| 1. |
- Marshall-Goebel, Karina, et al.
(författare)
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Effects of short-term exposure to head-down tilt on cerebral hemodynamics : a prospective evaluation of a spaceflight analog using phase-contrast MRI
- 2016
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Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 120:12, s. 1466-1473
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Tidskriftsartikel (refereegranskat)abstract
- Alterations in cerebral hemodynamics in microgravity are hypothesized to occur during spaceflight and could be linked to the Visual Impairment and Intracranial Pressure syndrome. Head-down tilt (HDT) is frequently used as a ground-based analog to simulate cephalad fluid shifts in microgravity; however, its effects on cerebral hemodynamics have not been well studied with MRI techniques. Here, we evaluate the effects of 1) various HDT angles on cerebral arterial and venous hemodynamics; and 2) exposure to 1% CO2 during an intermediate HDT angle (-12 degrees) as an additional space-related environmental factor. Blood flow, cross-sectional area (CSA), and blood flow velocity were measured with phase-contrast MRI in the internal jugular veins, as well as the vertebral and internal carotid arteries. Nine healthy male subjects were measured at baseline (supine, 0 degrees) and after 4.5 h of HDT at -6 degrees, -12 degrees (with and without 1% CO2), and -18 degrees. We found a decrease in total arterial blood flow from baseline during all angles of HDT. On the venous side, CSA increased with HDT, and outflow decreased during -12 degrees HDT (P = 0.039). Moreover, the addition of 1% CO2 to -12 degrees HDT caused an increase in total arterial blood flow (P = 0.016) and jugular venous outflow (P = 0.001) compared with -12 degrees HDT with ambient atmosphere. Overall, the results indicate decreased cerebral blood flow during HDT, which may have implications for microgravity-induced cerebral hemodynamic changes.
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| 2. |
- McDonnell, Adam C., et al.
(författare)
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The LunHab project : Muscle and bone alterations in male participants following a 10 day lunar habitat simulation.
- 2019
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Ingår i: Experimental Physiology. - : Wiley. - 0958-0670 .- 1469-445X. ; 104:8, s. 1250-1261
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Tidskriftsartikel (refereegranskat)abstract
- NEW FINDINGS: What is the central question of this study? It is well established that muscle and bone atrophy in conditions of inactivity or unloading, but there is little information regarding the effect of a hypoxic environment on the time course of these deconditioning physiological systems. What is the main finding and its importance? The main finding is that a horizontal 10 day bed rest in normoxia results in typical muscle atrophy, which is not aggravated by hypoxia. Changes in bone mineral content or in metabolism were not detected after either normoxic or hypoxic bed rest.ABSTRACT: Musculoskeletal atrophy constitutes a typical adaptation to inactivity and unloading of weightbearing bones. The reduced-gravity environment in future Moon and Mars habitats is likely to be hypobaric hypoxic, and there is an urgent need to understand the effect of hypoxia on the process of inactivity-induced musculoskeletal atrophy. This was the principal aim of the present study. Eleven males participated in three 10 day interventions: (i) hypoxic ambulatory confinement; (ii) hypoxic bed rest; and (iii) normoxic bed rest. Before and after the interventions, the muscle strength (isometric maximal voluntary contraction), mass (lean mass, by dual-energy X-ray absorptiometry), cross-sectional area and total bone mineral content (determined with peripheral quantitative computed tomography) of the participants were measured. Blood and urine samples were collected before and on the 1st, 4th and 10th day of the intervention and analysed for biomarkers of bone resorption and formation. There was a significant reduction in thigh and lower leg muscle mass and volume after both normoxic and hypoxic bed rests. Muscle strength loss was proportionately greater than the loss in muscle mass for both thigh and lower leg. There was no indication of bone loss. Furthermore, the biomarkers of resorption and formation were not affected by any of the interventions. There was no significant effect of hypoxia on the musculoskeletal variables. Short-term normoxic (10 day) bed rest resulted in muscular deconditioning, but not in the loss of bone mineral content or changes in bone metabolism. Hypoxia did not modify these results.
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| 3. |
- Rittweger, Joern, et al.
(författare)
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On the combined effects of normobaric hypoxia and bed rest upon bone and mineral metabolism : Results from the PlanHab study
- 2016
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Ingår i: Bone. - : Elsevier. - 8756-3282 .- 1873-2763. ; 91, s. 130-138
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Tidskriftsartikel (refereegranskat)abstract
- Bone losses are common as a consequence of unloading and also in patients with chronic obstructive pulmonary disease (COPD). Although hypoxia has been implicated as an important factor to drive bone loss, its interaction with unloading remains unresolved. The objective therefore was to assess whether human bone loss caused by unloading could be aggravated by chronic hypoxia. In a cross-over designed study, 14 healthy young men underwent 21-day interventions of bed rest in normoxia (NBR), bed rest in hypoxia (HBR), and hypoxic ambulatory confinement (HAmb). Hypoxic conditions were equivalent to 4000 m altitude. Bone metabolism (NTX, P1NP, sclerostin, DKK1) and phospho-calcic homeostasis (calcium and phosphate serum levels and urinary excretion, PTH) were assessed from regular blood samples and 24-hour urine collections, and tibia and femur bone mineral content was assessed by peripheral quantitative computed tomography (pQCT). Urinary NTX excretion increased (P<0.001) to a similar extent in NBR and HBR (P = 0.69) and P1NP serum levels decreased (P = 0.0035) with likewise no difference between NBR and HBR (P = 0.88). Serum total calcium was increased during bed rest by 0.059 (day D05, SE 0.05 mM) to 0.091 mM (day D21, P < 0.001), with no additional effect by hypoxia during bed rest (P = 0.199). HAmb led, at least temporally, to increased total serum calcium, to reduced serum phosphate, and to reduced phosphate and calcium excretion. In conclusion, hypoxia did not aggravate bed rest-induced bone resorption, but led to changes in phospho-calcic homeostasis likely caused by hyperventilation. Whether hyperventilation could have mitigated the effects of hypoxia in this study remains to be established.
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| 4. |
- Rittweger, Joern, et al.
(författare)
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Short-arm centrifugation as a partially effective musculoskeletal countermeasure during 5-day head-down tilt bed rest-results from the BRAG1 study
- 2015
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Ingår i: European Journal of Applied Physiology. - : Springer Science and Business Media LLC. - 1439-6319 .- 1439-6327. ; 115:6, s. 1233-1244
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Tidskriftsartikel (refereegranskat)abstract
- Human centrifugation, also called artificial gravity (AG), is proposed as a combined strategy against detrimental effects of microgravity in long-term space missions. This study scrutinized human short-arm centrifugation as countermeasure against musculoskeletal de-conditioning. Eleven healthy male subjects [mean age of 34 (SD 7) years] completed the cross-over trial, including three campaigns of -6A degrees head-down tilt bed rest (HDT) for 5 days, with preceding baseline data collection and recovery phases. Bed rest without AG was used as control condition (Ctrl), and AG with 1 g at the center of mass applied once per day for 30 min in one bout (AG(1x30)) and in 6 bouts of 5 min (AG(6x5), 3-min rest between bouts) as experimental conditions. End-points were muscle strength, vertical jump performance, and biomarkers of bone and protein metabolism. AG(6x5) was better tolerated than AG(1x30). Bone resorption markers CTX, NTX, and DPD all increased by approximately 25 % toward the end of bed rest (P < 0.001), and nitrogen balance decreased by approximately 3 g/day (P < 0.001), without any protection by AG (P > 0.4). Decreases in vertical jump height by 2.1 (SE 0.6) cm after Ctrl bed rest was prevented by either of the AG protocols (P = 0.039). The present study yielded succinct catabolic effects upon muscle and bone metabolism that were un-prevented by AG. The preservation of vertical jump performance by AG in this study is likely caused by central nervous rather than by peripheral musculoskeletal effects.
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| 5. |
- Salvadego, Desy, et al.
(författare)
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PlanHab(*) : hypoxia does not worsen the impairment of skeletal muscle oxidative function induced by bed rest alone
- 2018
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Ingår i: Journal of Physiology. - : Wiley. - 0022-3751 .- 1469-7793. ; 596:15, s. 3341-3355
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 6. |
- Šket, Robert, et al.
(författare)
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Systems View of Deconditioning During Spaceflight Simulation in the PlanHab Project : The Departure of Urine 1 H-NMR Metabolomes From Healthy State in Young Males Subjected to Bedrest Inactivity and Hypoxia.
- 2020
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Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- We explored the metabolic makeup of urine in prescreened healthy male participants within the PlanHab experiment. The run-in (5 day) and the following three 21-day interventions [normoxic bedrest (NBR), hypoxic bedrest (HBR), and hypoxic ambulation (HAmb)] were executed in a crossover manner within a controlled laboratory setup (medical oversight, fluid and dietary intakes, microbial bioburden, circadian rhythm, and oxygen level). The inspired O2 (FiO2) fraction next to inspired O2 (PiO2) partial pressure were 0.209 and 133.1 ± 0.3 mmHg for the NBR variant in contrast to 0.141 ± 0.004 and 90.0 ± 0.4 mmHg (approx. 4,000 m of simulated altitude) for HBR and HAmb interventions, respectively. 1H-NMR metabolomes were processed using standard quantitative approaches. A consensus of ensemble of multivariate analyses showed that the metabolic makeup at the start of the experiment and at HAmb endpoint differed significantly from the NBR and HBR endpoints. Inactivity alone or combined with hypoxia resulted in a significant reduction of metabolic diversity and increasing number of affected metabolic pathways. Sliding window analysis (3 + 1) unraveled that metabolic changes in the NBR lagged behind those observed in the HBR. These results show that the negative effects of cessation of activity on systemic metabolism are further aggravated by additional hypoxia. The PlanHab HAmb variant that enabled ambulation, maintained vertical posture, and controlled but limited activity levels apparently prevented the development of negative physiological symptoms such as insulin resistance, low-level systemic inflammation, constipation, and depression. This indicates that exercise apparently prevented the negative spiral between the host's metabolism, intestinal environment, microbiome physiology, and proinflammatory immune activities in the host.
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