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  • 1. Debevec, T.
    et al.
    Ganse, B.
    Mittag, U.
    Eiken, Ola
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Swedish Aerospace Physiology Centre, SAPC.
    Mekjavic, I. B.
    Rittweger, J.
    Hypoxia aggravates inactivity-Related muscle wasting2018In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 9, no May, article id 494Article in journal (Refereed)
    Abstract [en]

    Poor musculoskeletal state is commonly observed in numerous clinical populations such as chronic obstructive pulmonary disease (COPD) and heart failure patients. It, however, remains unresolved whether systemic hypoxemia, typically associated with such clinical conditions, directly contributes to muscle deterioration. We aimed to experimentally elucidate the effects of systemic environmental hypoxia upon inactivity-related muscle wasting. For this purpose, fourteen healthy, male participants underwent three 21-day long interventions in a randomized, cross-over designed manner: (i) bed rest in normoxia (NBR; PiO2 = 133.1 ± 0.3 mmHg), (ii) bed rest in normobaric hypoxia (HBR; PiO2 = 90.0 ± 0.4 mmHg) and ambulatory confinement in normobaric hypoxia (HAmb; PiO2 = 90.0 ± 0.4 mmHg). Peripheral quantitative computed tomography and vastus lateralis muscle biopsies were performed before and after the interventions to obtain thigh and calf muscle cross-sectional areas and muscle fiber phenotype changes, respectively. A significant reduction of thigh muscle size following NBR (-6.9%, SE 0.8%; P < 0.001) was further aggravated following HBR (-9.7%, SE 1.2%; P = 0.027). Bed rest-induced muscle wasting in the calf was, by contrast, not exacerbated by hypoxic conditions (P = 0.47). Reductions in both thigh (-2.7%, SE 1.1%, P = 0.017) and calf (-3.3%, SE 0.7%, P < 0.001) muscle size were noted following HAmb. A significant and comparable increase in type 2× fiber percentage of the vastus lateralis muscle was noted following both bed rest interventions (NBR = +3.1%, SE 2.6%, HBR = +3.9%, SE 2.7%, P < 0.05). Collectively, these data indicate that hypoxia can exacerbate inactivity-related muscle wasting in healthy active participants and moreover suggest that the combination of both, hypoxemia and lack of activity, as seen in COPD patients, might be particularly harmful for muscle tissue.

  • 2.
    Gennser, Mikael
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Swedish Aerospace Physiology Centre, SAPC.
    Blogg, S. L.
    SLB Consulting, Newbiggin On Lune, Cumbria, England..
    Eiken, Ola
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Swedish Aerospace Physiology Centre, SAPC.
    Mekjavic, Igor B.
    Jozef Stefan Inst, Dept Automat Biocybernet & Robot, Ljubljana, Slovenia.;Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Burnaby, BC, Canada..
    Indices of Increased Decompression Stress Following Long-Term Bed Rest2018In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 9, article id 442Article in journal (Refereed)
    Abstract [en]

    Human extravehicular activity (EVA) is essential to space exploration and involves risk of decompression sickness (DCS). On Earth, the effect of microgravity on physiological systems is simulated in an experimental model where subjects are confined to a 6 degrees head-down bed rest (HDBR). This model was used to investigate various resting and exercise regimen on the formation of venous gas emboli (VGE), an indicator of decompression stress, post-hyperbaric exposure. Eight healthy male subjects participating in a bed rest regimen also took part in this study, which incorporated five different hyperbaric exposure (HE) interventions made before, during and after the HDBR. Interventions i-iv were all made with the subjects lying in 6 degrees HD position. They included (C1) resting control, (C2) knee-bend exercise immediately prior to HE, (T1) HE during the fifth week of the 35-day HDBR period, (C3) supine cycling exercise during the HE. In intervention (C4), subjects remained upright and ambulatory. The HE protocol followed the Royal Navy Table 11 with 100 min spent at 18 m (280 kPa), with decompression stops at 6 m for 5 min, and at 3 m for 15 min. Post-HE, regular precordial Doppler audio measurements were made to evaluate any VGE produced post-dive. VGE were graded according to the Kisman Masurel scale. The number of bubbles produced was low in comparison to previous studies using this profile [Kisman integrated severity score (KISS) ranging from 0-1], and may be because subjects were young, and lay supine during both the HE and the 2 h measurement period post-HE for interventions i-iv. However, the HE during the end of HDBR produced significantly higher maximum bubble grades and KISS score than the supine control conditions (p < 0.01). In contrast to the protective effect of pre-dive exercise on bubble production, a prolonged period of bed rest prior to a HE appears to promote the formation of post-decompression VGE. This is in contrast to the absence of DCS observed during EVA. Whether this is due to a difference between hypo- and hyperbaric decompression stress, or that the HDBR model is a not a good model for decompression sensitivity during microgravity conditions will have to be elucidated in future studies.

  • 3.
    Groselj, L. Dolenc
    et al.
    Univ Med Ctr, Inst Clin Neurophysiol, Ljubljana, Slovenia..
    Morrison, S.
    Univ Primorska, Fac Hlth, Izola, Slovenia..
    Mirnik, D.
    Univ Med Ctr, Inst Clin Neurophysiol, Ljubljana, Slovenia..
    Korsic, S.
    Univ Med Ctr, Inst Clin Neurophysiol, Ljubljana, Slovenia..
    Eiken, Ola
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology.
    Mekjavic, I.
    Jozef Stefan Inst, Dept Automat Biocybernet & Robot, Ljubljana, Slovenia..
    BED REST AND HYPOXIC EXPOSURE AFFECT SLEEP ARCHITECTURE AND BREATHING STABILITY2017In: Sleep Medicine, ISSN 1389-9457, E-ISSN 1878-5506, Vol. 40, p. E80-E80Article in journal (Other academic)
  • 4.
    Grönkvist, Mikael
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology.
    Levin, Britta
    Eiken, Ola
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology.
    G Tolerance During Open- vs. Closed-Loop G-Time Control.2018In: Aerospace Medicine and Human Performance, ISSN 2375-6314, E-ISSN 2375-6322, Vol. 89, no 9, p. 798-804Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: +Gz tolerance is traditionally determined in centrifuges with open-loop G control, i.e., the centrifuge is under operator control (open loop), and thus the test subject is unable to influence the Gz load. In modern centrifuges, however, the subject is commonly able to continuously control the Gz load (closed loop). It is a widespread opinion among fighter pilots that +Gz tolerance is higher under closed- than open-loop G control. The aims were to investigate whether +Gz tolerance is higher in closed- than open-loop G control, and whether it is possible to use closed-loop G control during precise determination of +Gz tolerance.

    METHODS: Relaxed +Gz tolerance was determined in eight men during rapid Gz-onset rate (ROR) under three conditions: 1) OL-VFB, open loop with visual feedback; 2) OL-NFB, open loop with no visual feedback; and 3) CL, closed loop. Straining +Gz tolerance was determined in 10 men during ROR in OL and CL conditions.

    RESULTS: Relaxed +Gz tolerance did not differ between CL (3.66 Gz), OL-VFB (3.70 Gz) and OL-NFB (3.64 Gz). Straining +Gz tolerance was similar in the CL (8.5 Gz) and OL (8.6 Gz) conditions. In the CL condition, the Gz load varied substantially and was on average lower than in the OL conditions, at any stipulated G-time profile.

    DISCUSSION: There is no systematic difference in relaxed or straining +Gz tolerance as determined in closed- vs. open-loop G-controlled systems. During closed-loop control, precision and reproducibility are too low to recommend it for accurate determination of relaxed G tolerance.Grönkvist M, Levin B, Eiken O. G tolerance during open- vs. closed-loop G-time control. Aerosp Med Hum Perform. 2018; 89(9):798-804.

  • 5.
    Keramidas, Michail E.
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Swedish Aerospace Physiology Centre, SAPC. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology.
    Gadefors, Magnus
    Mil Acad Karlberg, Stockholm, Sweden..
    Nilsson, Lars-Ove
    Mil Acad Karlberg, Stockholm, Sweden..
    Eiken, Ola
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Swedish Aerospace Physiology Centre, SAPC. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology.
    Physiological and psychological determinants of whole-body endurance exercise following short-term sustained operations with partial sleep deprivation2018In: European Journal of Applied Physiology, ISSN 1439-6319, E-ISSN 1439-6327, Vol. 118, no 7, p. 1373-1384Article in journal (Refereed)
    Abstract [en]

    The study examined the effects of short-term field-based military training with partial sleep deprivation on whole-body endurance performance in well-trained individuals. Before and after a 2-day sustained operations (SUSOPS), 14 cadets performed a 15-min constant-load cycling at 65% of peak power output (PPO; CLT65), followed by an exhaustive constant-load trial at 85% of PPO (CLT85). Physiological [oxygen uptake (O-2), heart rate (HR), mean arterial pressure (MAP), cardiac output (CO), and regional oxygenation (TOI) in the frontal cerebral cortex and vastus lateralis muscle] and psychological [effort perception (RPE), affective valence (FS), and perceived activation (FAS)] variables were monitored during exercise. SUSOPS reduced time to exhaustion in CLT85 by 29.1% (p = 0.01). During the CLT65 trial, SUSOPS potentiated the exercise-induced elevations in O-2 and HR (p < 0.05), and blunted MAP (p = 0.001). CO did not differ between trials. Yet, towards the end of both CLT85 trials, CO tended to decline (p 0.08); a response that occurred at an earlier stage in the SUSOPS trial. During CLT65, SUSOPS altered neither cerebral nor muscle TOI. The SUSOPS CLT85 trial, however, was terminated at similar leg-muscle deoxygenation (p > 0.05) and lower prefrontal cortex deoxygenation (p < 0.01). SUSOPS increased RPE at submaximal intensities (p = 0.05), and suppressed FAS and FS throughout (p < 0.01). The present findings indicate, therefore, that a brief period of military sustained operations with partial sleep deprivation augment cardiorespiratory and psychological strain, limiting high-intensity endurance capacity.

  • 6.
    Keramidas, Michail
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Swedish Aerospace Physiology Centre, SAPC.
    Kölegård, Roger
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Swedish Aerospace Physiology Centre, SAPC.
    Eiken, Ola
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Swedish Aerospace Physiology Centre, SAPC.
    In Shackleton’s trails: central and local thermoadaptive modifications to cold and hypoxia after a man-hauling expedition on the Antarctic Plateau2018In: Journal of Thermal Biology, ISSN 0306-4565, E-ISSN 1879-0992, Vol. 73, p. 80-90Article in journal (Refereed)
    Abstract [en]

    Cold and hypoxia constitute the main environmental stressors encountered on the Antarctic Plateau. Hence, we examined whether central and/or peripheral acclimatisation to the combined stressors of cold and hypoxia would be developed in four men following an 11-day man-hauling expedition on this polar region. Before and after the journey, participants performed a static whole-body immersion in 21 degrees C water, during which they were breathing a hypoxic gas (partial pressure of inspired 02: 97 mmHg). To evaluate their local responses to cold, participants also immersed the hand into 8 degrees C water for 30 min, while they were whole-body immersed and mildly hypothermic [i.e. 0.5 degrees C fall in rectal temperature (T-rec) from individual pre-immersion values]. T-rec, and aldn temperature (T-ak), skin blood flux, and oxygen uptake (reflecting shivering thermogenesis) were monitored throughout. The polar expedition accelerated by similar to 14 min the drop in Trr, [final mean (95% confidence interval) changes in T-rec: Before = -0.94 (0.15) degrees C, After: 1.17 (0.23) degrees C]. The shivering onset threshold [Before: 19 (22) min, After: 25 (19) min] and gain [Before: 4.19 (3.95) mL min(-1) kg, After: 1.70 (1.21) mi. min(-1) kg(-1)] were suppressed by the expedition. TA did not differ between trials. The development of a greater post expedition hypothermic state did not compromise finger circulation during the hand-cooling phase. Present findings indicate therefore that a hypothermic pattern of cold acclimatisation, as investigated in hypoxia, was developed following a short-term expedition on the South Polar Plateau; an adaptive response that is characterised mainly by suppressed shivering thermogenesis, and partly by blunted cutaneous vasoconstriction.

  • 7.
    Keramidas, Michail
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology.
    Siebenmann, Christoph
    Norrbrand, Lena
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology.
    Gadefors, Magnus
    Eiken, Ola
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology.
    A brief pre-exercise nap may alleviate physical performance impairments induced by short-term sustained operations with partial sleep deprivation – a field-based study2018In: Chronobiology International, ISSN 0742-0528, E-ISSN 1525-6073Article in journal (Refereed)
  • 8.
    Kölegård, Roger
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology.
    Da Silva, C.
    Siebenmann, Christoph
    KTH.
    Keramidas, Michail E.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Swedish Aerospace Physiology Centre, SAPC.
    Eiken, Ola
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology.
    Cardiac performance is influenced by rotational changes of position in the transversal plane, both in the horizontal and in the 60̊ head-up postures2018In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 38, no 6, p. 1021-1028Article in journal (Refereed)
    Abstract [en]

    Background: Echocardiography is usually performed with the subject/patient lying in the left lateral position (LLP), because the acoustic window is better in this than in the supine position (SP). The aim was to investigate cardiac responses to rotational changes of position in the transversal plane, from SP to LLP while horizontal, and from leaning on the back (HUT-LB) to leaning on the left side (HUT-LL) while tilted 60° head-up from the horizontal. Methods: Healthy men (n = 12) underwent 10-min HUT provocations. Cardiac variables were measured using two-dimensional echocardiography, Doppler, tissue Doppler imaging and arterial pressures using a volume-clamp method. Results: In horizontal posture, cardiac volumes were smaller in SP than in LLP: end-diastolic volume (EDV) by 14%, end-systolic volume (ESV) by 13%, stroke volume (SV) by 14%, and cardiac output (CO) by 16% (P<0·03). In addition, the mitral annular plane systolic excursion (MAPSE) was 11% smaller (P = 0·001) and the left ventricle isovolumic relaxation time (IVRT) 27% longer in SP than in LLP. The ejection fraction, heart rate, arterial pressure and pulmonary ventilation were similar in SP and LLP. During HUT, EDV, SV, CO and MAPSE were smaller, and IVRT was longer, in HUT-LB than in HUT-LL, by −19%, −20%, −17%, −18% and +35%, respectively (P<0·04). Conclusions: Cardiac performance is enhanced in LLP versus SP and in HUT-LL versus HUT-LB, which can be attributed to improved venous return, conceivably, wholly or in part, due to increased hydrostatic pressure gradients between the caval veins and the heart in the LLP and HUT-LL positions.

  • 9.
    Kölegård, Roger
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Swedish Aerospace Physiology Centre, SAPC.
    Da Silva, Cristina
    Department of Physiology, Karolinska University Hospital, Stockholm, Sweden.
    Siebenmann, Christoph
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Swedish Aerospace Physiology Centre, SAPC.
    Keramidas, Michail E.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Swedish Aerospace Physiology Centre, SAPC.
    Eiken, Ola
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Swedish Aerospace Physiology Centre, SAPC.
    Cardiac performance is influenced by rotational changes of position in the transversal plane, both in the horizontal and 60° head-up postures2018In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 38, no 6, p. 1021-1028Article in journal (Refereed)
    Abstract [en]

    Background: Echocardiography is usually performed with the subject/patient lying in the left lateral position (LLP), because the acoustic window is better in this than in the supine position (SP). The aim was to investigate cardiac responses to rotational changes of position in the transversal plane, from SP to LLP while horizontal, and from leaning on the back (HUT-LB) to leaning on the left side (HUT-LL) while tilted 60° head-up from the horizontal. Methods: Healthy men (n = 12) underwent 10-min HUT provocations. Cardiac variables were measured using two-dimensional echocardiography, Doppler, tissue Doppler imaging and arterial pressures using a volume-clamp method. Results: In horizontal posture, cardiac volumes were smaller in SP than in LLP: end-diastolic volume (EDV) by 14%, end-systolic volume (ESV) by 13%, stroke volume (SV) by 14%, and cardiac output (CO) by 16% (P<0·03). In addition, the mitral annular plane systolic excursion (MAPSE) was 11% smaller (P = 0·001) and the left ventricle isovolumic relaxation time (IVRT) 27% longer in SP than in LLP. The ejection fraction, heart rate, arterial pressure and pulmonary ventilation were similar in SP and LLP. During HUT, EDV, SV, CO and MAPSE were smaller, and IVRT was longer, in HUT-LB than in HUT-LL, by −19%, −20%, −17%, −18% and +35%, respectively (P<0·04). Conclusions: Cardiac performance is enhanced in LLP versus SP and in HUT-LL versus HUT-LB, which can be attributed to improved venous return, conceivably, wholly or in part, due to increased hydrostatic pressure gradients between the caval veins and the heart in the LLP and HUT-LL positions.

  • 10.
    Kölegård, Roger
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology.
    Da Silva, Cristina
    Siebenmann, Christoph
    Keramidas, Michail E.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Swedish Aerospace Physiology Centre, SAPC.
    Eiken, Ola
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology.
    Hjärtats minutvolym vid olika kroppspositioner2018Conference paper (Refereed)
  • 11. Rullman, Eric
    et al.
    Fernandez-Gonzalo, Rodrigo
    Mekjavić, Igor B.
    Gustafsson, Thomas
    Eiken, Ola
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology.
    Mef2 as upstream regulator of the transcriptome signature in human skeletal muscle during unloading2018In: American Journal of Physiology. Regulatory Integrative and Comparative Physiology, ISSN 0363-6119, E-ISSN 1522-1490Article in journal (Refereed)
    Abstract [en]

    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 m. vastus lateralis biopsies obtained from 12 men before and after the bed rest were analyzed using a microarray. There were 54 significantly up-regulated probesets after bed rest, whereas 103 probesets were down-regulated (FDR 10%; fold-change cut-off ≥1.5). Amongst the up-regulated genes, transcripts related to denervation-induced alterations in skeletal muscle were identified, e.g. CHRND and perinatal myosin. The most down-regulated 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 MEF2 family, in particular MEF2C, which was suggested to act upstream of several key down-regulated genes, most notably PGC-1α/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.

  • 12.
    Salvadego, Desy
    et al.
    Univ Udine, Dept Med, Piazzale M Kolbe 4, I-33100 Udine, Italy..
    Keramidas, Michail E.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Swedish Aerospace Physiology Centre, SAPC.
    Kölegård, Roger
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Swedish Aerospace Physiology Centre, SAPC.
    Brocca, Lorenza
    Univ Pavia, Dept Mol Med, Pavia, Italy..
    Lazzer, Stefano
    Univ Udine, Dept Med, Piazzale M Kolbe 4, I-33100 Udine, Italy..
    Mavelli, Irene
    Univ Udine, Dept Med, Piazzale M Kolbe 4, I-33100 Udine, Italy..
    Rittweger, Joern
    German Aerosp Ctr, Inst Aerosp Med, Cologne, Germany.;Univ Cologne, Fac Med, Dept Pediat & Adolescent Med, Cologne, Germany..
    Eiken, Ola
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Swedish Aerospace Physiology Centre, SAPC.
    Mekjavic, Igor B.
    Jozef Stefan Inst, Dept Automat Biocybernet & Robot, Ljubljana, Slovenia.;Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Burnaby, BC, Canada..
    Grassi, Bruno
    Univ Udine, Dept Med, Piazzale M Kolbe 4, I-33100 Udine, Italy.;CNR, Inst Bioimaging & Mol Physiol, Milan, Italy..
    PlanHab(*): hypoxia does not worsen the impairment of skeletal muscle oxidative function induced by bed rest alone2018In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 596, no 15, p. 3341-3355Article in journal (Refereed)
    Abstract [en]

    Skeletal muscle oxidative function was evaluated in 11 healthy males (mean +/- SD age 27 +/- 5years) prior to (baseline data collection, BDC) and following a 21day horizontal bed rest (BR), carried out in normoxia (P-IO2=133 mmHg; N-BR) and hypoxia (P-IO2=90 mmHg; H-BR). H-BR was aimed at simulating reduced gravity habitats. The effects of a 21day hypoxic ambulatory confinement (P-IO2=90 mmHg; H-AMB) were also assessed. Pulmonary O-2 uptake (<(V) over dot>O-2), vastus lateralis fractional O-2 extraction (changes in deoxygenated haemoglobin+myoglobin concentration, Delta[deoxy(Hb+Mb)]; near-infrared spectroscopy) and femoral artery blood flow (ultrasound Doppler) were evaluated during incremental one-leg knee-extension exercise (reduced constraints to cardiovascular O-2 delivery) carried out to voluntary exhaustion in a normoxic environment. Mitochondrial respiration was evaluated ex vivo by high-resolution respirometry in permeabilized vastus lateralis fibres. <(V) over dot>(O2peak) decreased (P<0.05) after N-BR (0.98 +/- 0.13 L min(-1)) and H-BR (0.96 +/- 0.17 L min(-1)) vs. BDC (1.05 +/- 0.14 L min(-1)). In the presence of a decreased (by similar to 6-8%) thigh muscle volume, <(V) over dot>(O2peak) normalized per unit of muscle mass was not affected by both interventions. Delta[deoxy(Hb+Mb)](peak) decreased (P<0.05) after N-BR (65 +/- 13% of limb ischaemia) and H-BR (62 +/- 12%) vs. BDC (73 +/- 13%). H-AMB did not alter <(V) over dot>(O2peak) or Delta[deoxy(Hb+Mb)](peak). An overshoot of Delta[deoxy(Hb+Mb)] was evident during the first minute of unloaded exercise after N-BR and H-BR. Arterial blood flow to the lower limb during both unloaded and peak knee extension was not affected by any intervention. Maximal ADP-stimulated mitochondrial respiration decreased (P<0.05) after all interventions vs. control. In 21day N-BR, a significant impairment of oxidative metabolism occurred downstream of cardiovascular O-2 delivery, affecting both mitochondrial respiration and presumably the intramuscular matching between O-2 supply and utilization. Superposition of H on BR did not worsen the impairment induced by BR alone.

  • 13. Sotiridis, Alexandros
    et al.
    Debevec, Tadej
    McDonnell, Adam C.
    Ciuha, Ursa
    Eiken, Ola
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology.
    Mekjavic, Igor B
    Exercise cardiorespiratory and thermoregulatory responses in normoxic, hypoxic and hot environment following 10-day continuous hypoxic exposure.2018In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601Article in journal (Refereed)
    Abstract [en]

    We examined the effects of acclimatization to normobaric hypoxia on aerobic performance and exercise thermoregulatory responses under normoxic, hypoxic and hot conditions. Twelve males performed tests of maximal oxygen uptake (V̇O2max) in normoxic (NOR), hypoxic (13.5% FiO2; HYP) and hot (35℃, 50% RH; HE) conditions in a randomized manner before and after a 10-day continuous normobaric hypoxic exposure (FiO2 = 13.65(0.35)%, PiO2 = 87(3) mmHg). The acclimatization protocol included daily exercise (60min @ 50% hypoxia-specific peak power output, Wpeak). All maximal tests were preceded by a steady-state exercise (30 min at 40% Wpeak) to assess the sweating response. Hematological data were assessed from venous blood samples obtained before and after acclimatization. V̇O2max increased by 10.7% (P = 0.002) and 7.9% (P = 0.03) from pre- to post-acclimatization in NOR and HE, respectively, whereas no differences were found in HYP (pre: 39.9(3.8) vs post: 39.4(5.1) mL.kg-1.min-1, P = 1.0). However, the increase in V̇O2max did not translate into increased Wpeak in either NOR or HE. Maximal heart rate and ventilation remained unchanged following acclimatization. Νo differences were noted in the sweating gain and thresholds independent of the acclimatization or environmental conditions. Hypoxic acclimatization markedly increased hemoglobin (P &lt; 0.001), hematocrit (P &lt; 0.001) and extracellular HSP72 (P = 0.01). These data suggest that 10 days of normobaric hypoxic acclimatization combined with moderate-intensity exercise training improves V̇O2max in NOR and HE, but does not seem to affect exercise performance or thermoregulatory responses in any of the tested environmental conditions.

  • 14. Stavrou, N. A. M.
    et al.
    Debevec, T.
    Eiken, Ola
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology.
    Mekjavic, I. B.
    Hypoxia worsens affective responses and feeling of fatigue during prolonged bed rest2018In: Frontiers in Psychology, ISSN 1664-1078, E-ISSN 1664-1078, Vol. 9, no MAR, article id 362Article in journal (Refereed)
    Abstract [en]

    Previous research, although limited, suggests that both hypoxia and bed rest influence psychological responses by exaggerating negative psychological responses and attenuating positive emotions. The present study investigated the effect of a 21-day prolonged exposure to normobaric hypoxia and bed rest on affective responses and fatigue. Eleven healthy participants underwent three 21-day interventions using a cross-over design: (1) normobaric hypoxic ambulatory confinement (HAMB), (2) normobaric hypoxic bed rest (HBR) and (3) normoxic bed rest (NBR). Affective and fatigue responses were investigated using the Activation Deactivation Adjective Check List, and the Multidimensional Fatigue Inventory, which were completed before (Pre), during (Day 7, Day 14, and Day 21) and after (Post) the interventions. The most negative psychological profile appeared during the HBR intervention. Specifically, tiredness, tension, general and physical fatigue significantly increased on days 7, 14, and 21, as well as at Post. After the HBR intervention, general and physical fatigue remained higher compared to Pre values. Additionally, a deterioration of psychological responses was also noted following HAMB and NBR. In particular, both hypoxia and BR per se induced subjective fatigue and negative affective responses. BR seems to exert a moderate negative effect on the sensation of fatigue, whereas exercise attenuates the negative effects of hypoxia as noted during the HAMB condition. In conclusion, our data suggest that the addition of hypoxia to bed rest-induced inactivity significantly worsens affective responses and feeling of fatigue.

  • 15. Stavrou, Nektarios A. M.
    et al.
    Debevec, Tadej
    Eiken, Ola
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Swedish Aerospace Physiology Centre, SAPC.
    Mekjavic, Igor B.
    Hypoxia Exacerbates Negative Emotional State during Inactivity: The Effect of 21 Days Hypoxic Bed Rest and Confinement2018In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 9, article id 26Article in journal (Refereed)
    Abstract [en]

    Hypoxia and confinement have both been shown to influence emotional state. It is envisaged that the inhabitants of future planetary habitats will be exposed to concomitant confinement, reduced gravity and hypoxia. We examined the independent and combined effects of a 21-day inactivity/unloading and normobaric hypoxia under confined conditions on various psychological factors. Eleven healthy men participated in three 21-day experimental campaigns designed in a cross-over manner (1) Normobaric hypoxic ambulatory confinement, (2) Normobaric hypoxic bed rest and (3) Normobaric normoxic bed rest. The Profile of Mood States, and the Positive and Negative Affect Schedule were employed to assess the participants' psychological responses before (Pre), during (Day 7, Day 14, and Day 21) and after (Post) the confinements. The most negative psychological profile appeared on days 14 and 21 of the hypoxic bed rest campaign. A significant increase in depression, tension, and confusion was noted on days 14 and 21 of the hypoxic bed rest condition. Concomitantly, a decrease, albeit not statistically significant, in positive psychological responses was observed. The psychological profile returned to the initial level at Post following all confinements. These data suggest that the combined effect of hypoxia and bed rest induced the most negative effects on an individual's mood. However, significant intra- and inter-individual differences in psychological responses were noted and should be taken into consideration.

  • 16. Strewe, C.
    et al.
    Zeller, R.
    Feuerecker, M.
    Hoerl, M.
    Matzel, S.
    Kumprej, I.
    Crispin, A.
    Johannes, B.
    Debevec, T.
    Mekjavic, I. B.
    Eiken, Ola
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Swedish Aerospace Physiology Centre, SAPC.
    Thiel, M.
    Schelling, G.
    Choukèr, A.
    PlanHab Study: Consequences of combined normobaric hypoxia and bed rest on adenosine kinetics2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, no 1, article id 1762Article in journal (Refereed)
    Abstract [en]

    Adenosine plays a role in the energy supply of cells and provokes differential, hormone-like functions in circulating cells and various tissues. Its release is importantly regulated by oxygen tension. This renders adenosine and its kinetics interesting to investigate in humans subjected to low oxygen conditions. Especially for space exploration scenarios, hypoxic conditions - together with reduced gravity - represent two foreseen living conditions when planning manned long-duration space missions or planetary habitats. The PlanHab study investigated microgravity through inactivity in bed rest and normobaric hypoxia to examine their independent or combined effect on adenosine and its kinetics. Healthy male subjects (n = 14) completed three 21-day interventions: hypoxic bed rest (HBR); hypoxic ambulatory confinement (HAMB); normoxic bed rest (NBR). The interventions were separated by 4 months. Our hypothesis of a hypoxia-triggered increase in adenosine was confirmed in HAMB but unexpectedly also in NBR. However, the highest adenosine levels were noted following HBR. Furthermore, the percentage of hemolysis was elevated in HBR whereas endothelial integrity markers stayed low in all three interventions. In summary, these data suggest that neocytolysis accounts for these effects while we could reduce evidence for microcirculatory changes.

  • 17.
    Sundblad, Patrik
    et al.
    Karolinska Inst, Dept Lab Med, Clin Physiol, SE-14186 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Clin Physiol, SE-14186 Stockholm, Sweden..
    Kölegård, Roger
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology.
    Rullman, Eric
    Karolinska Inst, Dept Lab Med, Clin Physiol, SE-14186 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Clin Physiol, SE-14186 Stockholm, Sweden..
    Gustafsson, Thomas
    Karolinska Inst, Dept Lab Med, Clin Physiol, SE-14186 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Clin Physiol, SE-14186 Stockholm, Sweden..
    Effects of training with flow restriction on the exercise pressor reflex2018In: European Journal of Applied Physiology, ISSN 1439-6319, E-ISSN 1439-6327, Vol. 118, no 9, p. 1903-1909Article in journal (Refereed)
    Abstract [en]

    We hypothesized that 5 weeks of endurance training with blood flow restriction (R-training), providing relative ischemia and stimulation of the muscle chemoreflex, would decrease the exercise pressor reflex (EPR) when compared to training with the same workload in a free-flow condition (NR-training). 10 subjects performed one-leg knee-extension training four times a week during a 5-week period. Both legs were trained with identical workload, with one leg being trained during flow-restriction induced by lower body positive pressure. The EPR was assessed by measuring the increase in heart rate (HR) and mean arterial pressure (MAP) during an isometric knee extension of 35% of max torque for 90 s, this was done before (C), and after training in each leg (R and NR, respectively). At the end of isometric contraction, the increase in mean AP (MAP) in the NR-trained leg and in the control condition were 41 +/- 4 and 38 +/- 4 mmHg, respectively, whereas the increase in the R-trained leg was 30 +/- 4 mmHg (p < 0.05 R vs C and NR), corresponding to a decrease of about 25%. A similar patter was observed with respect to responses in HR, where the increase was 28 +/- 3 and 28 +/- 3 bpm in the NR and C, and 22 +/- 4 in the R condition (p < 0.05 R vs C and NR). Peripheral metabolic changes induced by relative ischemia are important in modifying the EPR in response to exercise training.

  • 18. Šarabon, N.
    et al.
    Mekjavić, I. B.
    Eiken, Ola
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Swedish Aerospace Physiology Centre, SAPC.
    Babič, J.
    The effect of bed rest and hypoxic environment on postural balance and trunk automatic (re)actions in young healthy males2018In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 9, no January, article id 27Article in journal (Refereed)
    Abstract [en]

    Prolonged inactivity, such as bed rest induces several detrimental changes within a short timeframe. Impaired postural balance and responses of trunk muscles to (un)expected perturbations were both shown to be impaired after bed rest. Certain populations (e.g., astronauts) are exposed to hypoxic environment in addition to inactivity, similar to bed rest. While the isolated negative effects of hypoxia on postural balance have been observed before, no study to date has examined the combined effects of hypoxia and bed rest on postural balance or trunk muscle responses. In this study, we examined the effects of 21-day exposure to three conditions: (i) bed rest in hypoxic environment (HBR), (ii) bed rest in normoxic environment (NBR), and (iii) ambulatory hypoxic environment (HAMB). Fourteen healthy male subjects crossed over between conditions in a randomized order, with a 4-month break between conditions to ensure full recovery. Most body sway parameters indicated a similar deterioration of postural balance following both HBR and NBR. Similarly, both anticipatory and reactive responses of the trunk muscles (m. erector spinae and m. multifidus) were impaired after HBR and NBR to a similar degree and mostly unchanged after HAMB. Certain body sway parameters were impaired after HAMB, confirming that hypoxia alone can undermine postural balance. On the other hand, some trunk responses were improved after HAMB. In conclusion, the results of our study confirmed previous findings on negative effects of bed rest, but showed little or no additional effect of hypoxia during bed rest. Physical activity during bed rest is encouraged to preserve neuromuscular functions of the trunk. While the HBR condition in our study resembled conditions during space missions, our results could be relevant to other populations, such as patients with pulmonary diseases exposed to bed rest.

  • 19. Šket, R.
    et al.
    Debevec, T.
    Kublik, S.
    Schloter, M.
    Schoeller, A.
    Murovec, B.
    Mikuš, K. V.
    Makuc, D.
    Pečnik, K.
    Plavec, J.
    Mekjavić, I. B.
    Eiken, Ola
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Swedish Aerospace Physiology Centre, SAPC.
    Prevoršek, Z.
    Stres, B.
    Intestinal metagenomes and metabolomes in healthy young males: Inactivity and hypoxia generated negative physiological symptoms precede microbial dysbiosis2018In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 9, no Mars, article id 198Article in journal (Refereed)
    Abstract [en]

    We explored the metagenomic, metabolomic and trace metal makeup of intestinal microbiota and environment in healthy male participants during the run-in (5 day) and the following three 21-day interventions: normoxic bedrest (NBR), hypoxic bedrest (HBR) and hypoxic ambulation (HAmb) which were carried out within a controlled laboratory environment (circadian rhythm, fluid and dietary intakes, microbial bioburden, oxygen level, exercise). The fraction of inspired O2 (FiO2) and partial pressure of inspiredO2 (PiO2) were 0.209 and 133.1 ± 0.3 mmHg for the NBR and 0.141 ± 0.004 and 90.0 ± 0.4 mmHg (~4,000 m simulated altitude) for HBR and HAmb interventions, respectively. Shotgun metagenomes were analyzed at various taxonomic and functional levels, 1H-and 13C-metabolomes were processed using standard quantitative and human expert approaches, whereas metals were assessed using X-ray fluorescence spectrometry. Inactivity and hypoxia resulted in a significant increase in the genus Bacteroides in HBR, in genes coding for proteins involved in iron acquisition and metabolism, cell wall, capsule, virulence, defense and mucin degradation, such as beta-galactosidase (EC3.2.1.23), α-L-fucosidase (EC3.2.1.51), Sialidase (EC3.2.1.18), and α-N-acetylglucosaminidase (EC3.2.1.50). In contrast, the microbial metabolomes, intestinal element and metal profiles, the diversity of bacterial, archaeal and fungal microbial communities were not significantly affected. The observed progressive decrease in defecation frequency and concomitant increase in the electrical conductivity (EC) preceded or took place in absence of significant changes at the taxonomic, functional gene, metabolome and intestinal metal profile levels. The fact that the genus Bacteroides and proteins involved in iron acquisition and metabolism, cell wall, capsule, virulence and mucin degradation were enriched at the end of HBR suggest that both constipation and EC decreased intestinal metal availability leading to modified expression of co-regulated genes in Bacteroides genomes. Bayesian network analysis was used to derive the first hierarchical model of initial inactivity mediated deconditioning steps over time. The PlanHab wash-out period corresponded to a profound life-style change (i.e., reintroduction of exercise) that resulted in stepwise amelioration of the negative physiological symptoms, indicating that exercise apparently prevented the crosstalk between the microbial physiology, mucin degradation and proinflammatory immune activities in the host.

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