Acute cardiovascular and muscular response to rowing ergometer exercise in artificial gravity - a pilot trial.

Prolonged immobilization and spaceflight cause cardiovascular and musculoskeletal deconditioning. Combining artificial gravity through short-arm centrifugation with rowing exercise may serve as a countermeasure. We aimed to compare the tolerability, muscle force production, cardiovascular response, and power output of rowing on a short-arm centrifuge and under terrestrial gravity. Twelve rowing athletes (4 women, aged 27.2 ± 7.4 years, height 179 ± 0.1 cm, mass 73.7 ± 9.4 kg) participated in two rowing sessions, spaced at least six weeks apart. One session used a short-arm centrifuge with +0.5 Gz, while the other inclined the rowing ergometer by 26.6° to mimic centrifugal loading. Participants started self-paced rowing at 30 W, increasing by 15 W every three minutes until exhaustion. We measured rowing performance, heart rate, blood pressure, ground reaction forces, leg muscle activation, and blood lactate concentration. Rowing on the centrifuge was well-tolerated without adverse events. No significant differences in heart rate, blood pressure, or blood lactate concentration were observed between conditions. Inclined rowing under artificial gravity resulted in lower power output (-33%, p < 0.001) compared to natural gravity, but produced higher mean and peak ground reaction forces (p < 0.0001) and increased leg muscle activation. Muscle activation and ground reaction forces varied with rotational direction. Rowing in artificial gravity shows promise as a strategy against cardiovascular and muscular deconditioning during long-term spaceflight, but further investigation is required to understand its long-term effects.

Assessing the effects of artificial gravity in an analog of long-duration spaceflight: The protocol and implementation of the AGBRESA bed rest study.

A comprehensive strategy is required to mitigate risks to astronauts' health, well-being, and performance. This strategy includes developing countermeasures to prevent or reduce adverse responses to the stressors astronauts encounter during spaceflight, such as weightlessness. Because artificial gravity (AG) by centrifugation simultaneously affects all physiological systems, AG could mitigate the effects of weightlessness in multiple systems. In 2019, NASA and the German Aerospace Center conducted a 60-days Artificial Gravity Bed Rest Study with the European Space Agency (AGBRESA). The objectives of this study were to 1) determine if 30 min of AG daily is protective during head down bed rest, and 2) compare the protective effects of a single daily bout (30 min) of AG versus multiple daily bouts (6 × 5 min) of AG (1 Gz at the center of mass) on physiological functions that are affected by weightlessness and by head-down tilt bed rest. The AGBRESA study involved a comprehensive suite of standard and innovative technologies to characterize changes in a broad spectrum of physiological systems. The current article is intended to provide a detailed overview of the methods used during AGBRESA.

Comparison of trunk muscle exercises in supine position during short arm centrifugation with 1 g at centre of mass and upright in 1 g.

Spaceflight is associated with reduced antigravitational muscle activity, which results in trunk muscle atrophy and may contribute to post-flight postural and spinal instability. Exercise in artificial gravity (AG) performed via short-arm human centrifugation (SAHC) is a promising multi-organ countermeasure, especially to mitigate microgravity-induced postural muscle atrophy. Here, we compared trunk muscular activity (mm. rectus abdominis, ext. obliques and multifidi), cardiovascular response and tolerability of trunk muscle exercises performed during centrifugation with 1 g at individual center of mass on a SAHC against standard upright exercising. We recorded heart rate, blood pressure, surface trunk muscle activity, motion sickness and rating of perceived exertion (BORG) of 12 participants (8 male/4 female, 34 ± 7 years, 178.4 ± 8.2 cm, 72.1 ± 9.6 kg). Heart rate was significantly increased (p < 0.001) during exercises without differences in conditions. Systolic blood pressure was higher (p < 0.001) during centrifugation with a delayed rise during exercises in upright condition. Diastolic blood pressure was lower in upright (p = 0.018) compared to counter-clockwise but not to clockwise centrifugation. Target muscle activation were comparable between conditions, although activity of multifidi was lower (clockwise: p = 0.003, counter-clockwise: p < 0.001) and rectus abdominis were higher (clockwise: p = 0.0023, counter-clockwise: < 0.001) during centrifugation in one exercise type. No sessions were terminated, BORG scoring reflected a relevant training intensity and no significant increase in motion sickness was reported during centrifugation. Thus, exercising trunk muscles during centrifugation generates comparable targeted muscular and heart rate response and appears to be well tolerated. Differences in blood pressure were relatively minor and not indicative of haemodynamic challenge. SAHC-based muscle training is a candidate to reduce microgravity-induced inter-vertebral disc pathology and trunk muscle atrophy. However, further optimization is required prior to performance of a training study for individuals with trunk muscle atrophy/dysfunction.

Hypergravity Attenuates Reactivity in Primary Murine Astrocytes.

Neuronal activity is the key modulator of nearly every aspect of behavior, affecting cognition, learning, and memory as well as motion. Hence, disturbances of the transmission of synaptic signals are the main cause of many neurological disorders. Lesions to nervous tissues are associated with phenotypic changes mediated by astrocytes becoming reactive. Reactive astrocytes form the basis of astrogliosis and glial scar formation. Astrocyte reactivity is often targeted to inhibit axon dystrophy and thus promote neuronal regeneration. Here, we aim to understand the impact of gravitational loading induced by hypergravity to potentially modify key features of astrocyte reactivity. We exposed primary murine astrocytes as a model system closely resembling the in vivo reactivity phenotype on custom-built centrifuges for cultivation as well as for live-cell imaging under hypergravity conditions in a physiological range (2g and 10g). We revealed spreading rates, migration velocities, and stellation to be diminished under 2g hypergravity. In contrast, proliferation and apoptosis rates were not affected. In particular, hypergravity attenuated reactivity induction. We observed cytoskeletal remodeling of actin filaments and microtubules under hypergravity. Hence, the reorganization of these key elements of cell structure demonstrates that fundamental mechanisms on shape and mobility of astrocytes are affected due to altered gravity conditions. In future experiments, potential target molecules for pharmacological interventions that attenuate astrocytic reactivity will be investigated. The ultimate goal is to enhance neuronal regeneration for novel therapeutic approaches.

Quantitative Evaluation of a Telerobotic System for Vascular Ultrasound Measurement on a Short Arm Human Centrifuge.

Artificial Gravity generated by Short Arm Human Centrifuges is a promising multi-system countermeasure for physiological deconditioning during long duration space flights. To allow a continuous assessment of cardiovascular hemodynamics during centrifugation, a telerobotic robotic system holding an ultrasound probe has been installed on a Short Arm Human Centrifuge. A feasibility study was conducted to define the use capabilities and limitations of such a novel method. The objective of this study is to estimate the reproducibility and precision of remotely controlled vascular ultrasound assessment under centrifugation by assessing peripheral vascular diameter and wall distension. Four repeated centrifugation runs of 5 min, with 2.4 g at feet level, were performed including a 15 min rest between each run for a group of eight healthy male volunteers. Vascular diameter and distention were assessed for the common carotid artery (CCA) and the femoral artery (FA) by ultrasound imaging using a 10 MHz linear array probe (Mylab1, Esaote). Ultrasound measurements were consecutively performed: a) by an expert user in hand-held mode in standing as well as supine position, b) using the telerobotic arm without centrifugation as baseline and c) using the telerobotic arm during centrifugation. Vascular responses were compared between baseline and under centrifugation. Inter-, intra-registration and group variability have been assessed for hand-held and remotely controlled examination. The results show that intra-registration variability, σ h , was always smaller than inter-registration variability, σ m, that is in turned smaller than the inter-subject variability σ g (σ h < σ m < σ g). Centrifugation caused no significant changes in CCA diameter but a lower carotid distension compared to manual and robotic ultrasound in supine position (p < 0.05). Femoral diameter was significantly decreased in hypergravity compared to robotic sonography without centrifugation. A good reproducibility and precision of the remotely controlled vascular ultrasound assessment under centrifugation could be demonstrated. In conclusion, arterial wall dynamics can be precisely assessed for the CCA and femoral artery during centrifugation using a telerobotic ultrasound measurement system. Potential improvements to further enhance reproducibility and safety of the system are discussed.

Short-term Response of Serum Cartilage Oligomeric Matrix Protein to Different Types of Impact Loading Under Normal and Artificial Gravity.

Microgravity during long-term space flights induces degeneration of articular cartilage. Artificial gravity through centrifugation combined with exercise has been suggested as a potential countermeasure for musculoskeletal degeneration. The purpose of this study was to investigate the effect of different types of impact loading under normal and artificial gravity conditions on serum concentrations of cartilage oligomeric matrix protein (COMP), a biomarker of cartilage metabolism. Fifteen healthy male adults (26 ± 4 years, 181 ± 4 cm, 77 ± 6 kg) performed four different 30-min impact loading protocols on four experimental days: jumping with artificial gravity elicited by centrifugation in a short-arm centrifuge (AGJ), jumping with artificial gravity generated by low-pressure cylinders in a sledge jump system (SJS), vertical jumping under Earth gravity (EGJ), and running under Earth gravity (RUN). Five blood samples per protocol were taken: 30 min before, immediately before, immediately after, 30 min after, and 60 min after impact loading. Serum COMP concentrations were analyzed in these samples. During the impact exercises, ground reaction forces were recorded. Peak ground reaction forces were significantly different between the three jumping protocols (p < 0.001), increasing from AGJ (14 N/kg) to SJS (22 N/kg) to EGJ (29 N/kg) but were similar in RUN (22 N/kg) compared to SJS. The serum COMP concentration was increased (p < 0.001) immediately after all loading protocols, and then decreased (p < 0.001) at 30 min post-exercise compared to immediately after the exercise. Jumping and running under Earth gravity (EGJ and RUN) resulted in a significantly higher (p < 0.05) increase of serum COMP levels 30 min after impact loading compared to the impact loading under artificial gravity (RUN +30%, EGJ +20%, AGJ +17%, and SJS +13% compared to baseline). In conclusion, both the amplitude and the number of the impacts contribute to inducing higher COMP responses and are therefore likely important factors affecting cartilage metabolism. RUN had the largest effect on serum COMP concentration, presumably due to the high number of impacts, which was 10 times higher than for the jump modalities. Future studies should aim at establishing a dose-response relationship for different types of exercise using comparable amounts of impacts.

Tolerability of daily intermittent or continuous short-arm centrifugation during 60-day 6o head down bed rest (AGBRESA study).

Artificial gravity through short-arm centrifugation has potential as a multi-system countermeasure for deconditioning and cranial fluid shifts that may underlie ocular issues in microgravity. However, the optimal short-arm centrifugation protocol that is effective whilst remaining tolerable has yet to be determined. Given that exposure to centrifugation is associated with presyncope and syncope and in addition motion sickness an intermittent protocol has been suggested to be more tolerable. Therefore, we assessed cardiovascular loading and subjective tolerability of daily short arm centrifugation with either an intermittent or a continuous protocol during long-term head-down bed rest as model for microgravity exposure in a mixed sex cohort. During the Artificial Gravity Bed Rest with European Space Agency (AGBRESA) 60 day 6° head down tilt bed rest study we compared the tolerability of daily +1 Gz exposure at the center of mass centrifugation, either performed continuously for 30 minutes, or intermittedly (6 x 5 minutes). Heart rate and blood pressure were assessed daily during centrifugation along with post motion sickness scoring and rate of perceived exertion. During bed rest, 16 subjects (6 women, 10 men), underwent 960 centrifuge runs in total. Ten centrifuge runs had to be terminated prematurely, 8 continuous runs and 2 intermittent runs, mostly due to pre-syncopal symptoms and not motion sickness. All subjects were, however, able to resume centrifuge training on subsequent days. We conclude that both continuous and intermittent short-arm centrifugation protocols providing artificial gravity equivalent to +1 Gz at the center of mass is tolerable in terms of cardiovascular loading and motion sickness during long-term head down tilt bed rest. However, intermittent centrifugation appears marginally better tolerated, albeit differences appear minor.

Motion sickness symptoms during jumping exercise on a short-arm centrifuge.

Artificial gravity elicited through short-arm human centrifugation combined with physical exercise, such as jumping, is promising in maintaining health and performance during space travel. However, motion sickness symptoms could limit the tolerability of the approach. Therefore, we determined the feasibility and tolerability, particularly occurrence of motion sickness symptoms, during reactive jumping exercises on a short-arm centrifuge. In 15 healthy men, we assessed motion sickness induced by jumping exercises during short-arm centrifugation at constant +1Gz or randomized variable +0.5, +0.75, +1, +1.25 and +1.5 Gz along the body axis referenced to center of mass. Jumping in the upright position served as control intervention. Test sessions were conducted on separate days in a randomized and cross-over fashion. All participants tolerated jumping exercises against terrestrial gravity and on the short-arm centrifuge during 1 Gz or variable Gz at the center of mass without disabling motion sickness symptoms. While head movements markedly differed, motion sickness scores were only modestly increased with jumping on the short-arm centrifuge compared with vertical jumps. Our study demonstrates that repetitive jumping exercises are feasible and tolerable during short-arm centrifugation. Since jumping exercises maintain muscle and bone mass, our study enables further development of exercise countermeasures in artificial gravity.

Adaptability of a jump movement pattern to a non-constant force field elicited via centrifugation.

Humans are accustomed to Earth's constant gravitational acceleration of 1g. Here we assessed if complex movements such as jumps can be adapted to different acceleration levels in a non-constant force field elicited through centrifugation. Kinematics, kinetics and muscle activity of 14 male subjects (age 27±5years, body mass 77±6kg, height 181±7cm) were recorded during repetitive hopping in a short-arm human centrifuge for five different acceleration levels (0.5g, 0.75g, 1g, 1.25g, 1.5g). These data were compared to those recorded during normal hops on the ground, and hops in a previously validated sledge jump system. Increasing acceleration from 0.5g to 1.5g resulted in increased peak ground reaction forces (+80%, p<0.001), rate of force development (+100%, p<0.001) and muscle activity (+30 to +140%, depending on phase, side and muscle). However, most of the recorded parameters did not attain the level observed for jumps on the ground or in the jump system. For instance, peak forces during centrifugation with 1g amounted to 60% of the peak forces during jumps on the ground, ground contact time was prolonged by 90%, and knee joint excursions were reduced by 50%. We conclude that in principle, a quick adaptation to acceleration levels other than the normal constant gravitational acceleration of 1g is possible, even in the presence of a non-constant force field and Coriolis forces. However, centrifugation introduced additional constraints compared to a constant force field without rotation, resulting in lower peak forces and changes in kinematics. These changes can be interpreted as a movement strategy aimed at reducing lower limb deflections caused by Coriolis forces.

Differential gene expression of human chondrocytes cultured under short-term altered gravity conditions during parabolic flight maneuvers.

BACKGROUND: Chondrocytes are the main cellular component of articular cartilage. In healthy tissue, they are embedded in a strong but elastic extracelluar matrix providing resistance against mechanical forces and friction for the joints. Osteoarthritic cartilage, however, disrupted by heavy strain, has only very limited potential to heal. One future possibility to replace damaged cartilage might be the scaffold-free growth of chondrocytes in microgravity to form 3D aggregates. RESULTS: To prepare for this, we have conducted experiments during the 20th DLR parabolic flight campaign, where we fixed the cells after the first (1P) and the 31st parabola (31P). Furthermore, we subjected chondrocytes to isolated vibration and hypergravity conditions. Microarray and quantitative real time PCR analyses revealed that hypergravity regulated genes connected to cartilage integrity (BMP4, MMP3, MMP10, EDN1, WNT5A, BIRC3). Vibration was clearly detrimental to cartilage (upregulated inflammatory IL6 and IL8, downregulated growth factors EGF, VEGF, FGF17). The viability of the cells was not affected by the parabolic flight, but showed a significantly increased expression of anti-apoptotic genes after 31 parabolas. The IL-6 release of chondrocytes cultured under conditions of vibration was not changed, but hypergravity (1.8 g) induced a clear elevation of IL-6 protein in the supernatant compared with corresponding control samples. CONCLUSION: Taken together, this study provided new insights into the growth behavior of chondrocytes under short-term microgravity.

Moderate alterations of the cytoskeleton in human chondrocytes after short-term microgravity produced by parabolic flight maneuvers could be prevented by up-regulation of BMP-2 and SOX-9.

Real and simulated microgravity induce a variety of changes in human cells. Most importantly, changes in the cytoskeleton have been noted, and studies on microtubules have shown that they are gravisensitive. This study focuses on the effects of short-term real microgravity on gene expression, protein content, and cytoskeletal structure of human chondrocytes. We cultivated human chondrocytes, took them along a parabolic flight during the 24th Deutsches Zentrum für Luft- und Raumfahrt Parabolic (DLR) Flight Campaign, and fixed them after the 1st and the 31st parabola. Immunofluorescence microscopy revealed no changes after the 1st parabola, but disruptions of ß-tubulin, vimentin, and cytokeratin networks after the 31st parabola. No F-actin stress fibers were detected even after 31 parabolas. Furthermore, mRNA and protein quantifications after the 31st parabola showed a clear up-regulation of cytoskeletal genes and proteins. The mRNAs were significantly up-regulated as follows: TUBB, 2-fold; VIM, 1.3-fold; KRT8, 1.8-fold; ACTB, 1.9-fold; ICAM1, 4.8-fold; OPN, 7-fold; ITGA10, 1.5-fold; ITGB1, 1.2-fold; TGFB1, 1.5-fold; CAV1, 2.6-fold; SOX9, 1.7-fold; BMP-2, 5.3-fold. However, SOX5 (-25%) and SOX6 (-28%) gene expression was decreased. Contrary, no significant changes in gene expression levels were observed during vibration and hypergravity experiments. These data suggest that short-term microgravity affects the gene expression of distinct proteins. In contrast to poorly differentiated follicular thyroid cancer cells or human endothelial cells, chondrocytes only exert moderate cytoskeletal alterations. The up-regulation of BMP-2, TGF-ß1, and SOX9 in chondrocytes may play a key role in preventing cytoskeletal alterations.