1. Alterations in Muscle Contractile Properties, Structure, and Function During 10-Day Bed Rest, Post-Recovery, and Following COVID-19 LockdownBoštjan Šimunič, Martino V. Franchi, Fabio Sarto, Elena Monti, zaključena znanstvena zbirka raziskovalnih podatkov Povzetek: We aimed to identify early tensiomyography alterations in six muscles during a 10-day bed rest (BR10), followed by a 30-day recovery period (R+30), and to compare these changes with those observed after the 54-day COVID-19 lockdown in ten healthy males (22.9 ± 5.0 years). Tensiomyography and muscle thickness (sonography) were assessed at baseline, during bed rest, at BR10, R+30, and after the COVID-19 lockdown. Additional assessments included vertical jump performance (force plate), body composition (bioimpedance), physical activity (GPAQ), and lower back pain (VAS). By BR10, participants experienced a 1.9% body mass loss, a 3.8% increase in fat mass, and a 2.4% reduction in muscle mass. While anthropometric parameters returned to baseline by R+30, fat mass increased again by 3.9% post-lockdown. Jump height declined by 10.1% at BR10, returned to baseline at R+30, and remained stable thereafter. Muscle thickness decreased by 7.0% in the vastus lateralis at BR10 and by 10.1% post-lockdown. Tensiomyographic amplitude increased in all five leg muscles prior to BR10, recovered at R+30 and increased again after the COVID-19 lockdown, while a reduction was observed in the erector spinae within the first 48 hours, coinciding with reported lower back pain. In the erector spinae, both delay and contraction time decreased during BR10 and post-lockdown. In contrast, contraction time of the biceps femoris increased before BR10 and remained elevated post-lockdown. Overall, tensiomyographic parameters after the COVID-19 lockdown changed in the same direction as during bed rest, though to a lesser degree, make it a sensitive tool for detecting changes in muscle structural and functional quality after bed rest and reduced activity paradigms.
Ključne besede: Atrophy, Bed rest, Physical inactivity, Skeletal muscle, Tensiomyography
Objavljeno v DiRROS: 25.06.2025; Ogledov: 406; Prenosov: 0
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2. Mitochondrial sensitivity to submaximal [ADP] following bed rest : a novel two-phase approach associated with fibre typesLucrezia Zuccarelli, Maria De Martino, Antonio Filippi, Alice E. Knapton, Benjamin D. Thackray, Giovanni Baldassarre, Boštjan Šimunič, Rado Pišot, Giuseppe Sirago, Elena Monti, Marco Vincenzo Narici, Miriam Isola, Andrew J. Murray, Giovanna Lippe, Bruno Grassi, 2025, izvirni znanstveni članek Povzetek: Background: We recently demonstrated that following a 10-day exposure to inactivity/simulated microgravity impairments ofoxidative metabolism were located ‘upstream’ of mitochondrial function, as evaluated by maximal ADP-stimulated mitochon-drial respiration (JO 2max) determined ex vivo. The aim of this study was to evaluate mitochondrial sensitivity to submaximal[ADP] by an alternative approach aimed at identifying responses associated with fibre type composition.Methods: Isolated permeabilized vastus lateralis fibres were analysed by high-resolution respirometry in 9 young males beforeand after a 10-day horizontal bed rest. Eleven submaximal titrations of ADP (from 12.5 to 10 000 μM) were utilized to assess com-plex I + II-linked ADP sensitivity. We applied to JO 2 versus [ADP] data a traditional Michaelis–Menten kinetics equation, withthe calculation of the apparent K m and maximal respiration (Vmax), and two ‘sequential’ hyperbolic equations, yielding two K mand Vmax values. The two-hyperbolic equations were solved and the [ADP] value corresponding to 50% of JO 2max was calculated.Isoform expression of myosin heavy chains (MyHC) 1, 2A and 2X was also determined. Control experiments were also carriedout on rat skeletal muscle samples with different percentages of MyHC isoforms.Results: The two hyperbolic equations provided an alternative fitting of data and identified two distinct phases of the JO 2 versus[ADP] response: a first phase characterized by low Vmax (Vmax1 , 28 ± 10 pmol s−1 mg−1) and apparent K m (K m1 , 62 ± 54 μM) anda second phase characterized by higher Vmax (Vmax2 , 61 ± 16 pmol s−1 mg−1) and K m (K m2 , 1784 ± 833 μM). Data were confirmedin control experiments carried out in rat muscle samples with different percentages of MyHC isoforms. Correlation and receiveroperating characteristics analyses suggest that the two phases of the response were related to the % of MyHC isoforms.Conclusions: A novel mathematical approach (two sequential hyperbolic functions) for the fitting of JO 2 versus [ADP] data ob-tained by high-resolution respirometry on permeabilized skeletal muscle fibres, obtained in humans and rats, provided an alter-native fitting of the experimental data compared to the traditional Michaelis–Menten kinetics equation. This alternative modelallowed the identification of two distinct phases in the responses, which were related to fibre type composition. A first phase, characterized by low apparent K m and Vmax values, was correlated with the percentage of less oxidative (Type 2A + 2X) MyHCisoforms. A second phase, characterized by high apparent K m and Vmax , was related to more oxidative (Type 1) MyHC isoforms.
Ključne besede: ADP, bed rest, mitochondrial sensitivity, myosin heavy chains, skeletal muscle mitochondria
Objavljeno v DiRROS: 05.05.2025; Ogledov: 535; Prenosov: 299
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3. Interpersonal relationships as coping mechanisms during bed rest : a thematic synthesis literature reviewAna Cikač, Saša Pišot, 2024, izvirni znanstveni članek Povzetek: Bed rest (BR) studies are primarily designed to investigate the effects of weightlessness on the human body, but they are also used to study the effects of physical inactivity. For this purpose, participants are typically recruited from the general population without requiring specialized training, which contrasts with the selection process for cosmonauts. The BR study environment is often characterized as highly stressful, highlighting the importance of understanding coping mechanisms and adaptation strategies among participants, as well as the role of their daily interactions. This review aims to determine whether interpersonal relationships and the concept of social connectedness (SC) have been explored within the context of BR studies. For the search strategy, the definition of exclusion criteria, and the initial screening, PRISMA 2020 statement was followed. The PEO framework was used to generate keywords, and thematic synthesis was applied for data extraction, analysis, and synthesis. An initial search did not uncover any studies examining the concept of SC in the context of BR as an environment with extreme conditions, suggesting that SC in this context has not yet been investigated. While findings of thematic synthesis indicate that interpersonal relationships play a significant role in coping with and adapting to the extreme conditions of BR studies. As results showed these relationships can have both positive and negative effects. Interpersonal relationships also serve as a crucial support mechanism among participants. Additionally, how participants make sense of their involvement in such studies remains underexplored, and further research in this area is recommended in the discussion.
Ključne besede: bed rest, social connectedness, interpersonal relationships, coping mechanisms, thematic synthesis, literature review, social connectedness, interpersonal relationships, coping mechanisms, thematic synthesis, literature review
Objavljeno v DiRROS: 07.01.2025; Ogledov: 624; Prenosov: 341
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4. Retinal venular vessel diameters are smaller during ten days of bed restAdam Salon, Göktuğ Mert Çiftci, Damir Zubac, Boštjan Šimunič, Rado Pišot, Marco Vincenzo Narici, Per Morten Fredriksen, Benedicta Ngwenchi Nkeh-Chungag, Harald Sourij, Nandu Goswami, 2023, izvirni znanstveni članek Povzetek: Older individuals experience cardiovascular dysfunction during extended bedridden hospital or care home stays. Bed rest is also used as a model to simulate accelerated vascular deconditioning occurring during spacefight. This study investigates changes in retinal microcirculation during a tenday bed rest protocol. Ten healthy young males (22.9± 4.7 years; body mass index: 23.6± 2.5 kg·m–2) participated in a strictly controlled repeated-measures bed rest study lasting ten days. High-resolution images were obtained using a hand-held fundus camera at baseline, daily during the 10 days of bed rest, and 1 day after re-ambulation. Retinal vessel analysis was performed using a semi-automated software system to obtain metrics for retinal arteriolar and venular diameters, central retinal artery equivalent and central retinal vein equivalent, respectively. Data analysis employed a mixed linear model. At the end of the bed rest period, a signifcant decrease in retinal venular diameter was observed, indicated by a signifcantly lower central retinal vein equivalent (from 226.1 µm, CI 8.90, to 211.4 µm, CI 8.28, p= .026), while no signifcant changes in central retinal artery equivalent were noted. Prolonged bed rest confnement resulted in a signifcant (up to 6.5%) reduction in retinal venular diameter. These fndings suggest that the changes in retinal venular diameter during bedrest may be attributed to plasma volume losses and refect overall (cardio)-vascular deconditioning.
Ključne besede: eyes, retinal venular vessel, venske žile, bed rest, gibalna neaktivnost
Objavljeno v DiRROS: 23.11.2023; Ogledov: 1661; Prenosov: 713
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5. Environmental enrichment through virtual reality as multisensory stimulation to mitigate the negative effects of prolonged bed restLuka Šlosar, Manca Peskar, Rado Pišot, Uroš Marušič, 2023, pregledni znanstveni članek Povzetek: Prolonged bed rest causes a multitude of deleterious physiological changes in the human body that require interventions even during immobilization to prevent or minimize these negative effects. In addition to other interventions such as physical and nutritional therapy, non-physical interventions such as cognitive training, motor imagery, and action observation have demonstrated efficacy in mitigating or improving not only cognitive but also motor outcomes in bedridden patients. Recent technological advances have opened new opportunities to implement such non-physical interventions in semi- or fully-immersive environments to enable the development of bed rest countermeasures. Extended Reality (XR), which covers augmented reality (AR), mixed reality (MR), and virtual reality (VR), can enhance the training process by further engaging the kinesthetic, visual, and auditory senses. XR-based enriched environments offer a promising research avenue to investigate the effects of multisensory stimulation on motor rehabilitation and to counteract dysfunctional brain mechanisms that occur during prolonged bed rest. This review discussed the use of enriched environment applications in bedridden patients as a promising tool to improve patient rehabilitation outcomes and suggested their integration into existing treatment protocols to improve patient care. Finally, the neurobiological mechanisms associated with the positive cognitive and motor effects of an enriched environment are highlighted.
Ključne besede: physical inactivity, bed rest, nonphysical interventions, virtual reality
Objavljeno v DiRROS: 11.09.2023; Ogledov: 1452; Prenosov: 727
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6. Irisin attenuates muscle impairment during bed rest through muscle-adipose tissue crosstalkAndrea D'Amuri, Juana Maria Sanz, Stefano Lazzer, Rado Pišot, Boštjan Šimunič, Gianni Biolo, Giovanni Zuliani, Mladen Gasparini, Marco Vincenzo Narici, Bruno Grassi, Carlo Reggiani, Edoardo Dalla Nora, Angelina Passaro, 2022, izvirni znanstveni članek Povzetek: Simple Summary: Irisin is a known myokine secreted mainly by the muscle that is produced after physical activity. It induces browning in the adipose tissue with a consequent increase in mitochondrial oxidation of lipids and reduction of insulin resistance; thus, it has been hypothesized that irisin was the molecule mediating most of the beneficial effects related to exercise on adipose tissue and consequently on the whole organism. In our study we observed that extreme physical inactivity induces the loss of muscle mass and function, and an increase in the body adipose tissue as expected. However, of note, circulating irisin levels were increased secondary to enhanced irisin synthesis mainly from adipose tissue rather than muscle. In addition, subjects who produced more irisin had reduced muscle impairment. Therefore, our hypothesis is that there is negative feedback within the muscle-adipose tissue crosstalk, specifically not only does the muscle influence the adipose tissue through irisin during exercise, but also the adipose tissue protects the muscle during inactivity.Abstract: The detrimental effect of physical inactivity on muscle characteristics are well known. Irisin, an exercise-induced myokine cleaved from membrane protein fibronectin type III domain-containing protein-5 (FNDC5), mediates at least partially the metabolic benefits of exercise. This study aimed to assess the interplay between prolonged inactivity, circulating irisin, muscle performance, muscle fibers characteristics, as well as the FNDC5 gene expression (FNDC5ge) in muscle and adipose tissue among healthy subjects. Twenty-three healthy volunteers were tested before and after 14 days of Bed Rest, (BR). Post-BR circulating levels of irisin significantly increased, whereas body composition, muscle performance, and muscle fiber characteristics deteriorated. Among the subjects achieving the highest post-BR increase of irisin, the lowest reduction in maximal voluntary contraction and specific force of Fiber Slow/1, the highest increase of FNDC5ge in adipose tissue, and no variation of FNDC5ge in skeletal muscle were recorded. Subjects who had the highest FNDC5ge in adipose tissue but not in muscle tissue showed the highest circulating irisin levels and could better withstand the harmful effect of BR.
Ključne besede: physical inactivity, bed rest, FNDC5 gene expression, myokines, sarcopenia, muscles fiber
Objavljeno v DiRROS: 07.07.2022; Ogledov: 1943; Prenosov: 1108
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7. Early biomarkers of altered renal function and orthostatic intolerance during 10-day bedrestGrazia Tamma, Annarita Di Mise, Marianna Ranieri, Mariangela Centrone, Maria Venneri, Mariagrazia D'Agostino, Angela Ferrulli, Boštjan Šimunič, Marco Vincenzo Narici, Rado Pišot, Giovanna Valenti, 2022, izvirni znanstveni članek Povzetek: Exposure to actual or simulated microgravity results in alterations of renal function, fluid redistribution, and bone loss, which is coupled to a rise of urinary calcium excretion. We provided evidence that high calcium delivery to the collecting duct reduces local Aquaporin 2 (AQP2)-mediated water reabsorption under vasopressin action, thus limiting the maximal urinary concentration to reduce calcium saturation. To investigate early renal adaptation into simulated microgravity, we investigated the effects of 10 days of strict bedrest in 10 healthy volunteers. We report here that 10 days of inactivity are associated with a transient, significant decrease (day 5) in vasopressin (copeptin) paralleled by a decrease in AQP2 excretion, consistent with an increased central volume to the heart, resulting in reduced water reabsorption. Moreover, bedrest caused a significant increase in calciuria secondary to bone demineralization paralleled by a decrease in PTH. Urinary osteopontin, a glycoprotein exerting a protective effect on stone formation, was significantly reduced during bedrest. Moreover, a significant increase in adrenomedullin (day 5), a peptide with vasodepressor properties, was observed at day 5, which may contribute to the known reduced orthostatic capacity post-bedrest. We conclude that renal function is altered in simulated microgravity and is associated with an early increase in the risk of stone formation and reduced orthostatic capacity post-bedrest within a few days of inactivity.
Ključne besede: kidney, functions, bed rest, biomarkers, orthostatic intolerance, vasopressin, copeptin, aquaporin-2, adrenomedullin, calcium
Objavljeno v DiRROS: 20.04.2022; Ogledov: 1747; Prenosov: 1156
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8. The aging muscle in experimental bed rest : ǂa ǂsystematic review and meta-analysisFilippo Giorgio Di Girolamo, Nicola Fiotti, Zoran Milanović, Roberta Situlin, Filippo Mearelli, Pierandrea Vinci, Boštjan Šimunič, Rado Pišot, Marco Vincenzo Narici, Gianni Biolo, 2021, pregledni znanstveni članek Povzetek: Background: Maintaining skeletal muscle mass and function in aging is crucial for preserving the quality of life and health. An experimental bed rest (BR) protocol is a suitable model to explore muscle decline on aging during inactivity. Objective: The purpose of this systematic review and meta-analysis was, therefore, to carry out an up-to-date evaluation of bed rest, with a specific focus on the magnitude of effects on muscle mass, strength, power, and functional capacity changes as well as the mechanisms, molecules, and pathways involved in muscle decay. Design: This was a systematic review and meta-analysis study. Data sources: We used PubMed, Medline; Web of Science, Google Scholar, and the Cochrane library, all of which were searched prior to April 23, 2020. A manual search was performed to cover bed rest experimental protocols using the following key terms, either singly or in combination: %Elderly Bed rest,% %Older Bed rest,% %Old Bed rest,% %Aging Bed rest,% %Aging Bed rest,% %Bed-rest,% and %Bedrest%. Eligibility criteria for selecting studies: The inclusion criteria were divided into four sections: type of study, participants, interventions, and outcome measures. The primary outcome measures were: body mass index, fat mass, fat-free mass, leg lean mass, cross-sectional area, knee extension power, cytokine pattern, IGF signaling biomarkers, FOXO signaling biomarkers, mitochondrial modulation biomarkers, and muscle protein kinetics biomarkers. Results: A total of 25 studies were included in the qualitative synthesis, while 17 of them were included in the meta-analysis. In total, 118 healthy elderly volunteers underwent 5-, 7-, 10-, or 14-days of BR and provided a brief sketch on the possible mechanisms involved. In the very early phase of BR, important changes occurred in the skeletal muscle, with significant loss of performance associated with a lesser grade reduction of the total body and muscle mass. Meta-analysis of the effect of bed rest on total body mass was determined to be small but statistically significant (ES = %0.45, 95% CI: %0.72 to %0.19, P < 0.001). Moderate, statistically significant effects were observed for total lean body mass (ES = %0.67, 95% CI: %0.95 to %0.40, P < 0.001) after bed rest intervention. Overall, total lean body mass was decreased by 1.5 kg, while there was no relationship between bed rest duration and outcomes (Z = 0.423, p = 672). The meta-analyzed effect showed that bed rest produced large, statistically significant, effects (ES = %1.06, 95% CI: %1.37 to %0.75, P < 0.001) in terms of the knee extension power. Knee extension power was decreased by 14.65 N/s. In contrast, to other measures, meta-regression showed a significant relationship between bed rest duration and knee extension power (Z = 4.219, p < 0.001). Moderate, statistically significant, effects were observed after bed rest intervention for leg muscle mass in both old (ES = %0.68, 95% CI: %0.96 to %0.40, P < 0.001) and young (ES = %0.51, 95% CI: %0.80 to %0.22, P < 0.001) adults. However, the magnitude of change was higher in older (MD = %0.86 kg) compared to younger (MD = %0.24 kg) adults. Conclusion: Experimental BR is a suitable model to explore the detrimental effects of inactivity in young adults, old adults, and hospitalized people. Changes in muscle mass and function are the two most investigated variables, and they allow for a consistent trend in the BR-induced changes. Mechanisms underlying the greater loss of muscle mass and function in aging, following inactivity, need to be thoroughly investigated.
Ključne besede: bed rest, aging, muscles, muscle physiopathology, muscle function
Objavljeno v DiRROS: 26.08.2021; Ogledov: 2664; Prenosov: 1804
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