using Pubmed. RESULTS: Overall, 120 articles were identified and included in the review. CONCLUSIONS: Postflight orthostatic intolerance is commonly observed in astronauts and could pose major risks when landing on another celestial body. The phenomenon likely results from changes in volume status and adaptation of the autonomic nervous system to weightlessness. Over the years, various non-pharmacological and pharmacological countermeasures have been investigated. In addition to enabling safe human space flight, this research may have implications for patients with disorders affecting cardiovascular autonomic control on Earth.

Sex Differences in Orthostatic Tolerance Are Mainly Explained by Blood Volume and Oxygen Carrying Capacity.

OBJECTIVES: The reduced orthostatic tolerance (OT) that is characteristic of the female sex may be explained by multiple phenotypic differences between sexes. This study aimed to elucidate the mechanistic role of blood volume (BV) and oxygen carrying capacity on sex differences in OT. DESIGN: Experimental intervention. SETTING: University of Calgary, Main Campus, Calgary, AB, Canada. SUBJECTS: Healthy women and men (n = 90) throughout the adult lifespan (20-89 yr) matched by age and physical activity. INTERVENTIONS: Incremental lower body negative pressure (LBNP) in all individuals. Blood withdrawal and oxygen carrying capacity reduction in men to match with women's levels. MEASUREMENTS AND MAIN RESULTS: Transthoracic echocardiography and central blood pressures were assessed throughout incremental LBNP for 1 hour or until presyncope. Blood uniformization resulted in a precise sex match of BV and oxygen carrying capacity (p ≥ 0.598). A third of women (14/45) and two thirds of men (31/45) prior to blood uniformization completed the orthostatic test without presyncopal symptoms (p-for-sex < 0.001). After blood uniformization, seven out of 45 men completed the test (p-for-sex = 0.081). Left ventricular end-diastolic volume (LVEDV) and stroke volume (SV) were progressively reduced with LBNP in both sexes, with women showing markedly lower volumes than men (p < 0.001). Blood uniformization did not eliminate sex differences in LVEDV and SV. CONCLUSIONS: Sex differences in OT are not present when BV and oxygen carrying capacity are experimentally matched between sexes throughout the adult lifespan.

Sex-Specific Effect of Blood Oxygen-Carrying Capacity on Orthostatic Tolerance in Older Individuals.

Blood oxygen (O2)-carrying capacity is reduced with aging and has been previously linked with the capacity to withstand the upright posture, that is, orthostatic tolerance (OT). This study experimentally tested the hypothesis that a definite reduction in blood O2-carrying capacity via hemoglobin manipulation differently affects the OT of older women and men as assessed by lower body negative pressure (LBNP). Secondary hemodynamic parameters were determined with transthoracic echocardiography throughout incremental LBNP levels for 1 hour or until presyncope in healthy older women and men (total n = 26) matched by age (64 ± 7 vs 65 ± 8 years, p < .618) and physical activity levels. Measurements were repeated within a week period after a 10% reduction of blood O2-carrying capacity via carbon monoxide rebreathing and analyzed via 2-way analysis of covariance. In the assessment session, OT time was similar between women and men (53.5 ± 6.1 vs 56.4 ± 6.0 minutes, p = .238). Following a 10% reduction of blood O2-carrying capacity, OT time was reduced in women compared with men (51.3 ± 7.0 vs 58.2 ± 2.8 minutes, p = .003). The effect of reduced O2-carrying capacity on OT time differed between sexes (mean difference [MD] = -5.30 minutes, p = .010). Prior to presyncope, reduced O2-carrying capacity resulted in lower left ventricular end-diastolic volume (MD = -8.11 mL∙m-2, p = .043) and stroke volume (MD = -8.04 mL∙m-2, 95% confidence interval = -14.36, -1.71, p = .018) in women relative to men, even after adjusting for baseline variables. In conclusion, present results suggest that reduced blood O2-carrying capacity specifically impairs OT and its circulatory determinants in older women.

Reliance on vascular responses for the maintenance of blood pressure in healthy older adults - Insights from the Valsalva maneuver.

Effective baroreflex-mediated cardiac and vascular resistance responses are crucial for homeostatic blood pressure control. We investigated the impacts of age and sex on arterial blood pressure regulation during a standard supine Valsalva maneuver (40 mmHg, 20s) in 46 healthy young and 25 healthy older adults. Noninvasive, continuous cardiovascular parameters were recorded. In older adults, cardiac output (older: -58.4 ± 2.4%; young: -40.8 ± 1.4%; p < 0.001) and stroke volume (older: -63.6 ± 2.6%; young: -48.7 ± 1.9%; p < 0.001) fell more than in young adults and was compensated by augmented vascular resistance responses (older: +189.8 ± 17.6%; young: +105.8 ± 6.7; p < 0.001); heart rate responses were attenuated in older adults. Male and female responses were comparable in their respective age groups.

The Influence of a Total Body Resistance Training Program on Autonomic Modulation and Strength Variables in Young Adults.

The purpose of this study was to examine autonomic modulation using multiple quantitative measures before and after a resistance training (RT) intervention. Seventeen young adults (age 18-35 years) were tested for body composition, muscular strength, and autonomic activity. The RT protocol targeted total-body large muscle groups, which were performed three days a week for eight-weeks. Autonomic assessments included respiratory sinus arrhythmia (RSA), static handgrip exercise, Valsalva maneuver, heart rate variability (HRV), and tilt-table testing. The main finding was that tilt-table duration increased by 68 seconds (p = 0.05) after RT. Upper body strength increased by 11.2 kg (p = 0.001) and lower body strength increased by 68.3 kg (p < 0.001) following completion of the RT intervention. The average total lean mass increased by 1.5 kg (p < 0.01), while total fat mass was unchanged (Δ = 0.5 kg, p = 0.23). RSA (Δ = 0.4, p = 0.89), Valsalva ratio (Δ = -0.09, p = 0.48), static handgrip (Δ = 8 mm Hg, p = 0.07), and HRV (Δ = -0.4, p = 0.53) were not affected by RT. The results from this study suggest that RT improves tilt-table tolerance in a young healthy population as evidence by improved tilt-table duration. However, RT seemed to have no effect on cardio-vagal or adrenergic function.

Forearm vascular resistance responses to the Valsalva maneuver in healthy young and older adults.

PURPOSE: Effective end-organ peripheral vascular resistance responses are critical to blood pressure control while upright, and prevention of syncope (fainting). The Valsalva maneuver (VM) induces blood pressure decreases that evoke baroreflex-mediated vasoconstriction. We characterized beat-to-beat forearm vascular resistance (FVR) responses to the VM in healthy adults, evaluated the impact of age and sex on these responses, and investigated their association with orthostatic tolerance (OT; susceptibility to syncope). We hypothesized that individuals with smaller FVR responses would be more susceptible to syncope. METHODS: Healthy young (N = 36; 19 women; age 25.4 ± 4.6 years) and older (N = 21; 12 women; age 62.4 ± 9.6 years) adults performed a supine 40 mmHg, 20 s VM. Graded 60° head-up-tilt with combined lower body negative pressure continued to presyncope was used to determine OT. Non-invasive beat-to-beat blood pressure and heart rate (finger plethysmography) were recorded continuously. FVR was calculated as mean arterial pressure (MAP) divided by brachial blood flow velocity (Doppler ultrasound) relative to baseline. RESULTS: The VM produces a distinctive FVR pattern that peaks (+137.1 ± 11.6%) in phase 2B (17.5 ± 0.3 s) as the baroreflex responds to low-pressure perturbations. This response increased with age overall (p < 0.001) and within male (p = 0.030) and female subgroups (p < 0.001). Maximum FVR during the VM was significantly correlated with maximal tilt FVR (r = 0.364; p = 0.0153) and with OT when expressed relative to the MAP decrease in phase 2A (Max FVR (%)/MAP2A-1; r = 0.337; p = 0.0206). CONCLUSION: This is the first characterization of FVR responses to the VM. The VM elicits large baroreflex-mediated increases in FVR; small FVR responses to the VM may indicate susceptibility to syncope.

Linking the hemodynamic consequences of adverse childhood experiences to an altered HPA axis and acute stress response.

Adverse childhood experiences (ACEs), such as maltreatment and severe household dysfunction, represent a significant threat to public health as ACEs are associated with increased prevalence of several chronic diseases. Biological embedding, believed to be rooted in dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis, is the prevailing theory by which chronic diseases become imprinted in individuals following childhood adversity. A shift towards HPA axis hypoactivity occurs in response to ACEs exposure and is proposed to contribute towards altered cortisol secretion, chronic low-grade inflammation, and dysregulated hemodynamic and autonomic function. This shift in HPA axis activity may be a long-term effect of glucocorticoid receptor methylation with downstream effects on hemodynamic and autonomic function. Emerging evidence suggests syncopal tendencies are increased among those with ACEs and coincides with altered neuroimmune function. Similarly, chronic low-grade inflammation may contribute towards arterial baroreceptor desensitization through increased arterial stiffness, negatively impacting autonomic regulation following posture change and increasing rates of syncope in later life, as has been previously highlighted in the literature. Although speculative, baroreceptor desensitization may be secondary to increased arterial stiffness and changes in expression of glucocorticoid receptors and arginine vasopressin, which are chronically altered by ACEs. Several research gaps and opportunities exist in this field and represent prospective areas for future investigation. Here, we synthesize current findings in the areas of acute psychosocial stress reactivity pertaining to HPA axis function, inflammation, and hemodynamic function while suggesting ideas for future research emphasizing systemic interactions and postural stress assessments among those with ACEs. This review aims to identify specific pathways which may contribute towards orthostatic intolerance in populations with history of childhood adversity.

Efficacy of Gradient Compression Garments in the Hours After Long-Duration Spaceflight.

The incidence of presyncopal events is high soon after a long-duration spaceflight;>60% of returning astronauts could not complete a 10-min 80° head-up tilt test on landing day (R+0) after ~6 months of spaceflight. The objective of this study was to demonstrate the ability of a lower body gradient compression garment (GCG) to protect against an excessive increase in heart rate and a decrease in blood pressure during standing after long-duration spaceflight. Methods: Eleven astronauts (9 M, 2 F) volunteered to participate. The stand test protocol consisted of 2 min of prone rest followed by 3.5 min of standing. Subjects completed one familiarization session, two preflight data collection sessions in standard clothing, and three tests on landing day while wearing GCG. Postflight tests were conducted 1-4 h (R+0A), ~12 h (R+0B), and ~28 h after landing (R+0C). Results: All astronauts completed the stand test preflight. Three astronauts were unable to attempt the stand test at R+0A, and one of these was unable to start the test at R+0B. One astronaut was unable to complete 3.5 min of standing at R+0B (test ended at 3.3 min). Review of the individual's blood pressure data revealed no hypotension but the astronaut reported significant motion sickness. Of the astronauts who participated in testing on landing day, the heart rate and mean arterial pressure responses to standing (stand-prone) were not different than preflight at any of the postflight sessions. Conclusion: Wearing the GCG after spaceflight prevented the tachycardia that normally occurs while standing after spaceflight without compression garments and protected against a decrease in blood pressure during a short stand test.

MNX (Medium Duration Nutrition and Resistance-Vibration Exercise) Bed-Rest: Effect of Resistance Vibration Exercise Alone or Combined With Whey Protein Supplementation on Cardiovascular System in 21-Day Head-Down Bed Rest.

Current inflight countermeasures do not completely prevent bone and cardiovascular changes induced by microgravity. High load Resistance Exercise combined with whole body Vibration (RVE) demonstrated benefits on bone and cardiovascular system during previous Head-Down Bed Rest (HDBR) studies. We examined the effectiveness of RVE alone or combined with a nutritional supplementation of Whey protein (NeX) on cardiovascular deconditioning. Eight male subjects (age 34 ± 8 years) in a crossover design completed three 21-day HDBR campaigns (Control-CON, RVE, and NeX). Pre and post HDBR Orthostatic Tolerance (OT) was evaluated by a 15-min head-up tilt test followed by increasing levels of Lower Body Negative Pressure (LBNP). Heart rate (HR), blood pressure (BP), and Sympathetic Index (ΣI) through spectral analysis were measured during OT test. Plasma Volume (PV), and Maximal Oxygen Uptake (VO2max) were measured before and after each campaign. Left ventricular mass, left ventricular end diastolic (LVEDV), end systolic (LVESV), stroke (SV) volumes, and circumferential deformation at rest and during an orthostatic stress simulated by a 30 mmHg LBNP were measured by cardiac MRI. RVE failed to prevent any change in these variables and NeX did not have any additional effect over exercise alone. In the 3 groups, (1) OT time dropped similarly (bed rest p < 0.001), (2) HR and ΣI were increased at rest at the end of HDBR and HR increased markedly during LBNP-tilt test, with inability to increase further the ΣI, (3) PV dropped (bed rest p < 0.001), along with LVEDV, LVESV and SV (p = 0.08, p < 0.001, and p = 0.045, respectively), (4) Left ventricle mass did not change significantly, (5) Deformation of the heart assessed by global circumferential strain was preserved and early diastolic circumferential strain rate was increased during orthostatic stress at the end of HDBR, illustrating preserved systolic and diastolic function respectively, without any difference between groups. Despite the drop in PV and LV volumes, RVE and NeX tended to alleviate the decrease in VO2max. In conclusion, RVE and NeX failed to prevent the cardiovascular deconditioning induced by a 21 day-HDBR.

Lower-limb venous distension reflex and orthostatic tolerance in young healthy humans.

Earlier reports suggest that limb venous distension evokes reflex increases in muscle sympathetic nerve activity (MSNA) and blood pressure (BP) (i.e., venous distension reflex). Our recent report also shows that suction of arterially occluded limb evokes venous distension reflex. We postulate that the venous distension reflex contributes to autonomic responses to orthostatic stress. In this study, we hypothesized that orthostatic tolerance would be linked to the MSNA response seen with lower limb suction. Fifteen healthy subjects were tested in the supine position. Negative pressure (-100 mmHg) was applied on an arterially occluded lower limb for 2 min. MSNA from the peroneal nerve in the limb not exposed to suction, ECG, and BP (Finometer) was recorded throughout the study. Limb occlusion without suction was used as a control trial. In a separate visit, the individual's orthostatic tolerance was assessed using a graded lower body negative pressure (LBNP) tolerance test. Mean arterial BP and MSNA (18.6 ± 1.9 to 23.6 ± 2.0 bursts/min) significantly (both P < 0.05) increased during limb suction. Orthostatic tolerance index positively correlated (R = 0.636, P = 0.011) with the MSNA response seen with suction during occlusion. Since the venous distension reflex strength correlates with the level of orthostatic tolerance, we speculate that lower-limb venous distension reflex engagement increases the sympathetic responses during orthostatic challenge and serves to maintain BP with postural stress.

Cardiovascular System Under Simulated Weightlessness: Head-Down Bed Rest vs. Dry Immersion.

BACKGROUND: The most applicable human models of weightlessness are -6° head-down bed rest (HDBR) and head-out dry immersion (DI). A detailed experimental comparison of cardiovascular responses in both models has not yet been carried out, in spite of numerous studies having been performed in each of the models separately. OBJECTIVES: We compared changes in central hemodynamics, autonomic regulation, plasma volume, and water balance induced by -6° HDBR and DI. METHODS: Eleven subjects participated in a 21-day HDBR and 12 subjects in a 3-day DI. During exposure, measurements of the water balance, blood pressure, and heart rate were performed daily. Plasma volume evolution was assessed by the Dill-Costill method. In order to assess orthostatic tolerance time (OTT), central hemodynamic responses to orthostatic stimuli, and autonomous regulation, the 80° lower body negative pressure-tilt test was conducted before and right after both exposures. RESULTS: For most of the studied parameters, the changes were co-directional, although they differed in their extent. The changes in systolic blood pressure and total peripheral resistance after HDBR were more pronounced than those after DI. The OTT was decreased in both groups: to 14.2 ± 3.1 min (vs. 27.9 ± 2.5 min before exposure) in the group of 21-day HDBR and to 8.7 ± 2.1 min (vs. 27.7 ± 1.2 min before exposure) in the group of 3-day DI. CONCLUSIONS: In general, cardiovascular changes during the 21-day HDBR and 3-day DI were co-directional. In some cases, changes in the parameters after 3-day DI exceeded changes after the 21-day HDBR, while in other cases the opposite was true. Significantly stronger effects of DI on cardiovascular function may be due to hypovolemia and support unloading (supportlessness).

An assessment of hypercapnia-induced elevations in regional cerebral perfusion during combined orthostatic and heat stresses.

We investigated that the effects of hypercapnia-induced elevations in cerebral perfusion during a heat stress on global cerebrovascular responses to an orthostatic challenge. Seven volunteers completed a progressive lower-body negative pressure (LBNP) challenge to presyncope during heat stress, with or without breathing a hypercapnic gas mixture. Administration of the hypercapnic gas mixture increased the partial pressure of end-tidal CO2 greater than pre-heat stress alone, and increased both internal carotid artery (ICA) and vertebral artery (VA) blood flows (P < 0.05). During LBNP, both ICA and VA blood flows with the hypercapnic gas mixture remained elevated relative to the control trial (P < 0.05). However, at the end of LBNP due to pre-syncopal symptoms, both ICA and VA blood flows decreased to similar levels between trials. These findings suggest that hypercapnia-induced cerebral vasodilation is insufficient to maintain cerebral perfusion at the end of LBNP due to pre-syncope in either the anterior or posterior vascular beds.

DI-5-CUFFS: Venoconstrictive Thigh Cuffs Limit Body Fluid Changes but Not Orthostatic Intolerance Induced by a 5-Day Dry Immersion.

Venoconstrictive thigh cuffs are used by cosmonauts to ameliorate symptoms associated with cephalad fluid shift. A ground simulation of microgravity, using the dry immersion (DI) model, was performed to assess the effects of thigh cuffs on body fluid changes and dynamics, as well as on cardiovascular deconditioning. Eighteen healthy men (25-43 years), randomly divided into two groups, (1) control group or (2) group with thigh cuffs worn 10 h/day, underwent 5-day DI. Cardiovascular responses to orthostatic challenge were evaluated using the lower body negative pressure (LBNP) test; body fluid changes were assessed by bio-impedance and hormonal assay; plasma volume evolution was estimated using hemoglobin-hematocrit; subjective tolerance was assessed by questionnaires. DI induced a decrease in plasma volume of 15-20%. Reduction in total body water of 3-6% stabilized toward the third day of DI. This reduction was derived mostly from the extracellular compartment. During the acute phase of DI, thigh cuffs limited the decrease in renin and the increase in N-terminal prohormone of brain natriuretic peptide (NT-proBNP), the loss in total body water, and tended to limit the loss in calf volume, extracellular volume and plasma volume. At the later stable phase of DI, a moderate protective effect of thigh cuffs remained evident on the body fluids. Orthostatic tolerance time dropped after DI without significant difference between groups. Thigh cuff countermeasure slowed down and limited the loss of body water and tended to limit plasma loss induced by DI. These observed physiological responses persisted during periods when thigh cuffs were removed. However, thigh cuffs did not counteract decreased tolerance to orthostatic challenge.

Cardiovascular regulation: associations between exercise and head-up tilt.

It was hypothesized that faster cardiorespiratory kinetics during exercise are associated with higher orthostatic tolerance. Cardiorespiratory kinetics of 14 healthy male subjects (30 ± 4 years, 179 ± 8 cm, 79 ± 8 kg) were tested on a cycle ergometer during exercise with changing work rates of 30 and 80 W. Pulmonary oxygen uptake ( ) was measured breath-by-breath and heart rate (HR), mean arterial blood pressure (MAP), and total peripheral resistance (TPR) were measured beat-to-beat. Muscular oxygen uptake ( ) was estimated from HR and . Kinetic parameters were determined by time-series analysis, using cross-correlation functions (CCFmax(x)) between the parameter and the work rate. Cardiovascular regulations of MAP, HR, and TPR during orthostatic stress were measured beat-to-beat on a tilt seat. Changes between the minima and maxima during the 6° head-down tilt and the 90° head-up tilt positions were calculated for each parameter (Δtilt-up). correlated significantly with ΔTPRtilt-up (r = 0.790, p ≤ 0.001). CCFmax(HR) was significantly correlated with ΔHRtilt-up (r = -0.705, p = 0.002) and the amplitude in HR from 30 to 80 W (rSP = -0.574, p = 0.016). The observed correlations between cardiorespiratory regulation in response to exercise and orthostatic stress during rest might allow for a more differential analysis of the underlying mechanisms of orthostatic intolerance in, for example, patient groups.

Age-dependent impairment of the erythropoietin response to reduced central venous pressure in HFpEF patients.

Despite growing research interest in the pathophysiology of heart failure with preserved ejection fraction (HFpEF), it remains unknown whether central hemodynamic alterations inherently present in this condition do affect blood pressure and blood volume (BV) regulation. The present study sought to determine hemodynamic and endocrine responses to prolonged orthostatic stress in HFpEF patients. Central venous pressure (CVP) assessed via the internal jugular vein (IJV) aspect ratio with ultrasonography, arterial pressure and heart rate were determined at supine rest and during 2 hours of moderate (25-30°) head-up tilt (HUT) in 18 stable HFpEF patients (71.2 ± 7.3 years), 14 elderly (EC), and 10 young (YC) healthy controls. Parallel endocrine measurements comprised main BV-regulating hormones: pro-atrial natriuretic peptide, copeptin, aldosterone, and erythropoietin (EPO). At supine rest, the IJV aspect ratio was higher (>30%) in HFpEF patients compared with EC and YC, while mean arterial pressure was elevated in HFpEF patients (98.0 ± 13.1 mm Hg) and EC (95.6 ± 8.3 mm Hg) versus YC (87.3 ± 5.0 mm Hg) (P < 0.05). HUT increased heart rate (+10%) and reduced the IJV aspect ratio (-52%), with similar hemodynamic effects in all groups (P for interaction ≥ 0.322). The analysis of endocrine responses to HUT revealed a group×time interaction for circulating EPO, which was increased in YC (+10%) but remained unaltered in HFpEF patients and EC. The EPO response to a given reduction in CVP is similarly impaired in HFpEF patients and elderly controls, suggesting an age-dependent dissociation of EPO production from hemodynamic regulation in the HFpEF condition.