Search

We hypothesized that exposure to prolonged recumbency (bedrest), and thus reductions of intravascular pressure gradients, increases pressure distension in arteries/arterioles in the legs. Ten subjects underwent 5 wk of horizontal bedrest. Pressure distension was investigated in arteries and arterioles before and after the bedrest, with the subject seated or supine in a hyperbaric chamber with either one arm or a lower leg protruding through a hole in the chamber door. Increased pressure in the vessels of the arm/leg was accomplished by increasing chamber pressure. Vessel diameter and flow were measured in the brachial and posterior tibial arteries using Doppler ultrasonography. Electrical tissue impedance was measured in the test limb. Bedrest increased (P < 0.01) pressure distension threefold in the tibial artery (from 8 [+ or -] 7% to 24 [+ or -] 11%) and by a third (P < 0.05) in the brachial artery (from 15 [+ or -] 9% to 20 [+ or -] 10%). The pressure-induced increase in tibial artery flow was more pronounced (P < 0.01) after (50 [+ or -] 39 ml/min) than before (13 [+ or -] 23 ml/min) bedrest, whereas the brachial artery flow response was unaffected by bedrest. The pressure-induced decrease in tissue impedance in the leg was more pronounced (P < 0.01) after (16 [+ or -] 7%) than before (10 [+ or -] 6%) bedrest, whereas bedrest did not affect the impedance response in the arm. Thus, withdrawal of the hydrostatic pressure gradients that act along the blood vessels in erect posture markedly increases pressure distension in dependent arteries and arterioles. gravity; microgravity; vascular compliance; vascular deconditioning; vascular stiffness

To gain insights into microgravity-induced ophthalmic changes (microgravity ocular syndrome), and as part of a project investigating effects of future planetary habitats, we investigated the effect of acute hypercapnia following 10-day bed rest and hypoxia on posterior eye structures. Female subjects (N = 7) completed three 10-day experimental interventions: 1) normoxic bed rest [NBR; partial pressure of inspired O2 (PIO2) 132.9 ± 0.3 Torr]; 2) hypoxic ambulatory confinement (HAMB; PIO2 =90.4 ± 0.3 Torr); and 3) hypoxic bed rest (HBR; n = 12; PIO2 = 90.4 ± 0.3 Torr). Before and on the last day of each intervention, optical coherence tomography (OCT) of the optic disk was performed, and the thicknesses of the retinal nerve fiber layer (RNFL), retina, and choroid were measured. OCT examinations were conducted with the subjects breathing the prevailing normocapnic breathing mixture (either normoxic or hypoxic) and then following a 10-min period of breathing the same gas mixture, but with the addition of 1% CO2. Choroidal thickness was greater during both bed-rest conditions (NBR and HBR) compared with the ambulatory (HAMB) condition (ANOVA, P < 0.001). Increases in RNFL thickness compared with baseline were observed in the hypoxic trials (HBR, P < 0.001; and HAMB, P = 0.021), but not the normoxic trial (NBR). A further increase in RNFL thickness (P = 0.019) was observed after the 10-min hypercapnic trial in the NBR condition only. The fact that choroidal thickness was not affected by PO2 or PCO2, but increased by bed rest, suggests a hydrostatic rather than a vasoactive effect. The increments in RNFL thickness were most likely associated with local hypoxia and hypercapnia-induced dilatation of the retinal blood vessels. [ABSTRACT FROM AUTHOR]

Without visual references, nonpilots exposed to coordinated flight turns underestimate the bank angle, because of discordant information of the roll-angular displacement from the otoliths, consistently signaling vertical position, versus the semicircular canals, enabling detection of the displacement. Pilots may also use their ability to perceive the G load and knowledge of the relation between load and angle to assess the bank angle. Our aim was to investigate whether the perception of bank angle can be improved by spatial orientation training in a centrifuge. Sixteen pilots/pilot students assessed their roll tilt, in complete darkness, during both real coordinated flight turns and gondola centrifugation, at roll tilts of 30° and 60°. The experiments were repeated after a 3-wk period, during which eight of the subjects performed nine training sessions in the centrifuge, comprising feedback on roll angle vs. G load, and on indicating requested angles. Before training, the subjects perceived in the aircraft and centrifuge, respectively: 37 (17)°, 38 (14)° during 60° turns and 19 (12)°, 20 (10)° during 30° turns. Training improved the perception of angle during the 60° [to 60 (7)°, 55 (10)°; P ≤ 0.04] but not the 30° [21 (10)°, 15 (9)°; P ≥ 0.30] turns; the improvement disappeared within 2 yr after training. Angle assessments did not change in the untrained group. The results suggest that it is possible to, in a centrifuge, train a pilot's ability to perceive large but not discrete-to-moderate roll-angular displacements. The transient training effect is attributable to improved capacity to perceive and translate G load into roll angle and/or to increased reliance on semicircular canal signals. NEW & NOTEWORTHY Spatial disorientation is a major problem in aviation. When performing coordinated flight turns without external visual cues (e.g., flying in clouds or darkness), the pilot underestimates the aircraft bank angle because the vestibular system provides unreliable information of roll tilt. The present study demonstrates that it is possible to, in a long-arm centrifuge, train a pilot's ability to perceive large but not discrete-to-moderate roll-angular displacements.

Breath-holding preceded by either an overnight fast or hyperventilation has been shown to potentiate the risk of a hypoxic blackout. However, no study has explored the combined effects of fasting and hyperventilation on apneic performance and associated physiological responses. Nine nondivers (8 males) attended the laboratory on two separate occasions (≥48 h apart), both after a 12-h overnight fast. During each visit, a hyperoxic rebreathing trial was performed followed by three repeated maximal static apneas preceded by either normal breathing (NORM) or a 30-s hyperventilation (HYPER). Splenic volume, hematology, cardiovascular, and respiratory variables were monitored. There were no interprotocol differences at rest or during hyperoxic rebreathing for any variable ( P ≥ 0.09). On nine occasions (8 in HYPER), the subjects reached our safety threshold (oxygen saturation 65%) and were asked to abort their apneas, with the preponderance of these incidents (6 of 9) occurring during the third repetition. Across the sequential attempts, longer apneas were recorded in HYPER [median(range), 220(123-324) s vs. 185(78-296) s, P ≤ 0.001], with involuntary breathing movements occurring later [134(65-234) s vs. 97(42-200) s, P ≤ 0.001] and end-apneic partial end-tidal pressures of oxygen ( P ET O 2 ) being lower ( P ≤ 0.02). During the final repetition, partial end-tidal pressure of carbon dioxide [( P ET CO 2 ), 6.53 ± 0.46 kPa vs. 6.01 ± 0.45 kPa, P = 0.005] was lower in HYPER. Over the serial attempts, preapneic tidal volume was gradually elevated [from apnea 1 to 3 , by 0.26 ± 0.24 L (HYPER) and 0.28 ± 0.30 L (NORM), P ≤ 0.025], with a correlation noted with preapneic P ET CO 2 ( r = -0.57, P < 0.001) and P ET O 2 ( r = 0.76, P < 0.001), respectively. In a fasted state, preapnea hyperventilation compared with normal breathing leads to longer apneas but may increase the susceptibility to a hypoxic blackout. NEW & NOTEWORTHY This study shows that breath-holds (apneas) preceded by a 12-h overnight fast coupled with a 30-s hyperventilation as opposed to normal breathing may increase the likelihood of a hypoxic blackout through delaying the excitation of hypercapnic ventilatory sensory chemoreflexes. Evidently, this risk is exacerbated over a series of repeated maximal attempts, possibly due to a shift in preapneic gas tensions facilitated by an unintentional increase in tidal volume breathing.

The study examined intra- and interlimb variations in cutaneous vessel responsiveness to acute and repeated transmural pressure elevations. In 11 healthy men, red blood cell flux was assessed via laser-Doppler flowmetry on both glabrous and nonglabrous skin regions of an arm (finger and forearm) and leg (toe and lower leg), across a wide range of stepwise increasing distending pressures imposed in the vessels of each limb separately. The pressure-flux cutaneous responses were evaluated before and after 5 wk of intermittent (40 min, 3 sessions per week) exposures to hypergravity (∼2.6-3.3 G; G training). Before and after G training, forearm and lower leg blood flux were relatively stable up to ∼210 and ∼240 mmHg distending pressures, respectively; and then they increased two- to threefold ( P < 0.001). Finger blood flux dropped promptly ( P < 0.001), regardless of the G training ( P = 0.64). At ≤120-mmHg distending pressures, toe blood flux enhanced by ∼40% ( P ≤ 0.05); the increase was augmented after the G training ( P = 0.01). At high distending pressures, toe blood flux dropped by ∼70% in both trials ( P < 0.001). The present results demonstrate that circulatory autoregulation is more pronounced in glabrous skin than in nonglabrous skin, and in nonglabrous sites of the leg than in those of the arm. Repetitive high-sustained gravitoinertial stress does not modify the pressure-flow relationship in the dependent skin vessels of the arm nor in the nonglabrous sites of the lower leg. Yet it may partly inhibit the myogenic responsiveness of the toe's glabrous skin.

We sought to examine whether short-term, whole body cold acclimation would modulate finger vasoreactivity and thermosensitivity to localized cooling. Fourteen men were equally assigned to either the experimental (CA) or the control (CON) group. The CA group was immersed to the chest in 14°C water for ≤120 min daily over a 5-day period while the skin temperature of the right-hand fingers was clamped at ∼35.5°C. The CON group was instructed to avoid any cold exposure during this period. Before and after the intervention, both groups performed, on two different consecutive days, a local cold provocation trial consisting of a 30-min hand immersion in 8°C water while immersed to the chest once in 21°C (mild-hypothermic trial; 0.5°C fall in rectal temperature from individual preimmersion values) and on the other occasion in 35.5°C (normothermic trial). In the CA group, the cold-induced reduction in finger temperature was less (mild-hypothermic trial: P = 0.05; normothermic trial: P = 0.02), and the incidence of the cold-induced vasodilation episodes was greater (in normothermic trials: P = 0.04) in the post- than in the preacclimation trials. The right-hand thermal discomfort was also attenuated (mild-hypothermic trial: P = 0.04; normothermic trial: P = 0.01). The finger temperature responses of the CON group did not vary between testing periods. Our findings suggest that repetitive whole body exposure to severe cold within a week may attenuate finger vasoreactivity and thermosensitivity to localized cooling. These regional thermo-adaptions were ascribed to central neural habituation produced by the iterative, generalized cold stimulation.

Despite decades of experience from high-gravitoinertial (G) exposures in aircraft and centrifuges, information is scarce regarding primary cardiovascular adaptations to +Gz loads in relaxed humans. Thus, effects of G-training are typically evaluated after regimens that are confounded by concomitant use of anti-G straining maneuvers, anti-G suits, and pressure breathing. Accordingly, the aim was to evaluate cardiovascular adaptations to repeated +Gz exposures in the relaxed state. Eleven men underwent 5 wk of centrifuge G training, consisting of 15 × 40 min +Gz exposures at G levels close to their individual relaxed G-level tolerance. Before and after the training regimen, relaxed G-level tolerance was investigated during rapid onset-rate (ROR) and gradual onset-rate (GOR) G exposures, and cardiovascular responses were investigated during orthostatic provocation and vascular pressure-distension tests. The G training resulted in: 1 ) a 13% increase in relaxed ROR G tolerance ( P < 0.001), but no change in GOR G tolerance, 2 ) increased pressure resistance in the arteries and arterioles of the legs ( P < 0.001), but not the arms, and 3 ) a reduced initial drop in arterial pressure upon ROR high G, but no change in arterial pressure under basal resting conditions or during GOR G loading, or orthostatic provocation. The results suggest +Gz adaptation via enhanced pressure resistance in dependent arteries/arterioles. Presumably, this reflects local adaptations to high transmural pressures, resulting from the +Gz-induced exaggeration of the intravascular hydrostatic pressure gradients.

This retrospective study was designed to analyze the interindividual variability in the responses of different variables characterizing the skeletal muscle oxidative function to normoxic (N-BR) and hypoxic (H-BR) bed rests and to a hypoxic ambulatory confinement (H-AMB) of 10 and 21 days. We also assessed whether and how the addition of hypoxia to bed rest might influence the heterogeneity of the responses. In vivo measurements of O 2 uptake and muscle fractional O 2 extraction were carried out during an incremental one-leg knee-extension exercise. Mitochondrial respiration was assessed in permeabilized muscle fibers. A total of 17 subjects were included in this analysis. This analysis revealed a similar variability among subjects in the alterations induced by N-BR and H-BR both in peak O 2 uptake (SD: 4.1% and 3.3% after 10 days; 4.5% and 8.1% after 21 days, respectively) and peak muscle fractional O 2 extraction (SD: 5.9% and 7.3% after 10 days; 6.5% and 7.3% after 21 days), independently from the duration of the exposure. The individual changes measured in these variables were significantly related ( r = 0.66, P = 0.004 after N-BR; r = 0.61, P = 0.009 after H-BR). Mitochondrial respiration showed a large variability of response after both N-BR (SD: 25.0% and 15.7% after 10 and 21 days) and H-BR (SD: 13.0% and 19.8% after 10 and 21 days); no correlation was found between N-BR and H-BR changes. When added to bed rest, hypoxia altered the individual adaptations within the mitochondria but not those intrinsic to the muscle oxidative function in vivo, both after the short- and medium-term exposures.

We examined the in vivo pressure-flow relationship in human cutaneous vessels during acute and repeated elevations of local transmural pressure. In 10 healthy men, red blood cell flux was monitored simultaneously on the nonglabrous skin of the forearm and the glabrous skin of a finger during a vascular pressure provocation, wherein the blood vessels of an arm were exposed to a wide range of stepwise increasing distending pressures. Forearm skin blood flux was relatively stable at slight and moderate elevations of distending pressure, whereas it increased approximately three- to fourfold at the highest levels ( P = 0.004). Finger blood flux, on the contrary, dropped promptly and consistently throughout the provocation ( P < 0.001). Eight of the subjects repeated the provocation trial after a 5-wk pressure-training regimen, during which the vasculature in one arm was exposed intermittently (40 min, 3 times/wk) to increased transmural pressure (from +65 mmHg week 1 to +105 mmHg week 5 ). The training regimen diminished the pressure-induced increase in forearm blood flux by ∼34% ( P = 0.02), whereas it inhibited the reduction in finger blood flux ( P < 0.001) in response to slight and moderate distending pressure elevations. The present findings demonstrate that during local pressure perturbations, the cutaneous autoregulatory function is accentuated in glabrous compared with in the nonglabrous skin regions. Prolonged intermittent regional exposures to augmented intravascular pressure blunt the responsiveness of the glabrous skin but enhance arteriolar pressure resistance in the nonglabrous skin.

We examined the interactive effects of mild hypothermia and hypoxia on finger vasoreactivity to local cold stress. Eight male lowlanders performed, in a counterbalanced order, a normoxic and a hypoxic (partial pressure of oxygen: ~12 kPa) hand cold provocation (consisting of a 30-min immersion in 8°C water), while immersed to the chest either in 21°C [cold trials; 0.5°C fall in rectal temperature (T rec ) from individual preimmersion values], or in 35.5°C water, or while exposed to 27°C air. The duration of the trials was kept constant in each breathing condition. Physiological (T rec , skin temperature, cutaneous vascular conductance, oxygen uptake) and perceptual (thermal sensation and comfort, local pain, affective valence) reactions were monitored continually. Hypoxia accelerated the drop in T rec by ~14 min ( P = 0.06, d  = 0.67). In the air-exposure trials, hypoxia did not alter finger perfusion during the local cooling, whereas it impaired the finger rewarming response following the cooling ( P < 0.01). During the 35.5°C immersion, the finger vasomotor tone was enhanced, especially in hypoxia ( P = 0.01). Mild hypothermia aggravated finger vasoconstriction instigated by local cooling ( P < 0.01), but the response did not differ between the two breathing conditions ( P > 0.05). Hypoxia tended to attenuate the sensation of coldness ( P = 0.10, r  = 0.40) and thermal discomfort ( P = 0.09, r  = 0.46) in the immersed hand. Both in normoxia and hypoxia, the whole body thermal state dictates the cutaneous vasomotor reactivity to localized cold stimulus.

Our understanding of skeletal muscle structural and functional alterations during unloading has increased in recent decades, yet the molecular mechanisms underpinning these changes have only started to be unraveled. The purpose of the current investigation was to assess changes in skeletal muscle gene expression after 21 days of bed rest, with a particular focus on predicting upstream regulators of muscle disuse. Additionally, the association between differential microRNA expression and the transcriptome signature of bed rest were investigated. mRNAs from musculus vastus lateralis biopsies obtained from 12 men before and after the bed rest were analyzed using a microarray. There were 54 significantly upregulated probesets after bed rest, whereas 103 probesets were downregulated (false discovery rate 10%; fold-change cutoff ≥1.5). Among the upregulated genes, transcripts related to denervation-induced alterations in skeletal muscle were identified, e.g., acetylcholine receptor subunit delta and perinatal myosin. The most downregulated transcripts were functionally enriched for mitochondrial genes and genes involved in mitochondrial biogenesis, followed by a large number of contractile fiber components. Upstream regulator analysis identified a robust inhibition of the myocyte enhancer factor-2 (MEF2) family, in particular MEF2C, which was suggested to act upstream of several key downregulated genes, most notably peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α)/peroxisome proliferator-activated receptors (PPARs) and CRSP3. Only a few microRNAs were identified as playing a role in the overall transcriptome picture induced by sustained bed rest. Our results suggest that the MEF2 family is a key regulator underlying the transcriptional signature of bed rest and, hence, ultimately also skeletal muscle alterations induced by systemic unloading in humans.

The study examined the effects of hypoxia and horizontal bed rest, separately and in combination, on peak oxygen uptake (V̇o2 peak) during upright cycle ergometry. Ten male lowlanders underwent three 21-day confinement periods in a counterbalanced order: 1) normoxic bed rest [NBR; partial pressure of inspired O2 (PiO2 ) = 133.1 ± 0.3 mmHg]; 2) hypoxic bed rest (HBR; PiO2 = 90.0 ± 0.4 mmHg), and 3) hypoxic ambulation (HAMB; PiO2 = 90.0 ± 0.4 mmHg). Before and after each confinement, subjects performed two incremental-load trials to exhaustion, while inspiring either room air (AIR), or a hypoxic gas (HYPO; PiO2 = 90.0 ± 0.4 mmHg). Changes in regional oxygenation of the vastus lateralis muscle and the frontal cerebral cortex were monitored with near-infrared spectroscopy. Cardiac output (CO) was recorded using a bioimpedance method. The AIR V̇o2 peak was decreased by both HBR (∼13.5%; P ≤ 0.001) and NBR (∼8.6%; P ≤ 0.001), with greater drop after HBR (P = 0.01). The HYPO V̇o2 peak was also reduced by HBR (-9.7%; P ≤ 0.001) and NBR (-6.1%; P ≤ 0.001). Peak CO was lower after both bed-rest interventions, and especially after HBR (HBR: ∼13%, NBR: ∼7%; P ≤ 0.05). Exercise-induced alterations in muscle and cerebral oxygenation were blunted in a similar manner after both bed-rest confinements. No changes were observed in HAMB. Hence, the bed-rest-induced decrease in V̇o2 peak was exaggerated by hypoxia, most likely due to a reduction in convective O2 transport, as indicated by the lower peak values of CO., (Copyright © 2016 the American Physiological Society.)

It is known that arterial pressure correlates positively with body height in males, and it has been suggested that this is due to the increasing vertical hydrostatic gradient from the heart to the carotid baroreceptors. Therefore, we tested the hypothesis that a higher gravito-inertial stress induced by the use of a human centrifuge would increase mean arterial pressure (MAP) more in tall than in short males in the seated position. In short (162-171 cm; n = 8) and tall (194-203 cm; n = 10) healthy males (18-41 yr), brachial arterial pressure, heart rate (HR), and cardiac output were measured during +2G centrifugation, while they were seated upright with the legs kept horizontal (+2Gz). In a separate experiment, the same measurements were done with the subjects supine (+2Gx). During +2Gz MAP increased in the short (22 ± 2 mmHg, P < 0.0001) and tall (23 ± 2 mmHg, P < 0.0001) males, with no significant difference between the groups. HR increased more (P < 0.05) in the tall than in the short group (14 ± 2 vs. 7 ± 2 bpm). Stroke volume (SV) decreased in the short group (26 ± 4 ml, P = 0.001) and more so in the tall group (39 ± 5 ml, P < 0.0001; short vs. tall, P = 0.047). During +2Gx, systolic arterial pressure increased (P < 0.001) and SV (P = 0.012) decreased in the tall group only. In conclusion, during +2Gz, MAP increased in both short and tall males, with no difference between the groups. However, in the tall group, HR increased more during +2Gz, which could be caused by a larger hydrostatic pressure gradient from heart to head, leading to greater inhibition of the carotid baroreceptors., (Copyright © 2015 the American Physiological Society.)