PerspectivesCommentaries on Viewpoint: Standardization of bed rest studies in the spaceflight contextPublished Online:22 Jul 2016MoreSectionsPDF (39 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Dag Linnarsson.Author AffiliationsKarolinska Institutet.COMMENTARY ON VIEWPOINT: STANDARDIZATION OF BED REST STUDIES IN THE SPACEFLIGHT CONTEXTto the editor: The work presented by Sundblad et al. (5) is important and is likely to improve present international efforts to develop countermeasures against, for example, cardiovascular deconditioning during spaceflight. However, one aspect that is not addressed to a sufficient extent is the experimental design of bed rest studies and to what extent they really mimic the daily working conditions of the astronauts. Astronauts are constantly physically and mentally active during daytime and participate in hours of physical training. In contrast, the subjects in most bed rest studies are not physically active. One consequence of this difference can be illustrated with an example from the cardiovascular field, namely the excitatory reflexes arising from isometric (ischemic) muscle action. In a study after 2 wk of bed rest Kamiya et al. (2) showed that such reflex responses from arm muscles were attenuated and even more so from leg muscles. Results from spaceflight studies of the cardiovascular responses to postexercise muscle ischemia are entirely different: no change in the responses to arm ischemia (3) and enhanced cardiovascular responses to leg ischemia (1). Providing similar examples, Ploutz-Snyder (4) recently pointed to the problem that this discrepancy between the daily activities during bed rest and spaceflight may have a negative impact on the practical relevance of data on countermeasure effects obtained during bed rest analogs. Likely, there are similar examples from other areas of physiology and if so that would speak in favor of a more flight-like daily activity pattern during bed rest analogs.REFERENCES1 Iellamo F, Di Rienzo M, Lucini D, Legramante JM, Pizzinelli P, Castiglioni P, Pigozzi F, Pagani M, Parati G. Muscle metaboreflex contribution to cardiovascular regulation during dynamic exercise in microgravity: insights from mission STS-107 of the space shuttle Columbia. J Physiol 572: 829–838, 2006. Crossref | ISI | Google Scholar2. Kamiya A, Michikami D, Shiozawa T, Iwase S, Hayano J, Kawada T, Sunagawa K, Mano T. Bed rest attenuates sympathetic and pressor responses to isometric exercise in antigravity leg muscles in humans. Am J Physiol Regul Integr Comp Physiol 286: R844–R850, 2004.Link | ISI | Google Scholar3. Karlsson L, Montmerle S, Rohdin M, Linnarsson D. Central command and metaboreflex cardiovascular responses to sustained handgrip during microgravity. Respir Physiol Neurobiol 169: S46–49, 2009.Crossref | ISI | Google Scholar4. Ploutz-Snyder LL. Evaluating countermeasures in spaceflight analogs. J Appl Physiol (1985) 120: 915–921, 2016.Link | ISI | Google Scholar5. Sundblad P, Orlov O, Angerer O, Larina I, Cromwell R. Viewpoint: Standardization of bed rest studies in the spaceflight context. J Appl Physiol; doi:10.1152/japplphysiol.00089.2016.Link | ISI | Google ScholarREFERENCES1 Iellamo F, Di Rienzo M, Lucini D, Legramante JM, Pizzinelli P, Castiglioni P, Pigozzi F, Pagani M, Parati G. Muscle metaboreflex contribution to cardiovascular regulation during dynamic exercise in microgravity: insights from mission STS-107 of the space shuttle Columbia. J Physiol 572: 829–838, 2006. Crossref | ISI | Google Scholar2. Kamiya A, Michikami D, Shiozawa T, Iwase S, Hayano J, Kawada T, Sunagawa K, Mano T. Bed rest attenuates sympathetic and pressor responses to isometric exercise in antigravity leg muscles in humans. Am J Physiol Regul Integr Comp Physiol 286: R844–R850, 2004.Link | ISI | Google Scholar3. Karlsson L, Montmerle S, Rohdin M, Linnarsson D. Central command and metaboreflex cardiovascular responses to sustained handgrip during microgravity. Respir Physiol Neurobiol 169: S46–49, 2009.Crossref | ISI | Google Scholar4. Ploutz-Snyder LL. Evaluating countermeasures in spaceflight analogs. J Appl Physiol (1985) 120: 915–921, 2016.Link | ISI | Google Scholar5. Sundblad P, Orlov O, Angerer O, Larina I, Cromwell R. Viewpoint: Standardization of bed rest studies in the spaceflight context. J Appl Physiol; doi:10.1152/japplphysiol.00089.2016.Link | ISI | Google ScholarLi Zuo and Chia-Chen Chuang.Author AffiliationsThe Ohio State University College of Medicine.PHYSIOLOGICAL ADAPTATIONS AND LIMITATIONS OF INDIVIDUAL BED REST STUDYto the editor: Bed rest model has been extensively used as a reliable stimulation to study spaceflight-related physiological alterations (2, 3). In response to microgravity, astronauts rapidly develop physiological adaptations such as skeletal muscle and cardiovascular deconditioning (2, 4). Particularly, declined muscle strength and aerobic fitness are often observed in the crew members (4). Much of the bed rest research aims to resolve the negative effects caused by gravitational unloading through the development of countermeasures (3). Although this microgravity analog setup is economical and practical for spaceflight physiology, bed rest studies have been carried out in diverse durations, operations, and interventions (3), thereby resulting in considerable variability in the data acquisition and analysis.We agree that establishing a standardized and systematic guideline for all bed rest studies is beneficial for comparing results in similar studies (5). The standardized experimental protocols and measurements also minimize potential variability in data collections. However, standardization may limit the flexibility of individual studies, thus likely reducing the possibility for innovative model improvements (4, 5). Additionally, standardized physiological measures may not be advisable for all subjects because of differences in the physiological or psychological conditions at the time of the participation. For example, the loss of muscle function is more prominent in older adults during a short-term bed rest (1). Standardization in international levels requires complex procedures and time-consuming efforts. Given both advantages and disadvantages, standardized bed rest studies should be employed with flexibility and caution (5).REFERENCES1. Coker RH, Hays NP, Williams RH, Wolfe RR, Evans WJ. Bed rest promotes reductions in walking speed, functional parameters, and aerobic fitness in older, healthy adults. J Gerontol A Biol Sci Med Sci 70: 91–96, 2015.Crossref | PubMed | ISI | Google Scholar2. Hargens AR, Vico L. Long-duration bed rest as an analog to microgravity. J Appl Physiol 120: 891–903, 2016.Link | ISI | Google Scholar3. Jost PD. Simulating human space physiology with bed rest. Hippokratia 12, Suppl 1: 37–40, 2008.PubMed | ISI | Google Scholar4. Ploutz-Snyder LL, Downs M, Ryder J, Hackney K, Scott J, Buxton R, Goetchius E, Crowell B. Integrated resistance and aerobic exercise protects fitness during bed rest. Med Sci Sports Exerc 46: 358–368, 2014.Crossref | ISI | Google Scholar5. Sundblad P, Orlov O, Angerer O, Larina IM, Cromwell R. Viewpoint: Standardization of bed rest studies in the spaceflight context. J Appl Physiol; doi:10.1152/japplphysiol.00089.2016, 2016.Link | Google ScholarREFERENCES1. Coker RH, Hays NP, Williams RH, Wolfe RR, Evans WJ. Bed rest promotes reductions in walking speed, functional parameters, and aerobic fitness in older, healthy adults. J Gerontol A Biol Sci Med Sci 70: 91–96, 2015.Crossref | PubMed | ISI | Google Scholar2. Hargens AR, Vico L. Long-duration bed rest as an analog to microgravity. J Appl Physiol 120: 891–903, 2016.Link | ISI | Google Scholar3. Jost PD. Simulating human space physiology with bed rest. Hippokratia 12, Suppl 1: 37–40, 2008.PubMed | ISI | Google Scholar4. Ploutz-Snyder LL, Downs M, Ryder J, Hackney K, Scott J, Buxton R, Goetchius E, Crowell B. Integrated resistance and aerobic exercise protects fitness during bed rest. Med Sci Sports Exerc 46: 358–368, 2014.Crossref | ISI | Google Scholar5. Sundblad P, Orlov O, Angerer O, Larina IM, Cromwell R. Viewpoint: Standardization of bed rest studies in the spaceflight context. J Appl Physiol; doi:10.1152/japplphysiol.00089.2016, 2016.Link | Google ScholarGuohua Li and Feng Gao.Author AffiliationsThe Fourth Military Medical University, China.REFLECTIONS ON STANDARDIZATION OF BED REST STUDIES IN THE SPACEFLIGHT CONTEXTto the editor: As pointed out by Sunblad et al. (5), bed rest studies need to be standardized in the spaceflight context. We agree that standardization will facilitate research and international cooperation by making future bed rest studies more easily reproducible while at the same time clarifying models which helps to cross-reference our data.As essential as standardization is flexibility. As the field for bed rest studies progresses, the influence of predisposing factors and gender differences on physiological adaptations of subjects has been confirmed (3, 4) and should be included in bed rest studies. For example, male and female test subjects have different susceptibility to spaceflight-induced visual impairment intracranial pressure syndrome (2).What's more, as the future of space exploration navigates into uncharted fields, bed rest study protocol should be adjusted accordingly to the aims of specialized missions. Previous research has focused more on the simulation of orbital flights, but simulation studies on manned planetary exploration is insufficient given how the trend is shifting. To increase our chances of successfully accomplishing future manned missions to the Moon/Mars, a ground-based analog that enables the study on physiological adaptations to partial gravity environment is necessary. However, existing bed rest models are unsatisfactory for partial gravity simulation because of the complete removal of lower extremity loads (1), and there are still many questions left unanswered concerning the reduced gravity environment (such as lunar 1/6 g). Therefore, flexibility in adjusting protocols, such as the tilt angle, is needed to better tailor studies for specific missions in the future.REFERENCES1. Cavanagh PR, Rice AJ, Licata AA, Kuklis MM, Novotny SC, Genc KO, Englehaupt RK, Hanson AM. A novel lunar bed rest analogue. Aviat Space Environ Med 84: 1191–1195, 2013.Crossref | Google Scholar2. Mader TH, Gibson CR, Pass AF, Kramer LA, Lee AG, Fogarty J, Tarver WJ, Dervay JP, Hamilton DR, Sargsyan A, Phillips JL, Tran D, Lipsky W, Choi J, Stern C, Kuyumjian R, Polk JD. Optic disc edema, globe flattening, choroidal folds, and hyperopic shifts observed in astronauts after long-duration space flight. Ophthalmology 118: 2058–2069, 2011.Crossref | PubMed | ISI | Google Scholar3. Mark S, Scott GB, Donoviel DB, Leveton LB, Mahoney E, Charles JB, Siegel B. The impact of sex and gender on adaptation to space: executive summary. J Womens Health (Larchmt) 23: 941–947, 2014.Crossref | ISI | Google Scholar4. Pavy-Le TA, Heer M, Narici MV, Rittweger J, Vernikos J. From space to Earth: advances in human physiology from 20 years of bed rest studies (1986–2006). Eur J Appl Physiol 101: 143–194, 2007.Crossref | ISI | Google Scholar5. Sundblad P, Orlov O, Angerer O, Larina IM, Cromwell R. Viewpoint: Standardization of bed rest studies in the spaceflight context. J Appl Physiol; doi:10.1152/japplphysiol.00089.2016.Crossref | ISI | Google ScholarREFERENCES1. Cavanagh PR, Rice AJ, Licata AA, Kuklis MM, Novotny SC, Genc KO, Englehaupt RK, Hanson AM. A novel lunar bed rest analogue. Aviat Space Environ Med 84: 1191–1195, 2013.Crossref | Google Scholar2. Mader TH, Gibson CR, Pass AF, Kramer LA, Lee AG, Fogarty J, Tarver WJ, Dervay JP, Hamilton DR, Sargsyan A, Phillips JL, Tran D, Lipsky W, Choi J, Stern C, Kuyumjian R, Polk JD. Optic disc edema, globe flattening, choroidal folds, and hyperopic shifts observed in astronauts after long-duration space flight. Ophthalmology 118: 2058–2069, 2011.Crossref | PubMed | ISI | Google Scholar3. Mark S, Scott GB, Donoviel DB, Leveton LB, Mahoney E, Charles JB, Siegel B. The impact of sex and gender on adaptation to space: executive summary. J Womens Health (Larchmt) 23: 941–947, 2014.Crossref | ISI | Google Scholar4. Pavy-Le TA, Heer M, Narici MV, Rittweger J, Vernikos J. From space to Earth: advances in human physiology from 20 years of bed rest studies (1986–2006). Eur J Appl Physiol 101: 143–194, 2007.Crossref | ISI | Google Scholar5. Sundblad P, Orlov O, Angerer O, Larina IM, Cromwell R. Viewpoint: Standardization of bed rest studies in the spaceflight context. J Appl Physiol; doi:10.1152/japplphysiol.00089.2016.Crossref | ISI | Google ScholarPolona Jaki Mekjavic, Harminder Dua, Winfried Amoaku, Ian A. Macdonald, Ola Eiken, and Igor B. Mekjavic.Author AffiliationsUniversity Medical Centre Ljubljana, Slovenia.OPHTHALMOLOGICAL EXCLUSION CRITERIAto the editor: Since the report of visual impairment observed in astronauts by Madder and colleagues (2), the resolution of the etiology of Microgravity Ocular Syndrome (MOS) has become a priority in Space Life Sciences. Studies assessing the contribution of stressors associated with space habitats are now being included in bed rest studies (1, 3, 7). Because the focus of bed rest studies is also on the evaluation of the efficacy of countermeasures to mitigate the microgravity-induced musculoskeletal atrophy and cardiovascular deconditioning (4) and in future also the prevention of visual impairment, it is essential that not only the bed rest protocols, but also the subject pool, be standardized (5, 6). For the purpose of investigating the effect of inactivity/unloading on the morphology and function of the eyes, and the efficacy of countermeasures in alleviating such effects, it is in our opinion essential that future editions of the standardization document specify the following ophthalmological exclusion criteria, in addition to the existing exclusion criteria in the bed rest guidelines: Best corrected visual acuity (BCVA) ≤ 0.8;Refractive error of spherical equivalent > ±3 dioptres;Ocular motility disorders, including diplopia;Color blindness;Lid lag, lagophthalmos, blepharitis;Dry eye disease;Corneal ectasias or dystrophies;Glaucoma;Uveitides;Chorio retinal diseases;Optic nerve disease;Orbital pathology (like dysthyroid);Ongoing medication, topical or systemic, for eye condition;Any previous eye surgery that might influence the study outcome;Any eye disease affecting visual function or ocular motility;Any retinal disease.REFERENCES1. Jaki Mekjavic P, Lenassi E, Eiken O, Mekjavic IB. FemHab: Effect of acute hypercapnia during 10-d hypoxic bed rest on posterior eye structures. J Appl Physiol 120: 1241–1248, 2016.Link | ISI | Google Scholar2. Mader TH, Gibson CR, Pass AF, Kramer LA, Lee AG, Fogarty J, Tarver WJ, Dervay JP, Hamilton DR, Sargsyan A, Phillips JL, Tran D, Lipsky W, Choi J, Stern C, Kuyumjian R, Polk JD. Optic disc edema, globe flattening, choroidal folds, and hyperopic shifts observed in astronauts after long-duration space flight. Ophthalmology 118: 2058–2069, 2011.Crossref | PubMed | ISI | Google Scholar3. Marshall-Bowman K, Barratt MR, Gibson CR. Ophthalmic changes and increased intracranial pressure associated with long duration spaceflight: an emerging understanding. Acta Astronautica 87: 77–87, 2013.Crossref | ISI | Google Scholar4. Ploutz-Snyder L. Evaluating countermeasures in spaceflight analogs. J Appl Physiol 120: 915–921, 2016.Link | ISI | Google Scholar5. Sundblad P (editor). Guidelines for Standardization of Bed Rest Studies in the Spaceflight Context. International Academy of Astronautics, ISBN/EAN IAA: 9782917761342. June 2015.Google Scholar6. Sundblad P, Orlov O, Angerer O, Larina I, Cromwell R. Viewpoint: Standardization of bed rest studies in the spaceflight context. J Appl Physiol; doi:10.1152/japplphysiol.00089.2016.Link | ISI | Google Scholar7. Taibbi G, Cromwell RL, Kapoor Godley BF, Vizzeri G. The effect of microgravity on ocular structures and visual function: A review. Surv Ophthalmol 58: 155–163, 2013.Crossref | PubMed | ISI | Google ScholarREFERENCES1. Jaki Mekjavic P, Lenassi E, Eiken O, Mekjavic IB. FemHab: Effect of acute hypercapnia during 10-d hypoxic bed rest on posterior eye structures. J Appl Physiol 120: 1241–1248, 2016.Link | ISI | Google Scholar2. Mader TH, Gibson CR, Pass AF, Kramer LA, Lee AG, Fogarty J, Tarver WJ, Dervay JP, Hamilton DR, Sargsyan A, Phillips JL, Tran D, Lipsky W, Choi J, Stern C, Kuyumjian R, Polk JD. Optic disc edema, globe flattening, choroidal folds, and hyperopic shifts observed in astronauts after long-duration space flight. Ophthalmology 118: 2058–2069, 2011.Crossref | PubMed | ISI | Google Scholar3. Marshall-Bowman K, Barratt MR, Gibson CR. Ophthalmic changes and increased intracranial pressure associated with long duration spaceflight: an emerging understanding. Acta Astronautica 87: 77–87, 2013.Crossref | ISI | Google Scholar4. Ploutz-Snyder L. Evaluating countermeasures in spaceflight analogs. J Appl Physiol 120: 915–921, 2016.Link | ISI | Google Scholar5. Sundblad P (editor). Guidelines for Standardization of Bed Rest Studies in the Spaceflight Context. International Academy of Astronautics, ISBN/EAN IAA: 9782917761342. June 2015.Google Scholar6. Sundblad P, Orlov O, Angerer O, Larina I, Cromwell R. Viewpoint: Standardization of bed rest studies in the spaceflight context. J Appl Physiol; doi:10.1152/japplphysiol.00089.2016.Link | ISI | Google Scholar7. Taibbi G, Cromwell RL, Kapoor Godley BF, Vizzeri G. The effect of microgravity on ocular structures and visual function: A review. Surv Ophthalmol 58: 155–163, 2013.Crossref | PubMed | ISI | Google Scholar Download PDF Previous Back to Top Next FiguresReferencesRelatedInformation More from this issue > Volume 121Issue 1July 2016Pages 350-351 Copyright & PermissionsCopyright © 2016 the American Physiological Societyhttps://doi.org/10.1152/japplphysiol.00439.2016PubMed27451275History Published online 22 July 2016 Published in print 1 July 2016 Metrics