Abstract
Bed rest studies of the past 20 years are reviewed. Head-down bed rest (HDBR) has proved its usefulness as a reliable simulation model for the most physiological effects of spaceflight. As well as continuing to search for better understanding of the physiological changes induced, these studies focused mostly on identifying effective countermeasures with encouraging but limited success. HDBR is characterised by immobilization, inactivity, confinement and elimination of Gz gravitational stimuli, such as posture change and direction, which affect body sensors and responses. These induce upward fluid shift, unloading the body’s upright weight, absence of work against gravity, reduced energy requirements and reduction in overall sensory stimulation. The upward fluid shift by acting on central volume receptors induces a 10–15% reduction in plasma volume which leads to a now well-documented set of cardiovascular changes including changes in cardiac performance and baroreflex sensitivity that are identical to those in space. Calcium excretion is increased from the beginning of bed rest leading to a sustained negative calcium balance. Calcium absorption is reduced. Body weight, muscle mass, muscle strength is reduced, as is the resistance of muscle to insulin. Bone density, stiffness of bones of the lower limbs and spinal cord and bone architecture are altered. Circadian rhythms may shift and are dampened. Ways to improve the process of evaluating countermeasures—exercise (aerobic, resistive, vibration), nutritional and pharmacological—are proposed. Artificial gravity requires systematic evaluation. This review points to clinical applications of BR research revealing the crucial role of gravity to health.
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Aaslid R, Lindegaard KF, Sorteberg W, Nornes H (1989) Cerebral autoregulation dynamics in humans. Stroke 20:45–52
Abe T, Kawakami Y, Suzuki Y, Gunji A, Fukunaga T (1997) Effects of 20 days bed rest on muscle morphology. J Gravit Physiol 4:125–126
Akima H, Kuno S, Suzuki Y, Gunji A, Fukunaga T (1997) Effects of 20 days of bed rest on physiological cross-sectional area of human thigh and leg muscles evaluated by magnetic resonance imaging. J Gravit Physiol 4:15–21
Akima H, Kubo K, Kanehisa H, Suzuki Y, Gunji A, Fukunaga T (2000) Leg-press resistance training during 20 days of 6 degrees head-down-tilt bed rest prevents muscle deconditioning. Eur J Appl Physiol 82:30–38
Akima H, Kubo K, Imai M, Kanehisa H, Suzuki Y, Gunji A, Fukunaga T (2001) Inactivity and muscle: effect of resistance training during bed rest on muscle size in the lower limb. Acta Physiol Scand 172:269–278
Akima H, Ushiyama J, Kubo J, Tonosaki S, Itoh M, Kawakami Y, Fukuoka H, Kanehisa H, Fukunaga T (2003) Resistance training during unweighting maintains muscle size and function in human calf. Med Sci Sports Exerc 35:655–662
Akima H, Katayama K, Sato K, Ishida K, Masuda K, Takada H, Watanabe Y, Iwase S (2005) Intensive cycle training with artificial gravity maintains muscle size during bed rest. Aviat Space Environ Med 76:923–929
Alkner BA, Tesch PA (2004a) Efficacy of a gravity-independent resistance exercise device as a countermeasure to muscle atrophy during 29-day bed rest. Acta Physiol Scand 181:345–357
Alkner BA, Tesch PA (2004b) Knee extensor and plantar flexor muscle size and function following 90 days of bed rest with or without resistance exercise. Eur J Appl Physiol 93:294–305
Alonso A, Fernandez Y, Fernandez R, Ordonez P, Moreno M, Diaz F, Patterson AM, Gonzalez C (2005) Effect of food restriction on the insulin signalling pathway in rat skeletal muscle and adipose tissue. J Nutr Biochem 16(10):602–609
Andersen JL, Gruschy-Knudsen T, Sandri C, Larsson L, Schiaffino S (1999) Bed rest increases the amount of mismatched fibers in human skeletal muscle. J Appl Physiol 86:455–460
Arbeille P, Gauquelin G, Pottier JM, Pourcelot L, Guell A, Gharib C (1992) Results of a 4-week head-down tilt with and without LBNP countermeasure: II. Cardiac and peripheral hemodynamics comparison with a 25-day spaceflight. Aviat Space Environ Med 63:9–13
Arbeille P, Fomina G, Roumy J, Alferova I, Tobal N, Herault S (2001) Adaptation of the left heart, cerebral and femoral arteries, and jugular and femoral veins during short-and long-term head-down tilt and spaceflights. Eur J Appl Physiol 86:157–168
Arbeille P, Sigaudo D, Pavy Le Traon A, Herault S, Porcher M, Gharib C (1998) Femoral to cerebral arterial blood flow redistribution and femoral vein distension during orthostatic tests after 4 days in the head-down tilt position or confinement. Eur J Appl Physiol Occup Physiol 78:208–218
Arnaud SB, Morey-Holton E (1990) Gravity, calcium, and bone: Update 1989. Physiologist 33:S65–S68
Arnaud SB, Wolinsky I, Fung P, Vernikos J (2000) Dietary salt and urinary calcium excretion in a human bed rest spaceflight model. Aviat Space Environ Med 71:1115–1119
Arnett T (2003) Regulation of bone cell function by acid-base balance. Proc Nutr Soc 62:511–520
Arnett TR, Dempster DW (1986) Effect of pH on bone resorption by rat osteoclasts in vitro. Endocrinology 119:119–124
Atkov OY, Bednenko VS (1992) Hypokinesia and weightlessness: clinical and physiologic aspects. International University Press, Madison, 560 pp
Baecker N, Tomic A, Mika C, Gotzmann A, Platen P, Gerzer R, Heer M (2003) Bone resorption is induced on the second day of bedrest: results of a controlled crossover trial. Jappl Physiol 95:977–982
Baker D, Roberts R, Towell T (2000) Factors predictive of bone mineral density in eating-disordered women: a longitudinal study. Int J Eat Disord 27:29–35
Bamman MM, Hunter GR, Stevens BR, Guilliams ME, Greenisen MC (1997) Resistance exercise prevents plantar flexor deconditioning during bed rest. Med Sci Sports Exerc 29:1462–1468
Bamman MM, Clarke MS, Feeback DL, Talmadge RJ, Stevens BR, Lieberman SA, Greenisen MC (1998) Impact of resistance exercise during bed rest on skeletal muscle sarcopenia and myosin isoform distribution. J Appl Physiol 84:157–163
Barbe P, Galitzky J, De Glisezinski I, Riviere D, Thalamas C, Senard JM, Crampes F, Lafontan M, Berlan M (1998) Simulated microgravity increases beta-adrenergic lipolysis in human adipose tissue. J Clin Endocrinol Metab 83:619–625
Barbe P, Galitzky J, Thalamas C, Langin D, Lafontan M, Senard JM, Berlan M (1999) Increase in epinephrine-induced responsiveness during microgravity simulated by head-down bed rest in humans. J Appl Physiol 87:1614–1620
Bartok C, Atkinson RL, Schoeller DA (2003) Measurement of nutritional status in simulated microgravity by bioelectrical impedance spectroscopy. J Appl Physiol 95:225–232
Baum K, Essfeld D (1999) Origin of back pain during bedrest: a new hypothesis. Eur J Med Res 4:389–393
Beckett WS, Vroman NB, Nigro D, Thompson-Gorman S, Wilkerson JE, Fortney SM (1986) Effect of prolonged bed rest on lung volume in normal individuals. J Appl Physiol 61:919–925
Belin de Chantemele E, Blanc S, Pellet N, Duvareille M, Ferretti G, Gauquelin-Koch G, Gharib C, Custaud MA (2004a) Does resistance exercise prevent body fluid changes after a 90-day bed rest? Eur J Appl Physiol 92:555–564
Belin de Chantemele E, Pascaud L, Custaud MA, Capri A, Louisy F, Ferretti G, Gharib C, Arbeille P (2004b) Calf venous volume during stand-test after a 90-day bed-rest study with or without exercise countermeasure. J Physiol 561:611–622
Berg HE, Tesch PA (1996) Changes in muscle function in response to 10 days of lower limb unloading in humans. Acta Physiol Scand 157:63–70
Berg HE, Dudley GA, Haggmark T, Ohlsen H, Tesch PA (1991) Effects of lower limb unloading on skeletal muscle mass and function in humans. J Appl Physiol 70:1882–1885
Berg HE, Tedner B, Tesch PA (1993) Changes in lower limb muscle cross-sectional area and tissue fluid volume after transition from standing to supine. Acta Physiol Scand 148:379–385
Berg HE, Larsson L, Tesch PA (1997) Lower limb skeletal muscle function after 6 wk of bed rest. J Appl Physiol 82:182–188
Berry P, Berry I, Manelfe C (1993) Magnetic resonance imaging evaluation of lower limb muscles during bed rest: a microgravity simulation model. Aviat Space Environ Med 64:212–218
Bertinieri G, di Rienzo M, Cavallazzi A, Ferrari AU, Pedotti A, Mancia G (1985) A new approach to analysis of the arterial baroreflex. J Hypertens 3(Suppl):79–81
Bestle MH, Norsk P, Bie P (2001) Fluid volume and osmoregulation in humans after a week of head-down bed rest. Am J Physiol Regul Integr Comp Physiol 281:310–317
Biering-Sorensen F, Bohr HH, Schaadt OP (1990) Longitudinal study of bone mineral content in the lumbar spine, the forearm and the lower extremities after spinal cord injury. Eur J Clin Invest 20:330–335
Biolo G, De Cicco M (2004) Muscle mass and protein metabolism. Nestle Nutr Workshop Ser Clin Perform Programme, pp 111–120
Biolo G, Declan Fleming RY, Wolfe RR (1995a) Physiologic hyperinsulinemia stimulates protein synthesis and enhances transport of selected amino acids in human skeletal muscle. J Clin Invest 95:811–819
Biolo G, Maggi SP, Williams BD, Tipton KD, Wolfe RR (1995b) Increased rates of muscle protein turnover and amino acid transport after resistance exercise in humans. Am J Physiol 268:514–520
Biolo G, Williams BD, Fleming RY, Wolfe RR (1999) Insulin action on muscle protein kinetics and amino acid transport during recovery after resistance exercise. Diabetes 48:949–957
Biolo G, Ciocchi B, Lebenstedt M, Heer M, Guarnieri G (2003) Sensitivity of whole body protein synthesis to amino acid administration during short-term bed rest. J Gravit Physiol 9:197–198
Biolo G, Ciocchi B, Lebenstedt M, Barazzoni R, Zanetti M, Platen P, Heer M, Guarnieri G (2004) Short-term bed rest impairs amino acid-induced protein anabolism in humans. J Physiol 558:381–388
Bjarnason NH, Christiansen C (2000) Early response in biochemical markers predicts long-term response in bone mass during hormone replacement therapy in early postmenopausal women. Bone 26:561–569
Blaber AP, Bondar RL, Kassam MS (2004) Heart rate variability and short duration spaceflight: relationship to post-flight orthostatic intolerance. BMC Physiol 27:4–6
Blanc S, Normand S, Ritz P, Pachiaudi C, Vico L, Gharib C, Gauquelin-Koch G (1998) Energy and water metabolism, body composition and hormonal changes induced by 42 days of enforced inactivity and simulated weightlessness. J Clin Endocrinol Metab 83:4289–4297
Blanc S, Normand S, Pachiaudi C, Fortrat JO, Laville M, Gharib C (2000) Fuel homeostasis during physical inactivity induced by bed rest. J Clin Endocrinol Metab 85:2223–2233
Blecker MW, De groot PC, Pawelczyk JA, Hopman MT, Levine BD (2004) Effects of 18 days of bed rest on leg and arm venous properties. J Appl Physiol 96:840–847
Bloomfield SA, Girten BE, Weisbrode SE (1997) Effects of vigorous exercise training and beta-agonist administration on bone response to hindlimb suspension. J Appl Physiol 83:172–178
Bone HG, Greenspan SL, McKeever C, Bell N, Davidson M, Downs RW, Emkey R, Meunier PJ, Miller SS, Mulloy AL, Recker RR, Weiss SR, Heyden N, Musliner T, Suryawanshi S, Yates AJ, Lombardi A (2000) Alendronate and estrogen effects in postmenopausal women with low bone mineral density: Alendronate/Estrogen Study Group. J Clin Endocrinol Metab 85:720–726
Bonnin P, Ben Driss A, Benessiano J, Maillet A, Pavy le Traon A, Levy BI (2001) Enhanced flow-dependent vasodilatation after bed rest, a possible mechanism for orthostatic intolerance in humans. Eur J Appl Physiol 85:420–426
Booth SL, Tucker KL, Chen H, Hannan MT, Gagnon DR, Cupples LA, Wilson PW, Ordovas J, Schaefer EJ, Dawson-Hughes B, Kiel DP (2000) Dietary vitamin K intakes are associated with hip fracture but not with bone mineral density in elderly men and women. Am J Clin Nutr 71:1201–1208
Booth SL, Broe KE, Gagnon DR, Tucker KL, Hannan MT, McLean RR, Dawson-Hughes B, Wilson PW, Cupples LA, Kiel DP (2003) Vitamin K intake and bone mineral density in women and men. Am J Clin Nutr 77:512–516
Bourland CT, Kloeris V, Rice BL, Vodovotz Y (2000) Food systems for space and planetary flights. In: Lane HW, Schoeller DA (eds) Nutrition in spaceflight and weightlessness models, 1st edn. CRC press, Boca Raton, pp 19–40
Braam LA, Knapen MH, Geusens P, Brouns F, Hamulyak K, Gerichhausen MJ, Vermeer C (2003) Vitamin K1 supplementation retards bone loss in postmenopausal women between 50 and 60 years of age. Calcif Tissue Int 73:21–26
Branch JD 3rd, Pate RR, Bodary PF, Convertino VA (1998) Red cell volume and erythropoietin responses during exposure to simulated microgravity. Aviat Space Environ Med 69:347–351
Bungo MW, Charles JB, Johnson PC Jr (1985) Cardiovascular deconditioning during space flight and the use of saline as a countermeasure to orthostatic intolerance. Aviat Space Environ Med 56:985–990
Burger EH, Klein-Nulend J, Smit TH (2003) Strain-derived canalicular fluid flow regulates osteoclast activity in a remodelling osteon: a proposal. J Biomech 36:1453–1459
Burton RR (1997) Taking gravity into Space. J Gravit Physiol 4(2):17–20
Burton RR, Meeker LJ (1992) Physiologic validation of a short-arm centrifuge for space applications. Aviat Space Environ Med 63:476–481
Caillot-Augusseau A, Lafage-Proust MH, Margaillan P, Vergely N, Faure S, Paillet S, Lang F, Alexandre C, Estour B (2000a) Weight gain reverses bone turnover and restores circadian variation of bone resorption in anorexic patients. Clin Endocrinol (Oxf) 52:113–121
Caillot-Augusseau A, Vico L, Heer M, Voroviev D, Souberbielle JC, Zitterman A, Alexandre C, Lafage-Proust MH (2000b) Space flight is associated with rapid decreases of undercarboxylated osteocalcin and increases of markers of bone resorption without changes in their circadian variation: observations in two cosmonauts. Clin Chem 46:1136–1143
Caruso JF, Hamill JL, Yamauchi M, Cook TD, Mercado DR, Gibb G, Higginson BK, Elias J, Hernandez DA (2004) Can albuterol help resistance exercise attenuate unloading-induced bone loss? J Strength Cond Res 18:753–759
Chappard D, Alexandre C, Palle S, Vico L, Morukov BV, Rodionova SS, Minaire P, Riffat G (1989) Effects of a bisphosphonate (1-hydroxy ethylidene-1, 1 bisphosphonic acid) on osteoclast number during prolonged bed rest in healthy humans. Metabolism 38:822–825
Chee WS, Suriah AR, Chan SP, Zaitun Y, Chan YM (2003) The effect of milk supplementation on bone mineral density in postmenopausal Chinese women in Malaysia. Osteoporos Int 14:828–834
Chopard A, Arrighi N, Carnino A, Marini JF (2005) Changes in dysferlin, proteins from dystrophin glycoprotein complex, costameres, and cytoskeleton in human soleus and vastus lateralis muscles after a long-term bedrest with or without exercise. FASEB J 19:1722–1744
Chou JL, Leftheriotis GPN, Stad NJ, Arndt NF, Jackson CGR, Simmonson S, Barnes PR, Greenleaf JE (1998) Human physiological responses to cycle ergometer leg exercise during + Gz acceleration. NASA/TM-112237, pp 1–22
Clement G, Pavy-Le Traon A (2004) Centrifugation as a counter-measure during actual and simulated microgravity: a review. Eur J Appl Physiol 92:235–248
Convertino VA (1991) Carotid-cardiac baroreflex: relation with orthostatic hypotension following simulated microgravity and implications for development of countermeasures. Acta Astronaut 23:9–17
Convertino VA (1992) Effects of exercise and inactivity on intravascular volume and cardiovascular control mechanisms. Acta Astronaut 27:123–129
Convertino VA (1993) Cardiovascular consequences of bed rest: effect on maximal oxygen uptake. Aviat Space Environ Med 64:275–286
Convertino VA (1995) Exercise and adaptation to microgravity environment. In: Fregly MJ, Blatteis CM (eds) Handbook of physiology: environmental physiology. III: The gravitational environment. vol. 2, Chap. 36. Oxford University Press, New York, pp 815–843
Convertino VA (1996) Clinical aspects of the control of plasma volume at microgravity and during return to one gravity. Med Sci Sports Exerc 28(Suppl):45–52
Convertino VA (1997) Cardiovascular consequences of bed rest: effect on maximal oxygen uptake. Med Sci Sports Exerc 29:191–196
Convertino VA (1999) G-factor as a tool in basic research: mechanisms of orthostatic tolerance. J Gravit Physiol 6:73–76
Convertino VA (2002a) Carotid-cardiac baroreflex: relation with orthostatic hypotension following simulated microgravity and implications for development of countermeasures. Am J Physiol Heart Circ Physiol 282:2210–2215
Convertino VA (2002b) Mechanisms of microgravity induced orthostatic intolerance: implications for effective countermeasures. J Grav Physiol 9:1–14
Convertino VA, Cooke WH (2005) Evaluation of cardiovascular risks of spaceflight does not support the NASA bioastronautics critical path roadmap. Aviat Space Environ Med 76:869–876
Convertino VA, Goldwater DJ, Sandler H (1986) Bedrest-induced peak VO2 reduction associated with age, gender, and aerobic capacity. Aviat Space Environ Med 57:17–22
Convertino VA, Eckberg DL, Fritsch JM, Vernikos-Danellis J (1990) Head-down bed rest impairs vagal baroreflex responses and provokes orthostatic hypotension. J Appl Physiol 68:1458–1464
Convertino VA, Doerr DF, Vernikos J (1994a) Altered baroreflex control of forearm vascular resistance during simulated microgravity. J Gravit Physiol 1:31–32
Convertino VA, Doerr DF, Ludwig DA, Vernikos J (1994b) Effect of simulated microgravity on cardiopulmonary baroreflex control of forearm vascular resistance. Am J Physiol 266:1962–1969
Convertino VA, Polet JL, Engelke KA, Hoffler GW, Lane LD, Blomqvist CG (1997a) Evidence for increased beta-adrenoreceptor responsiveness induced by 14 days of simulated microgravity in humans. Am J Physiol 273:93–99
Convertino VA, Preyje FA, Ludwigh DA, Engelken FJ (1997b) Effects of vestibular and oculomotor stimulation on responsiveness of the carotid-cardiac baroreflex. Am J physiol 273:615–622
Convertino VA, Bloomfield SA, Greenleaf JE (1997c) An overview of the issues: physiological effects of bed rest and restricted physical activity. Med Sci Sports Exerc 29:187–190
Convertino VA, Luetkemeier MJ, Elliott JJ, Ludwig DA, Wade CE (2000) Renal responsiveness to aldosterone during exposure to simulated microgravity. J Appl Physiol 89:1737–1743
Cosman F (2005) Anabolic therapy for osteoporosis: parathyroid hormone. Curr Osteoporos Rep 3:143–149
Cowell SA, Stocks JM, Evans DG, Simonson SR, Greenleaf JE (2002) The exercise and environmental physiology of extravehicular activity. Aviat Space Environ Med 73:54–67
Crandall CG, Engelke KA, Convertino VA, Raven PB (1994) Aortic baroreflex control of heart rate after 15 days of simulated microgravity exposure. J Appl Physiol 77:2134–2139
Crandall CG, Shibasaki M, Wilson TE, Cui J, Levine BD (2003) Prolonged head-down tilt exposure reduces maximal cutaneous vasodilator and sweating capacity in humans. J Appl Physiol 94:2330–2336
Cumming RG, Nevitt MC (1997) Calcium for prevention of osteoporotic fractures in postmenopausal women. J Bone Miner Res 12:1321–1329
Custaud MA, Millet C, Frutoso J, Maillet A, Gauquelin G, Gharib C, Fortrat JO (2000) No effect of venoconstrictive thigh cuffs on orthostatic hypotension induced by head-down bed rest. Acta Physiol Scand 170:77–85
Custaud MA, de Souza Neto EP, Albry P, Flandrin P, Millet C, Duvareille M, Fortrat JO, Gharib C (2002) Orthostatic tolerance and spontaneous baroreflex sensitivity in men versus women after 7 days of head-down bed rest. Auton Neurosci 100(1–2):66–76
D’Arcy Thompson (1917) On growth and form, 1st edn. Cambridge University Press, Cambridge
Damoulis PD, Hauschka PV (1997) Nitric oxide acts in conjunction with proinflammatory cytokines to promote cell death in osteoblasts. J Bone Miner Res 12:412–422
Dawson-Hughes B, Harris SS, Krall EA, Dallal GE (1997) Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older [see comments]. N Engl J Med 337:670–676
Dawson-Hughes B, Harris SS, Rasmussen H, Song L, Dallal GE (2004) Effect of dietary protein supplements on calcium excretion in healthy older men and women. J Clin Endocrinol Metab 89:1169–1173
DeRoshia CW, Greenleaf JE (2003) Performance and mood-state parameters during 30-day 6 degrees head-down bed rest with exercise training. J Clin Pharmacol 43:1235–1243
Delmas PD, Ensrud KE, Adachi JD, Harper KD, Sarkar S, Gennari C, Reginster JY, Pols HA, Recker RR, Harris ST, Wu W, Genant HK, Black DM, Eastell R (2002) Efficacy of raloxifene on vertebral fracture risk reduction in postmenopausal women with osteoporosis: four-year results from a randomized clinical trial. J Clin Endocrinol Metab 87:3609–3617
Delp MD, Colleran PN, Wilkerson MK, McCurdy MR, Muller-Delp J (2000) Structural and functional remodelling of skeletal muscle microvasculature is induced by simulated microgravity. Am J physiol Heart Circ Physiol 278:1866–1873
Dennis RA, Trappe TA, Simpson P, Carroll C, Huang BE, Nagarajan R, Bearden E, Gurley C, Duff GW, Evans WJ, Kornman K, Peterson CA (2004) Interleukin-1 polymorphisms are associated with the inflammatory response in human muscle to acute resistance exercise. J Physiol 560:617–626
Desplanches D (1997) Structural and functional adaptations of skeletal muscle to weightlessness. Int J Sports Med 18:259–264
Desplanches D, Hoppeler H, Mayet MH, Denis C, Claassen H, Ferretti G (1998) Effects of bedrest on deltoideus muscle morphology and enzymes. Acta Physiol Scand 162:135–140
Devine A, Dick IM, Islam AF, Dhaliwal SS, Prince RL (2005) Protein consumption is an important predictor of lower limb bone mass in elderly women. Am J Clin Nutr 81:1423–1428
Devogelaer JP, De Cooman S, Nagant dD (1992) Low bone mass in hypogonadal males: effect of testosterone substitution therapy, a densitometric study. Maturitas 15:17–23
di Prampero PE (1994) The twin bikes system for artificial gravity in space. J Gravit Physiol 1:12–14
di Prampero PE, Narici MV (2003) Muscles in microgravity: from fibres to human motion. J Biomech 36:403–412
di Prampero PE, Narici MV, Tesch PA (2001) Muscles in space. In: Fitton B, Battrick B (eds) A world without gravity. ESA Publications Division, ESA SP-1251, Noordwijk, pp 69–82
Dietrick JE, Whedon GD, Shorr E, Toscani V, Davis VB (1948) Effect of immobilization on metabolic and physiologic functions of normal men. Am J Med 4:3–35
Dijk DJ, Neri DF, Wyatt JK, Ronda JM, Riel E, Ritz-De Cecco A, Hughes RT, Elliott AR, Prisk GK, West JB (2001) Sleep, performance, circadian rhytms and light-dark cycles during two space shuttle flights. Am J Physiol 281:1647–1664
Donaldson DL, Hulley SB, Vogel JM, Hattner RS, Bayers JH, McMillan DE (1970) Effect of prolonged bed rest on bone mineral. Metabolism 19:1071–1084
Drummer C, Heer M, Baisch F, Blomqvist CG, Lang RE, Maass H, Gerzer R (1992) Diuresis and natriuresis following isotonic saline infusion in healthy young volunteers before, during, and after HDT. Acta Physiol Scand 604(Suppl):101–111
Drummer C, Heer M, Dressendorfer RA, Strasburger CJ, Gerzer R (1993) Reduced natriuresis during weightlessness. Clin Investig 71:678–686
Drummer C, Gerzer R, Baisch F, Heer M (2000a) Body fluid regulation in μ-gravity differs from Earth: an overview. Pflugers Arch 441:66–72
Drummer C, Heer M, Joosten M, Stormer I, Hesse C, Beck L, Wolfram G, Baisch F (2000b) Regulation and distribution of body fluid during a 6-day head-down tilt study in a randomized cross-over design. J Gravit Physiol 7:187–188
Eckberg DL, Fritsch JM (1991) Human autonomic responses to actual and simulated weightlessness. J Clin Pharmacol 31:888–892
Eckberg DL, Fritsch JM (1992) Influence of ten-day head-down bedrest on human carotid baroreceptor-cardiac reflex function. Acta Physiol Scand 604(Suppl):69–76
Elefteriou F, Ahn JD, Takeda S, Starbuck M, Yang X, Liu X, Kondo H, Richards WG, Bannon TW, Noda M, Clement K, Vaisse C, Karsenty G (2005) Leptin regulation of bone resorption by the sympathetic nervous system and CART. Nature 434:514–520
Ellis S, Kirby LC, Greenleaf JE (1993) Lower extremity muscle thickness during 30-day 6 degrees head-down bed rest with isotonic and isokinetic exercise training. Aviat Space Environ Med 64:1011–1015
Engelke KA, Doerr DF, Convertino VA (1995) A single bout of exhaustive exercise affects integrated baroreflex function after 16 days of head-down tilt. Am J physiol 269:641–620
Engelke KA, Doerr DF, Crandall CG, Convertino VA (1996) Application of Acute Maximal Exercise to Protect Orthostatic Tolerance after Simulated Microgravity. Am J Physiol 271:837–847
Eser P, Frotzler A, Zehnder Y, Knecht H, Denoth J, Schiessl H (2004) Relationship between the duration of paralysis and bone structure: a pQCT study of spinal cord injured individuals. Bone 34:869–880
Ferrando AA, Stuart CA, Brunder DG, Hillman GR (1995) Magnetic resonance imaging quantitation of changes in muscle volume during 7 days of strict bed rest. Aviat Space Environ Med 66:976–981
Ferrando AA, Lane HW, Stuart CA, Davis-Street J, Wolfe RR (1996) Prolonged bed rest decreases skeletal muscle and whole body protein synthesis. Am J Physiol 270E:627–633
Ferretti G, Antonutto G, Denis C, Hoppeler H, Minetti AE, Narici MV, Desplanches D (1997) The interplay of central and peripheral factors in limiting maximal O2 consumption in man after prolonged bed rest. Med Sci Sports Exerc 29:207–215
Ferretti G, Girardis M, Moia C, Antonutto G (1998) Effects of prolonged bed rest on cardiovascular oxygen transport during submaximal exercise in humans. Eur J Appl Physiol Occup Physiol 78:398–402
Ferretti G, Berg HE, Minetti AE, Moia C, Rampichini S, Narici MV (2001) Maximal instantaneous muscular power after prolonged bed rest in humans. J Appl Physiol 90:431–435
Ferretti G, Girardis M, Moia C, Antonutto G (2002) Effects of prolonged bed rest on cardiovascular oxygen transport during submaximal exercise in humans. J Gravit Physiol 9:67–68
Fettman MJ (2000) Dietary instead of pharmacological management to counter the adverse effects of physiological adaptations to space flight. Pflugers Arch 441:15–20
Finkelstein JS, Klibanski A, Neer RM, Doppelt SH, Rosenthal DI, Segre GV, Crowley WF Jr (1989) Increases in bone density during treatment of men with idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab 69:776–783
Fitts RH, Riley DR, Widrick JJ (2000) Physiology of a microgravity environment invited review: microgravity and skeletal muscle. J Appl Physiol 89:823–839
Fitts RH, Riley DR, Widrick JJ (2001) Functional and structural adaptations of skeletal muscle to microgravity. J Exp Biol 204:3201–3208
Foley CM, Mueller PJ, Hasser EM, Heesch CM (2005) Hindlimb unloading and female gender attenuate baroreflex mediated sympathoexcitation. Am J Physiol Regul Integr Comp Physiol 289:1440–1447
Folland J, Leach B, Little T, Hawker K, Myerson S, Montgomery H, Jones D (2000) Angiotensin-converting enzyme genotype affects the response of human skeletal muscle to functional overload. Exp Physiol 85:575–579
Fortney SM (1991) Development of lower body negative pressure as a countermeasure for orthostatic intolerance. J Clin Pharmacol 31:888–892
Fortney SM, Hyatt KH, Davis JE, Vogel JM (1991) Changes in body fluid compartments during a 28-day bed rest. Aviat Space Environ Med 62:97–104
Fortney SM, Turner C, Steinmann L, Driscoll T, Alfrey C (1994) Blood volume responses of men and women to bed rest. J Clin Pharmacol 34:434–439
Fortney SM, Schneider Victor S, Greenleaf John E (1996) The physiology of bed rest. In: Handbook of physiology, Chap. 39. Oxford University Press, New York, pp 889–939
Fortrat JO, Somody L, Gharib C (1998) Autonomic control of cardiovascular dynamics during weightlessness. Brain Res Rev 28:66–72
Fortrat JO, Sigaudo D, Hughson RL, Maillet A, Yamamoto Y, Gharib C (2001) Effect of prolonged head-down bed rest on complex cardiovascular dynamics. Auton Neurosci 86:192–201
Frings P, Baecker N, Boese A, Heer M (2005) High sodium chloride intake causes mild metabolic acidosis: is this the reason for increased bone resorption? FASEB J 19(5):1345
Fritsch JM, Charles JB, Bennett BS, Jones MM, Eckberg DL (1992) Short duration spaceflight impairs human carotid baroreceptor-cardiac reflex responses. J Appl Physiol 73:664–671
Frost HM (1987a) Bone “mass” and the “mechanostat”: a proposal. Anat Rec 219:1–9
Frost HM (1987b) The mechanostat: a proposed pathogenic mechanism of osteoporoses and the bone mass effects of mechanical and nonmechanical agents. Bone Miner 2:73–85
Frost HM (1990a) Skeletal structural adaptations to mechanical usage (SATMU): 1. Redefining Wolff’s law: the bone modeling problem. Anat Rec 226:403–413
Frost HM (1990b) Skeletal structural adaptations to mechanical usage (SATMU): 2. Redefining Wolff’s law: the remodeling problem. Anat Rec 226:414–422
Frost HM (2003) Bone’s mechanostat: a 2003 update. Anat Rec 275A:1081–1101
Frost HM, Schonau E (2000) The “muscle-bone unit” in children and adolescents: a 2000 overview. J Pediatr Endocrinol Metab 13:571–590
Funato K, Matsuo A, Yata H, Akima H, Suzuki Y, Gunji A, Fukunaga T (1997) Changes in force-velocity and power output of upper and lower extremity musculature in young subjects following 20 days bed rest. J Gravit Physiol 4:22–30
Gaffney FA, Buckey JC, Lane LD, Hillebrecht A, Schulz H, Meyer M, Baisch F, Beck L, Heer M, Maass H (1992) The effects of a 10-day period of head-down tilt on the cardiovascular responses to intravenous saline loading. Acta Physiol Scand 604(Suppl):121–130
Galilei G (1638) Discorsi e dimonstrazioni matematiche, intorno a due nuove scienze attentanti alla meccanica ed a movimenti locali. University of Wisconsin Press, Madison
Gallagher P, Trappe S, Harber M, Creer A, Mazzetti S, Trappe T, Alkner B, Tesch P (2005) Effects of 84-days of bedrest and resistance training on single muscle fibre myosin heavy chain distribution in human vastus lateralis and soleus muscles. Acta Physiol Scand 185:61–69
Gandia P, Bareille MP, Saivin S, Pavy-Le Traon A, Lavit M, Guell A, Houin G (2003) Influence of simulated weightlessness on the oral pharmacokinetics of acetaminophen as a gastric emptying probe in man: a plasma and a saliva study. J Clin Pharmacol 43:1235–1243
Garza C, Scrimshaw NS, Young VR (1977) Human protein requirements: a long-term metabolic nitrogen balance study in young men to evaulate the 1973 FAO/WHO safe level of egg protein intake. J Nutr 107:335–352
Gazenko OG, Kasyan II (1991) Pathogenesis and problems of efficacity of countermeasures in weightlessness In: Gazenko OG, Kasyan II (eds) Physiological Problems of Weightlessness. Medical Press, Moscow, pp 198–256
Germain P, Guell A, Marini JF (1995) Muscle strength during bedrest with and without muscle exercise as a countermeasure. Eur J Appl Physiol Occup Physiol 71:342–348
Gertz BJ, Clemens JD, Holland SD, Yuan W, Greenspan S (1998) Application of a new serum assay for type I collagen cross-linked N- telopeptides: assessment of diurnal changes in bone turnover with and without alendronate treatment. Calcif Tissue Int 63:102–106
Gharib C, Hughson RL (1992) Fluid and electrolyte regulation in space. Adv Space Biol Med 2:113–130
Gharib C, Gauquelin G, Pequignot JM, Geelen G, Bizollon CA, Guell A (1988) Early hormonal effects of head-down tilt (-10 degrees) in humans. Aviat Space Environ Med 59:624–629
Gharib C, Maillet A, Gauquelin G, Allevard AM, Guell A, Cartier R, Arbeille P (1992) Results of a 4-week head-down tilt with and without LBNP countermeasure: I. Volume regulating hormones. Aviat Space Environ Med 1:3–8
Ginty F (2003) Dietary protein and bone health. Proc Nutr Soc 62:867–876
Goebel G, Schweiger U, Kruger R, Fichter MM (1999) Predictors of bone mineral density in patients with eating disorders. Int J Eat Disord 25:143–150
Goldberger AL, Bungo MW, Baevsky RM, Bennett BS, Rigney DR, Mietus JE, Nikulina GA, Charles JB (1994a) Heart rate dynamics during long-term space flight: report on Mir cosmonauts. Am Heart J 128:202–204
Goldberger AL, Mietus JE, Rigney DR, Wood ML, Fortney SM (1994b) Effects of head-down bed rest on complex heart rate variability: response to LBNP testing. J Appl Physiol 77:2863–2869
Goodship AE, Lanyon LE, McFie H (1979) Functional adaptation of bone to increased stress. An experimental study. J Bone Joint Surg [Am] 61:539–546
Grant WB, Holick MF (2005) Benefits and requirements of vitamin D for optimal health: a review. Altern Med Rev 10:94–111
Greenleaf JE (1984) Physiology of fluid and electrolyte responses during inactivity: water immersion and bed rest. Med Sci Sports Exerc 16:20–25
Greenleaf JE (1997) Intensive exercise training during bed rest attenuates deconditioning. Med Sci Sports Exerc 29:191–196
Greenleaf JE, Bernauer EM, Ertl AC, Trowbridge TS, Wade CE (1989) Work capacity during 30 days of bed rest with isotonic and isokinetic exercise training. J Appl Physiol 67:1820–1826
Greenleaf JE, Vernikos J, Wade CE, Barnes PR (1992) Effect of leg exercise training on vascular volumes during 30 days of 6 degrees head-down bed rest. J Appl Physiol 72:1887–1894
Greenleaf JE, Bernauer EM, Ertl AC, Bulbulian R, Bond M (1994) Isokinetic strength and endurance during 30-day 6 degrees head-down bed rest with isotonic and isokinetic exercise training. Aviat Space Environ Med 65:45–50
Greenleaf JE, Gundo DP, Watenpaugh DE, Mulenburg GM, Marchman N, Looft-Wilson R, Hargens AR (1996) Cycle-powered short radius (1.9 m) centrifuge: exercise vs passive acceleration. J Gravit Physiol 3:61–62
Greenspan SL, Dresner-Pollak R, Parker RA, London D, Ferguson L (1997) Diurnal variation of bone mineral turnover in elderly men and women. Calcif Tissue Int 60:419–423
Greenleaf JE, Chou JL et al (1999) Short-arm (1.9 m) +2.2 Gz acceleration: isotonic exercise load-O2 uptake relationship. Aviat Space Environ Med 70:1173–1182
Greiwe JS, Cheng B, Rubin DC, Yarasheski KE, Semenkovich CF (2001) Resistance exercise decreases skeletal muscle tumor necrosis factor alpha in frail elderly humans. FASEB J 15:475–482
Grenon SM, Sheynberg N, Hurwitz S, Xiao G, Ramsdell CD, Ehrman MD, Mai CL, Kristjansson SR, Sundby GH, Cohen RJ, Williams GH (2004a) Renal, endocrine, and cardiovascular responses to bed rest in male subjects on a constant diet. J Investig Med 52:117–128
Grenon SM, Hurwitz S, Sheynberg N, Xiao X, Ramsdell CD, Mai CL, Cohen RJ, Williams GH (2004b) Role of individual predisposition in orthostatic intolerance before and after simulated microgravity. J Appl Physiol 96:1714–1722
Grenon SM, Xiao X, Hurwitz S, Ramsdell CD, Sheynberg N, Kim C, Williams GH, Cohen RJ (2005) Simulated microgravity induces microvolt T wave alternans. Ann Noninvasive Electrocardiol 10:363–370
Griffiths HJ, Bushueff B, Zimmermann RE (1976) Investigation of the loss of bone mineral in patients with spinal cord injury. Paraplegia 14:207–212
Grigoriev AI, Morukov BV, Oganov VS, Rakhmanov AS, Buravkova LB (1992) Effect of exercise and bisphosphonate on mineral balance and bone density during 360 day antiorthostatic hypokinesia. J Bone Miner Res 7:449–455
Guell A, Braak L, Le Traon AP, Gharib C (1991) Cardiovascular adaptation during simulated microgravity: lower body negative pressure to counter orthostatic hypotension. Aviat Space Environ Med 62:331–335
Gunga HC, Kirsch K, Baartz F, Maillet A, Gharib C, Nalishiti W, Rich I, Rocker L (1996) Erythropoietin under real and simulated microgravity conditions in humans. J Appl Physiol 81:761–773
Hannon R, Eastell R (2000) Preanalytical variability of biochemical markers of bone turnover. Osteoporos Int 11:30–44
Hara K, Akiyama Y, Nakamura T, Murota S, Morita I (1995) The inhibitory effect of vitamin K2 (menatetrenone) on bone resorption may be related to its side chain. Bone 16:179–184
Harm DL, Jennings RT, Meck JV, Powell MR, Putcha L, Sams CP, Schneider SM, Shackelford LC, Smith SM, Whitson PA (2001) Invited review: gender issues related to spaceflight: a NASA perspective. J Appl Physiol 91:2374–2383
Haruna Y, Suzuki Y, Kawakubo K, Gunji A (1994) Orthostatic tolerance and autonomous nervous functions before and after 20-days bed rest. Acta Physiol Scand 616(Suppl):71–81
Haruna Y, Bonde-Petersen F, Takenaka K, Suzuki Y, Kawakubo K, Gunji A (1997) Effects of the rennin-angiotensin-aldosterone system on the cardiovascular system during 20-days bed rest. J Gravit Physiol 4:62–68
Hasser EM, Moffitt JA (2001) Regulation of sympathetic nervous system function after cardiovascular deconditioning. Ann N Y Acad Sci 940:454–468
Hastreiter D, Young LR (1997) Effects of a gravity gradient on human cardiovascular responses. J Gravit Physiol 4:23–26
Hauschka PV, Lian JB, Cole DE, Gundberg CM (1989) Osteocalcin and matrix Gla protein: vitamin K-dependent proteins in bone. Physiol Rev 69:990–1047
Heer M (2002) Nutritional interventions related to bone turnover in European space missions and simulation models. Nutrition 18:853–856
Heer M, Drummer C, Baisch F, Maass H, Gerzer R, Kropp J, Blomqvist CG (1992) Effects of head-down tilt and saline loading on body weight, fluid, and electrolyte homeostasis in man. Acta Physiol Scand 604(Suppl):13–22
Heer M, Kamps N, Biener C, Korr C, Boerger A, Zittermann A, Stehle P, Drummer C (1999a) Calcium metabolism in microgravity. Eur J Med Res 4:357–360
Heer M, Baisch F, Kropp J, Gerzer R, Drummer C (2000) High dietary sodium chloride consumption may not induce body fluid retention in humans. Am J Physiol Renal Physiol 278:585–595
Heer M, De Santo NG, Cirillo M, Drummer C (2001a) Body mass changes, energy, and protein metabolism in space. Am J Kidney Dis 38:691–695
Heer M, Elia M, Ritz P (2001b) Energy and fluid metabolism in microgravity. Curr Opin Clin Nutr Metab Care 4:307–311
Heer M, Mika C, Grzella I, Drummer C, Herpertz-Dahlmann B (2002) Changes in bone turnover in patients with anorexia nervosa during eleven weeks of inpatient dietary treatment. Clin Chem 48:754–760
Heer M, Boese A, Baecker N, Smith SM High (2004a) Calcium intake during bed rest does not counteract disuse-induced bone loss. FASEB J 18:573–576
Heer M, Boese A, Baecker N, Zittermann A, Smith SM (2004b) Moderate hypocaloric nutrition does not exacerbate bone resorption during bed rest. FASEB J 18:478–484
Hinghofer-Szalkay H, Rossler A, Scharfetter H, Pliz K, Laszlo Z (2002a) Fluid volume changes and LBNP response after simulated weightlessness with varied oral sodium supply. J Gravit Physiol 9:99–100
Hinghofer-Szalkay HG, Laszlo Z, Jezova D, Rossler A, Haditsch B, Pilz K, Passath H, Shrfetter H (2002b) Bed rest immobilization with various oral sodium supply: plasma hormones and body fluids. Endocr Regul 36:151–9
Hirayanagi K, Iwase S, Kamiya A, Sasaki T, Mano T, Yajima K (2004) Functional changes in autonomic nervous system and baroreceptor reflex induced by 14 days of 6 degrees head-down bed rest. Eur J Appl Physiol 92:160–167
Hotta M, Shibasaki T, Sato K, Demura H (1998) The importance of body weight history in the occurrence and recovery of osteoporosis in patients with anorexia nervosa: evaluation by dual X- ray absorptiometry and bone metabolic markers. Eur J Endocrinol 139:276–283
Hughson RL, Yamamoto Y, Maillet A, Fortrat JO, Pavy-Le Traon A, Butler GC, Guell A, Gharib C (1994) Altered autonomic regulation of cardiac function during head-up tilt after 28-day head-down bed-rest with counter-measures. Aviat Space Environ Med 65:293–300
Hughson RL, Yamamoto Y, Blaber AP, Maillet A, Fortrat JO, Pavy-LeTraon A, Marini JF, Guell A, Gharib C (1998) Effect of 28-day head-down bed rest with countermeasures on heart rate variability during LBNP. Eur J Appl Physiol Occup Physiol 77:50–59
Ihle R, Loucks AB (2004) Dose-response relationships between energy availability and bone turnover in young exercising women. J Bone Miner Res 19:1231–1240
Ilich JZ, Kerstetter JE (2000) Nutrition in bone health revisited: a story beyond calcium. J Am Coll Nutr 19:715–737
Inoue M, Tanaka H, Moriwake T, Oka M, Sekiguchi C, Seino Y (2000) Altered biochemical markers of bone turnover in humans during 120 days of bed rest. Bone 26:281–286
Ishizaki Y, Fukuoka H, Katsura T, Nishimura Y, Kiriyama M, Higurashi M, Suzuki Y, Kawakubo K, Gunji A (1994) Psychological effects of bed rest in young healthy subjects. Acta Physiol Scand 616:83–87
Ishizaki Y, Fukuoka H, Ishizaki T, Katsura T, Nishimura Y, Haruna M, Suzuki Y, Kawakubo K, Gunji A (1997) Psychological stress induced by 20 days bed rest. J Gravit Physiol 4:95–98
Ishizaki Y, Ishizaki T, Fukuoka H, Kim CS, Fujita M, Maegawa Y, Fujioka H, Katsura T, Suzuki Y, Gunji A (2002) Changes in mood status and neurotic levels during a 20-day bed rest. Acta Astronaut 50:453–459
Ishizaki Y, Fukuoka H, Ishizaki T, Tanaka H, Ishitobi H (2004) The implementation of game in a 20-day head-down tilting bed rest experiment upon mood status and neurotic levels of rest subjects. Acta Astronaut 55:945–952
Ito M, Matsumoto T, Enomoto H, Tsurusaki K, Hayashi K (1999) Effect of nonweight bearing on tibial bone density measured by QCT in patients with hip surgery. J Bone Miner Metab 17:45–50
Ivanova SM, Labetskaia OI, Iarlykova IV, Shishkanova ZG, Barsel’ VA, Bashkatova VG, Kogan IG (1997a) The effect of head-down tilt bed rest on metabolism of erythrocytes and functional state of membranes in females. Aviakosm Ekolog Med 31:58–62
Ivanova SM, Levina AA, Novoderzhkina IK, Sarycheva TG, Belozerova IN, Tsybul’skaia MM, Karashtin VV, Morukov BV, Kozinets GI (1997b) Dynamics of the hematological shifts in females during antiorthostatic hypokinesia. Aviakosm Ekolog Med 31:52–57
Iwasaki KI, Hirayanagi K, Sasaki T, Kinoue T, Ito M, Miyamoto A, Igarashi M, Yajima K (1998) Effects of repeated long duration +2 Gz load on man’s cardiovascular function. Acta Astronaut 42:175–183
Iwasaki KI, Zhang R, Zuckerman JH, Pawelczyk JA, Levine BD (2000) Effect of head-down-tilt bed rest and hypovolemia on dynamic regulation of heart rate and blood pressure. Am J Physiol Regul Integr Comp Physiol 279:2189–2199
Iwasaki KI, Sasaki T et al (2001) Usefulness of daily +2 Gz load as a countermeasure against physiological problems during weightlessness. Acta Astronaut 49:227–235
Iwasaki K, Zhang R, Perhonen MA, Zuckerman JH, Levine BD (2004) Reduced baroreflex control of heart period after bed rest is normalized by acute plasma volume restoration. Am J Physiol Regul Integr Comp Physiol 287:1256–1262
Jarvinen TL, Sievanen H, Kannus P, Jarvinen M (1998) Dual-energy X-ray absorptiometry in predicting mechanical characteristics of rat femur. Bone 22:551–558
Johansen LB, Gharib C, Allevard AM, Sigaudo D, Christensen NJ, Drummer C, Norsk P (1997) Haematocrit, plasma volume and noradrenaline in humans during simulated weightlessness for 42 days. Clin Physiol 17:203–210
Jorgensen L, Crabtree NJ, Reeve J, Jacobsen BK (2000) Ambulatory level and asymmetrical weight bearing after stroke affects bone loss in the upper and lower part of the femoral neck differently: bone adaptation after decreased mechanical loading. Bone 27:701–707
Kameda T, Miyazawa K, Mori Y, Yuasa T, Shiokawa M, Nakamaru Y, Mano H, Hakeda Y, Kameda A, Kumegawa M (1996) Vitamin K2 inhibits osteoclastic bone resorption by inducing osteoclast apoptosis. Biochem Biophys Res Commun 220:515–519
Kamiya A, Michikami D, Fu Q, Iwase S, Mano T (1999a) Vasomotor sympathetic nerve responses to static handgrip after simulated microgravity. J Gravit Physiol 6:153–154
Kamiya A, Iwase S, Kitazawa H, Mano T (1999b) Muscle sympathetic nerve activity (MSNA) after 120 days of 6 degrees head-down bed rest (HDBR). Environ Med 43:150–152
Kamiya A, Michikami D, Fu Q, Iwase S, Mano T (1999c) Sympathetic vasoconstriction and orthostatic intolerance after simulated microgravity. J Gravit Physiol 6:101–102
Kamiya A, Iwase S, Kitazawa H, Mano T, Vinogradova OL, Kharchenko IB (2000) Baroreflex control of muscle sympathetic nerve activity after 120 days of 6 degrees head-down bed rest. Am J Physiol Regul Integr Comp Physiol 278:445–452
Kamiya A, Michikami D, Fu Q, Iwase S, Hayano J, Kawada T, Mano T, Sunagawa K (2003) Pathophysiology of orthostatic hypotension after bed rest: paradoxical sympathetic withdrawal. Am J Physiol Heart Circ Physiol 285:1158–1167
Kamiya A, Michikami D, Iwase S, Hayano J, Kawada T, Sugimachi M, Sunagawa K (2004) Alpha-adrenergic vascular responsiveness to sympathetic nerve activity is intact after head-down bed rest in humans. Am J Physiol Regul Integr Comp Physiol 286:151–157
Kawai Y, Murthy G, Watenpaugh DE, Breit GA, Deroshin CW, Hargens AR (1993) Cerebral blood flow velocity in humans exposed to 24 h of head-down tilt. J Apply Physiol 74:3046–3051
Kawakami Y, Muraoka Y, Kubo K, Suzuki Y, Fukunaga T (2000) Changes in muscle size and architecture following 20 days of bed rest. J Gravit Physiol 7:53–59
Kawakami Y, Akima H, Kubo K, Muraoka Y, Hasegawa H, Kouzaki M, Imai M, Suzuki Y, Gunji A, Kanehisa H, Fukunaga T (2001) Changes in muscle size, architecture, and neural activation after 20 days of bed rest with and without resistance exercise. Eur J Appl Physiol 84:7–12
Kawashima S, Akima H, Kuno SY, Gunji A, Fukunaga T (2004) Human adductor muscles atrophy after short duration of unweighting. Eur J Appl Physiol 92:602–605
Khan MH, Kunselman AR, Leuenberger UA, Davidson WR Jr, Ray CA, Gray KS, Hogeman CS, Sinoway LI (2002) Attenuated sympathetic nerve responses after 24 hours of bed rest. Am J Physiol Heart Circ Physiol 282:2210–2215
Kim H, Iwasaki K, Miyake T, Shiozawa T, Nozaki S, Yajima K (2003) Changes in bone turnover markers during 14-day 6 degrees head-down bed rest. J Bone Miner Metab 21:311–315
Kimmerly DS, Shoemaker JK (2002) Hypovolemia and neurovascular control during orthostatic stress. Am J Physiol Heart Circ Physiol 282:645–655
Kiselev RK, Chayka AM, legenkov VI (1986) Effect of coamide and folicobalamin on erythropoiesis under normal living conditions and during antiorthostatic hypokinesia. Kosm Biol Aviakosm Med 20:48–53
Klein-Nulend J, Bacabac RG, Veldhuijzen JP, Van Loon JJ (2003) Microgravity and bone cell mechanosensitivity. Adv Space Res 32:1551–1559
Knapen MH, Hamulyak K, Vermeer C (1989) The effect of vitamin K supplementation on circulating osteocalcin (bone Gla protein) and urinary calcium excretion. Ann Intern Med 111:1001–1005
Knapen MH, Jie KS, Hamulyak K, Vermeer C (1993) Vitamin K-induced changes in markers for osteoblast activity and urinary calcium loss. Calcif Tissue Int 53:81–85
Koryak YA (1998a) Effect of 120 days of bed-rest with and without countermeasures on the mechanical properties of the triceps surae muscle in young women. Eur J Appl Physiol Occup Physiol 78:128–135
Koryak YA (1998b) Influence of 120-days 6 degrees head-down tilt bed rest on the functional properties of the neuromuscular system in man. Aviat Space Environ Med 69:766–770
Kozlovskaya IB, Grigoriev AI et al (1995) Countermeasure of the negative effects of weightlessness on physical systems in long-term space flights. Acta Astronaut 36:661–668
Krebs JM, Schneider VS, LeBlanc AD (1988) Zinc, copper, and nitrogen balances during bed rest and fluoride supplementation in healthy adult males. Am J Clin Nutr 47:509–514
Krebs JM, Schneider VS, Leblanc AD, Kuo MC, Spector E, Lane HW (1993) Zinc and copper balances in healthy adult males during and after 17 wk of bed rest. Am J Clin Nutr 58:897–901
Krieger NS, Sessler NE, Bushinsky DA (1992) Acidosis inhibits osteoblastic and stimulates osteoclastic activity in vitro. Am J Physiol 262:442–448
Krishnan SS, Harrison JE, Strauss A, Mukherjee S, Muller C (1993) In vitro accuracy and reproducibility of bone and soft tissue measurements by DXA. Basic Life Sci 60:329–330
Kubo K, Akima H, Ushiyama J, Tabata I, Fukuoka H, Kanehisa H, Fukunaga T (2004a) Effects of 20 days of bed rest on the viscoelastic properties of tendon structures in lower limb muscles. Br J Sports Med 38:324–330
Kubo K, Akima H, Ushiyama J, Tabata I, Fukuoka H, Kanehisa H, Fukunaga T (2004b) Effects of resistance training during bed rest on the viscoelastic properties of tendon structures in the lower limb. Scand J Med Sci Sports 14:296–302
Lambertz D, Perot C, Kapranski R, Goubel F (2001) Effects of long-term spaceflight on mechanical properties of muscles in humans. J Appl Physiol 90:179–188
Lampe L, Wienhold K, Meyer G, Baisch F, Maass H, Hollmann W, Rost R (1992) Effects of simulated microgravity (HDT) on blood fluidity. J Appl Physiol 73(4):1366–1369
Larsson L, Li X, Berg HE, Frontera WR (1996) Effects of removal of weight-bearing function on contractility and myosin isoform composition in single human skeletal muscle cells. Pflugers Arch 432:320–328
Lathers CM, Charles JB (1994) Orthostatic hypotension in patients, bed rest subjects, and astronauts. J Clin Pharmacol 34:403–417
Lau EM, Woo J (1998) Nutrition and osteoporosis. Curr Opin Rheumatol 10:368–372
LeBlanc A, Schneider V, Krebs J, Evans H, Jhingran S, Johnson P (1987) Spinal bone mineral after 5 weeks of bed rest. Calcif Tissue Int 41:259–261
LeBlanc A, Schneider VS, Evans HJ, Engelbretson DA, Krebs JM (1990) Bone mineral loss and recovery after 17 weeks of bed rest. J Bone Miner Res 5:843–850
LeBlanc AD, Schneider VS, Evans HJ, Pientok C, Rowe R, Spector E (1992) Regional changes in muscle mass following 17 weeks of bed rest. J Appl Physiol 73:2172–2178
LeBlanc A, Schneider V, Shakelford L, West S, Oganov V, Bakulin A, Varonin L (2000) Bone mineral and lean tissue loss after long duration space flight. J Musculoskelet Neuron Interact 1:157–160
LeBlanc AD, Driscol TB, Shackelford LC, Evans HJ, Rianon NJ, Smith SM, Feeback DL, Lai D (2002) Alendronate as an effective countermeasure to disuse induced bone loss. J Musculoskelet Neuronal Interact 2:335–343
Leach CS, Alfrey CP, Suki WN, Leonard JI, Rambaut PC, Inners LD, Smith SM, Lane HW, Krauhs JM (1996) Regulation of body fluid compartments during short-term spaceflight. J Appl Physiol 8:105–116
Lee SM, Bennett BS, Hargens AR, Watenpaugh DE, Ballard RE, Murthy G, Ford SR, Fortney SM (1997) Upright exercise or supine lower body negative pressure exercise maintains exercise responses after bed rest. Med Sci Sports Exerc 29:892–900
Lee SM, Williams WJ, Schneider SM (2002) Role of skin blood flow and sweating rate in exercise thermoregulation after bed rest. J Appl Physiol 9:2026–2034
Lennkh C, de Zwaan M, Bailer U, Strnad A, Nagy C, el-Giamal N, Wiesnagrotzki S, Vytiska E, Huber J, Kasper S (1999) Osteopenia in anorexia nervosa: specific mechanisms of bone loss. J Psychiatr Res 33:349–356
Leppala J, Kannus P, Natri A, Pasanen M, Sievanen H, Vuori I, Jarvinen M (1999) Effect of anterior cruciate ligament injury of the knee on bone mineral density of the spine and affected lower extremity: a prospective one-year follow-up study. Calcif Tissue Int 64:357–363
Levine BD, Zuckerman JH, Pawelczyk JA (1997) Cardiac atrophy after bed-rest deconditioning: a nonneural mechanism for orthostatic intolerance. Circulation 96:517–525
Lindberg MK, Vandenput L, Moverare SS, Vanderschueren D, Boonen S, Bouillon R, Ohlsson C (2005) Androgens and the skeleton. Minerva Endocrinol 30:15–25
Linnarsson D, Spaak J, Sundblad P (2006) Baroreflex impairment during rapid posture changes at rest and exercise after 120 days of bed rest. Eur J Appl Physiol 96:37–45
Lobachik VI, Zhidkov VV, Abrosimov SV (1989) Body fluid status during a 120-day period of hypokinesis with head-down tilt. Kosm Biol Aviakosm Med 23:57–61
Lochmuller EM, Eckstein F, Kaiser D, Zeller JB, Landgraf J, Putz R, Steldinger R (1998) Prediction of vertebral failure loads from spinal and femoral dual-energy X-ray absorptiometry, and calcaneal ultrasound: an in situ analysis with intact soft tissues. Bone 23:417–424
Loeppky JA, Roach RC, Selland MA, Scotto P, Greene ER, Luft UC (1993) Effects of prolonged head-down bed rest on physiological responses to moderate hypoxia. Aviat Space Environ Med 64:275–286
Louisy F, Berry P, Marini JF, Guell A, Guezennec CY (1995a) Characteristics of the venous hemodynamics of the leg under simulated weightlessness: effects of physical exercise as countermeasure. Aviat Space Environ Med 66:542–549
Louisy F, Schroiff P, Guezennec CY, Guell A (1995b) Leg venous hemodynamics and leg volumes during a 42 day-6 degrees head-down bedrest. Acta Astronaut 36:575–579
Louisy F, Schroiff P, Guell A (1997) Changes in leg vein filling emptying characteristics and leg volumes during long-term head-down bed rest. J Appl Physiol 82:1726–1733
Lu LL, Zhong CF, Yang JS, Tao Y, Zhao GX (2000) Effects of 30 degrees head down tilt on lung function. Space Med Med Eng (Beijing) 13:187–190
Ludwig DA, Convertino VA (1994) Predicting orthostatic intolerance: physics or physiology? Aviat Space Environ Med 65:404–411
Ludwig DA, Vernikos J, Wade CE, Convertino VA (2001) Blood pressure changes during orthostatic stress: evidence of gender differences in neuroeffector distribution. Aviat Space Environ Med 72:892–898
Lueken SA, Arnaud SB, Taylor AK, Baylink DJ (1993) Changes in markers of bone formation and resorption in a bed rest model of weightlessness. J Bone Miner Res 8:1433–1438
Maass H, Transmontano J, Baisch F (1992) Response of adrenergic receptors to 10 days head-down tilt bedrest. Acta Physiol Scand 604(Suppl):61–68
Machinskii GV, Buzulina VP, Mikhailov VM, Nechaeva EI (1987) Functional status of the human cardiorespiratory system after 30 hours’ antiorthostatic hypokinesia. Kosm Biol Aviakosm Med 21:46–48
Maganaris CN, Reeves ND, Rittweger J, Sargeant AJ, Jones DA, Gerrits K, De Haan A (2006) Adaptive response of human tendon to paralysis. Muscle Nerve 33:85–92
Maillet A, Pavy-Le Traon A, Allevard AM, Sigaudo D, Hughson RL, Gharib C, Gauquelin G (1994) Hormone changes induced by 37.5-h head-down tilt (-6°). J Appl Physiol 68:497–503
Maillet A, Gauquelin G, Gunga HC, Fortrat JO, Kirsch K, Guell A, Bizollon ChA, Gharib C (1995) Blood volume regulating hormones response during two space related simulation protocols: four-week confinement and head-down bed-rest. Acta Astronaut 35:547–552
Maillet A, Fagette S, Allevard AM, Pavy-Le Traon A, Guell A, Gharib C, Gauquelin G (1996) Cardiovascular and hormonal response during a 4-week head-down tilt with and without exercise and LBNP countermeasures. J Gravit Physiol 3:37–48
Maillet A, Zaouli-Ajina M, Vorobiev D, Blanc S, Pastouchkova L, Reushkina G, Morukov B, Grigoriev AI, Gharib C, Gauquelin-Koch G (2000) Orthostatic tolerance and hormonal changes in women during 120 days of head-down bed rest. Aviat Space Environ Med 71:706–714
Maimoun L, Couret I, Micallef JP, Peruchon E, Mariano-Goulart D, Rossi M, Leroux JL, Ohanna F (2002) Use of bone biochemical markers with dual-energy x-ray absorptiometry for early determination of bone loss in persons with spinal cord injury. Metabolism 51:958–963
Martini LA, Cuppari L, Colugnati FA, Sigulem DM, Szejnfeld VL, Schor N, Heilberg IP (2000) High sodium chloride intake is associated with low bone density in calcium stone-forming patients. Clin Nephrol 54:85–93
Martin DE, Severns AE, Kabo JM (2004) Determination of mechanical stiffness of bone by pQCT measurements: correlation with non-destructive mechanical four-point bending test data. J Biomech 37:1289–1293
McGarry JG, Klein-Nulend J, Mullender MG, Prendergast PJ (2005) A comparison of strain and fluid shear stress in stimulating bone cell responses: a computational and experimental study. FASEB J 19:482–484
Meck JV, Waters WW, Ziegler MG, deBlock HF, Mills PJ, Robertson D, Huang PL (2004) Mechanisms of postspaceflight orthostatic hypotension: low alpha1-adrenergic receptor responses before flight and central autonomic dysregulation postflight. Am J Physiol Heart Circ Physiol 286:1486–1495
Mikines KJ, Dela F, Tronier B, Galbo H (1989) Effect of 7 days of bed rest on dose-response relation between plasma glucose and insulin secretion. Am J Physiol 257:43–48
Mikines KJ, Richter EA, Dela F, Galbo H (1991) Seven days of bed rest decrease insulin action on glucose uptake in leg and whole body. J Appl Physiol 70:1245–1254
Millet C, Custaud MA, Maillet A, Allevard AM, Duvareille M, Gauquelin-Koch G, Gharib C, Fortrat JO (2001) Endocrine responses to 7 days of head-down bed rest and orthostatic tests in men and women. Clin Physiol 21:172–183
Monk TH, Kennedy SK, Rose LR, Linenger JM (2001) Decreased human Circadian Pacemaker influence after 100 days in space: a case study. Psychsomatic Med 63:881–885
Montgomery LD (1993) Body volume changes during simulated microgravity I: technique and comparison of men and women during horizontal bed rest. Aviat Space Environ Med 64(10):893–898
Montmerle S, Spaak J, Linnarsson D (2002) Lung function during and after prolonged head-down bed rest. J Appl Physiol 92:75–83
Moore TP, Thornton WE (1987) Space shuttle inflight and postflight fluid shifts measured by leg volume changes. Aviat Space Environ Med 58:91–96
Moore AD Jr, Lee SM, Charles JB, Greenisen MC, Schneider SM (2001) Maximal exercise as a countermeasure to orthostatic intolerance after spaceflight. Med Sci Sports Exerc 33:75–80
Mtinangi BL, Hainsworth R (1999) Effects of moderate exercise training on plasma volume, baroreceptor sensitivity and orthostatic tolerance in healthy subjects. Exp Physiol 84:121–130
Murthy G, Watenpaugh DE, Ballard RE, Hargens AR (1994) Supine exercise during lower body negative pressure effectively simulates upright exercise in normal gravity. J Appl Physiol 76:2742–2748
Narici MV, Roi GS, Landoni L, Minetti AE, Cerretelli P (1989) Changes in force, cross-sectional area and neural activation during strength training and detraining of the human quadriceps. Eur J Appl Physiol Occup Physiol 59(4):310–319
Narici M, Kayser B, Barattini P, Cerretelli P (2003) Effects of 17-day spaceflight on electrically evoked torque and cross-sectional area of the human triceps surae. Eur J Appl Physiol 90:275–282
Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, Hodsman AB, Eriksen EF, Ish-Shalom S, Genant HK, Wang O, Mitlak BH (2001) Effect of parathyroid hormone (1–34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 344:1434–1441
Nicogossian AE et al (1994) Space physiology and medicine, 3rd edn. Lea & Febiger A Waverly, Philadelphia
Nishimura Y, Fukuoka H, Kiriyama M, Suzuki Y, Oyama K, Ikawa S, Higurashi M, Gunji A (1994) Bone turnover and calcium metabolism during 20 days bed rest in young healthy males and females. Acta Physiol Scand 616(Suppl):27–35
Nordin BE, Need AG, Morris HA, Horowitz M (1993) The nature and significance of the relationship between urinary sodium and urinary calcium in women. J Nutr 123:1615–1622
Nordin BE, Need AG, Steurer T, Morris HA, Chatterton BE, Horowitz M (1998) Nutrition, osteoporosis, and aging. Ann N Y Acad Sci 854:336–351
Norsk P (1997) Gravitational stress and fluid volume regulation: a suggestion for revision of current hypotheses. J Gravit Physiol 4:85–88
Norsk P (2005a) Cardiovascular and fluid volume control in humans in space. Curr pharm Biotechnol 6:325–330
Norsk P, Christensen NJ, Vorobiev D, Suzuki Y, Drummer C, Heer M (1998) Effects of head-down bed rest and microgravity on renal fluid excretion. J Gravit Physiol 5:81–84
Oganov VS, Grigor’ev AI, Voronin LI, Rakhmanov AS, Bakulin AV, Schneider VS, LeBlanc AD (1992) Bone mineral density in cosmonauts after flights lasting 4.5–6 months on the Mir orbital station. Aviakosm Ekolog Med 26:20–24
Ohira Y, Jiang B, Roy RR, Oganov V, Ilyina-Kakueva E, Marini JF, Edgerton VR (1992) Rat soleus muscle fiber responses to 14 days of spaceflight and hindlimb suspension. J Appl Physiol 73:51–57
Ohira Y, Yoshinaga T, Ohara M, Nonaka I, Yoshioka T, Yamashita-Goto K, Shenkman BS, Kozlovskaya IB, Roy RR, Edgerton VR (1999) Myonuclear domain and myosin phenotype in human soleus after bed rest with or without loading. J Appl Physiol 87:1776–1785
Ohira Y, Yoshinaga T, Nonaka I, Ohara M, Yoshioka T, Yamashita-Goto K, Izumi R, Yasukawa K, Sekiguchi C, Shenkman BS, Kozzlovskaya IB (2000) Histochemical responses of human soleus muscle fibers to long-term bedrest with or without countermeasures. Jpn Physiol 50:41–47
Özkaya N, Nordin M (1998) Fundamentals of Biomechanics. Springer, New York
Paddon-Jones D, Sheffield-Moore M, Urban RJ, Sanford AP, Aarsland A, Wolfe RR, Ferrando AA (2004a) Essential amino acid and carbohydrate supplementation ameliorates muscle protein loss in humans during 28 days bedrest. J Clin Endocrinol Metab 89:4351–4358
Pannier BM, Lacolley PJ, Gharib C, London GM, Cuche JL, Duchier JL, Levy BI, Safar ME (1991) Twenty-four hours of bed rest with head-down tilt: venous and arteriolar changes of limbs. Am J Physiol 260:1043–1050
Pavy-Le Traon A, Rous de Feneyrol A, Cornac A, Abdeseelam R, N’Guyen D, Lazerges M, Guell A, Bes A (1994) Psychomotor performance during a 28 day head-down tilt with and without lower body negative pressure. Acta Astronaut 4:319–330
Pavy-Le Traon A, Vasseur P, Arbeille P, Guell A, Bes A, Gharib C (1995) Effects of 28-day head-down tilt with and without counter-measure on lower body negative pressure responses. Aviat Space Environ Med 66:982–991
Pavy-Le Traon A, Allevard AM, Fortrat JO, Vasseur P, Gauquelin G, Guell A, Bes A, Gharib C (1997a) Cardiovascular and hormonal changes induced by a simulation of a lunar mission. Aviat Space Environ Med 68:829–837
Pavy-Le Traon A, Sigaudo D, Vasseur P, Fortrat JO, Guell A, Hughson RL, Gharib C (1997b) Orthostatic tests after a 4-day confinement or simulated weightlessness. Clin Physiol 17:41–55
Pavy-Le Traon A, Sigaudo D, Vasseur P, Maillet A, Fortrat JO, Hughson RL, Gauquelin-Koch G, Gharib C (1998) Cardiovascular reponses to orthostatic tests after a 42-day head-down bed-rest. Eur J Appl Physiol 77:50–59
Pavy-Le Traon A, Louisy F, Vasseur-Clausen P, Guell A, Gharib C (1999) Contributory factors to orthostatic intolerance after simulated weightlessness. Clin Physiol 19:360–368
Pavy-Le Traon A, Maillet A, Vasseur Clausen P, Custaud MA, Alferova I, Gharib C, Fortrat JO (2001) Clinical effects of thigh cuffs during a 7-day 6 degrees head-down bed rest. Acta Astronaut 49:145–151
Pavy-Le Traon A, Costes-Salon MC, Vasseur-Clausen P, Bareille MP, Maillet A, Parant M (2002) Changes in kinetics of cerebral auto-regulation with head-down bed rest. Clin Physiol Funct Imaging 22:108–114
Pavy-Le Traon A, Curnier D, Bernard J, Beroud S, Costes-Salon MC, Galinier M (2005) Effects of prolonged head down bed rest with and without Flywheel exercise on heart rate variability and ventricular repolarisation. J Gravit Physiol 12:79–80
Pawelczyk JA, Zuckerman JH, Blomqvist CG, Levine BD (2001) Regulation of muscle sympathetic nerve activity after bed rest deconditioning. Am J Physiol Heart Circ Physiol 280:2230–2239
Pawlak W, Kedziora J, Zolynski K, Kedziora-Kornatowska K, Blaszczyk J, Witkowski P, Zieleniewski J (1998) Effect of long term bed rest in men on enzymatic antioxidative defence and lipid peroxidation in erythrocytes. J Gravit Physiol 5:163–164
Perhonen MA, Zuckerman JH, Levine BD (2001) Deterioration of left ventricular chamber performance after bed rest: “cardiovascular deconditioning” or hypovolemia? Circulation 103:1851–1857
Platts SH, Ziegler MG, Waters WW, Mitchell BM, Meck JV (2004) Midodrine prescribed to improve recurrent post-spaceflight orthostatic hypotension Am J Physiol regul Integr Comp Physiol 75(6):554–556; 286:151–57
Ploutz-Snyder LL, Tesch PA, Crittenden DJ, Dudley GA (1995) Effect of unweighting on skeletal muscle use during exercise. J Appl Physiol 79:168–175
Portero P, Vanhoutte C, Goubel F (1996) Surface electromyogram power spectrum changes in human leg muscles following 4 weeks of simulated microgravity. Eur J Appl Physiol Occup Physiol 73:340–345
Prentice A (2001) The relative contribution of diet and genotype to bone development. Proc Nutr Soc 60:45–52
Prentice A (2004) Diet, nutrition and the prevention of osteoporosis. Public Health Nutr 7:227–243
Prisby RD, Nelson AG, Latsch E (2004) Eccentric exercise prior to hindlimb unloading attenuated reloading muscle damage in rats. Aviat Space Environ Med 75:941–946
Prou E, Marini JF (1997) Muscle research in space–increased muscle susceptibility to exercise-induced damage after a prolonged bedrest. Int J Sports Med 18:317–320
Ralston SH (1997) The Michael Mason Prize Essay 1997. Nitric oxide and bone: what a gas! Br J Rheumatol 36:831–838
Ramsdell CD, Mullen TJ, Sundby GH, Rostoft S, Sheynberg N, Aljuri N, Maa M, Mukkamala R, Sherman D, Toska K, Yelle J, Bloomfield D, Williams GH, Cohen RJ (2001) Midodrine prevents orthostatic intolerance associated with simulated spaceflight. J Appl Physiol 90:2245–2248
Raven PB (1993) An overview of the problem: exercise training and orthostatic intolerance. Med Sci Sports Exerc 25:702–704
Raven PB, Pawelczyk JA (1993) Chronic endurance exercise training: a condition of inadequate blood pressure regulation and reduced tolerance to LBNP. Med Sci Sports Exerc 25:713–721
Reddy ST, Wang CY, Sakhaee K, Brinkley L, Pak CY (2002) Effect of low-carbohydrate high-protein diets on acid-base balance, stone-forming propensity, and calcium metabolism. Am J Kidney Dis 40:265–274
Reeves NJ, Maganaris CN, Ferretti G, Narici MV (2002) Influence of simulated microgravity on human skeletal muscle architecture and function. J Gravit Physiol 9:153–154
Reeves ND, Maganaris CN, Ferretti G, Narici MV (2005) Influence of 90-day simulated microgravity on human tendon mechanical properties and the effect of resistive countermeasures. J Appl Physiol 98:2278–2286
Regnard J, Heer M, Drummer C, Norsk P (2001) Validity of microgravity simulation models on earth. Am J Kidney Dis 38:668–674
Ricci TA, Chowdhury HA, Heymsfield SB, Stahl T, Pierson RN Jr, Shapses SA (1998) Calcium supplementation suppresses bone turnover during weight reduction in postmenopausal women. J Bone Miner Res 13:1045–1050
Rink L, Gabriel P (2000) Zinc and the immune system. Proc Nutr Soc 59:541–552
Rittweger J, Felsenberg D (2004) Resistive vibration exercise prevents bone loss during 8 weeks of strict bed rest in healthy male subjects: Results from the Berlin BedRest (BBR) study. J Bone Miner Res 19:1145
Rittweger J, Frost HM, Schiessl H, Ohshima H, Alkner B, Tesch P, Felsenberg D (2005) Muscle atrophy and bone loss after 90 days’ bed rest and the effects of flywheel resistive exercise and pamidronate: results from the LTBR study. Bone 36:1019–1029
Rittweger J, Hunek P, Gast U, Belavy D, Boerst H, Armbrecht G, Mulder E, Schubert H, de Haan A, Stegeman DF, Felsenberg D (2006) The Berlin BedRest study: maintenance of a highly demanding resistive exercise program during 56 days of strict bed rest. Int J Sports Med 27:553–559
Robbe HW, Mulder LJ, Ruddel H, Langewitz WA, Veldman JB, Mulder G (1987) Assessment of baroreceptor reflex sensitivity by means of spectral analysis. Hypertension 10:538–543
Roumy J, Diridillou S, Herault S, Fomina G, Alferova I, Arbeille P (2001) Effect of the thigh-cuffs on the carotid artery diameter jugular vein section and facial skin edema: HDT study. Acta Astronaut 49:153–159
Roux C, Reginster JY, Fechtenbaum J, Kolta S, Sawicki A, Tulassay Z, Luisetto G, Padrino JM, Doyle D, Prince R, Fardellone P, Sorensen OH, Meunier PJ (2006) Vertebral fracture risk reduction with strontium ranelate in women with postmenopausal osteoporosis is independent of baseline risk factors. J Bone Miner Res 21:536–542
Rubin CT, Lanyon LE (1987) Kappa Delta Award paper. Osteoregulatory nature of mechanical stimuli: function as a determinant for adaptive remodeling in bone. J Orthop Res 5:300–310
Rudnick J, Puttmann B, Tesch PA, Alkner B, Schoser BG, Salanova M, Kirsch K, Gunga HC, Schiffl G, Luck G, Blottner D (2004) Differential expression of nitric oxide synthases (NOS 1–3) in human skeletal muscle following exercise countermeasure during 12 weeks of bed rest. FASEB J 18:1228–1230
Rudnick J, Puttmann B, Tesch PA, Alkner B, Schoser BG, Salanova M, Kirsch K, Gunga HC, Schiffl G, Luck G, Blottner D (2005) Differential expression of nitric oxide synthases (NOS 1–3) in human skeletal muscle following exercise countermeasure during 12 weeks of bed rest. Am J Physiol Endocrinol Metab 288:479–485
Ruegg DG, Kakebeeke TH, Gabriel JP, Bennefeld M (2002) Conduction velocity of nerve and muscle fiber action potentials after a space mission or a bed rest. Eur J Appl Physiol 88:193–202
Ruegg DG, Kakebeeke TH, Gabriel JP, Bennefeld M (2003) Conduction velocity of nerve and muscle fiber action potentials after a space mission or a bed rest. Clin Neurophysiol 114:86–93
Ruml LA, Dubois SK, Roberts ML, Pak CY (1995) Prevention of hypercalciuria and stone-forming propensity during prolonged bedrest by alendronate. J Bone Miner Res 10:655–662
Saivin S, Pavy-Le Traon A, Cornac A, Guell A, Houin G (1995) Impact of a four-day head-down tilt (-6 degrees) on lidocaine pharmacokinetics used as probe to evaluate hepatic blood flow. J Clin Pharmacol 35:697–704
Sandler H, Vernikos J (eds) (1986) Inactivity: physiological effects. Academic Press, New York, p 205
Sandler H, Goldwater DJ, Popp RL, Spaccavento L, Harrison DC (1985) Beta blockade in the compensation for bed-rest cardiovascular deconditioning: physiologic and pharmacologic observations. Am J Cardiol 55:114–119
Sangha DS, Vaziri ND, Ding Y, Purdy RE (2000) Vascular hyporesponsiveness in simulated microgravity: role of nitric oxide-dependent mechanisms. J Appl Physiol 88:507–517
Sasaki T, Iwasaki KI et al (1999) Effects of daily 2-Gz load on human cardiovascular function during weightlessness simulation using 4-day head-down bed rest. Uchu Koku Kankyo Igaku 36:113–123
Scheld K, Zittermann A, Heer M, Herzog B, Mika C, Drummer C, Stehle P (2001) Nitrogen metabolism and bone metabolism markers in healthy adults during 16 weeks of bed rest. Clin Chem 47:1688–1695
Scheltinga MR, Jacobs DO, Kimbrough TD, Wilmore DW (1991) Alterations in body fluid content can be detected by bioelectrical impedance analysis. J Surg Res 50:461–468
Schiessl H, Frost HM, Jee WSS (1998) Estrogen and bone-muscle strength and mass relationships. Bone 22:1–6
Schmedtje JF Jr, Liu WL, Taylor AA (1996) Cardiovascular deconditioning through head-down tilt bed rest increases blood pressure variability and plasma renin activity. Aviat Space Environ Med 67:539–546
Schmitt DA, Schaffar L, Taylor GR, Loftin KC, Schneider VS, Koebel A, Abbal M, Sonnenfeld G, Lewis DE, Reuben JR, Ferebee R (1996) Use of bed rest and head-down tilt to simulate spaceflight-induce immune system changes. J Interferon Cytokine Res 16:151–157
Schmitt DA, Schwarzenberg M, Tkaczuk J, Hebrard S, Brandenberger G, Mauco G, Cogoli-Greuter M, Abbal M (2000) Head-down tilt bed rest and immune responses. Pflugers Arch 441:79–84
Schneider SM, Watenpaugh DE, Lee SM, Ertl AC, Williams WJ, Ballard RE, Hargens AR (2002) Lower-body negative-pressure exercise and bed-rest-mediated orthostatic intolerance. Med Sci Sports Exerc 34:1446–1453
Scianowski J, Kedziora J, Zolynski K (1995) Red blood cell metabolism in men during long term bed rest. Int J Occup Med Environ Health 8:315–319
Seynnes OR, de Boer M, Narici MV (2007) Early skeletal muscle hypertrophy and architectural changes in response to high-intensity resistance training. J Appl Physiol 102:368–373
Shackelford LC, LeBlanc AD, Driscoll TB, Evans HJ, Rianon NJ, Smith SM, Spector E, Feeback DL, Lai D (2004) Resistance exercise as a countermeasure to disuse-induced bone loss. J Appl Physiol 97:119–129
Shangraw RE, Stuart C, Prince MJ, Peters EJ, Wolfe RR (1988) Insulin responsiveness of protein metabolism in vivo following bedrest in humans. Am J Physiol 255:548–558
Shen X, Dong Q, Chen J, Meng J, Jin Y, Wen Z, Zhang J (1997) Erythrocyte deformation in simulated weightless human and rabbits. J Gravit Physiol 4:61–65
Shibasaki M, Wilson TE, Cui J, Levine BD, Crandall CG (2003) Exercise throughout 6 degrees head-down tilt bed rest preserves thermoregulatory responses. J Appl Physiol 94:2330–2336
Shinohara M, Yoshitake Y, Kouzaki M, Fukuoka H, Fukunaga T (2003) Strength training counteracts motor performance losses during bed rest. J Appl Physiol 95:1485–1492
Shiraishi M, Kamo T, Nemoto S, Narita M, Kamegai M, Baevsky RM, Funtova II (2003) Blood pressure variability during 120-day head-down bed rest in humans. Biomed Pharmacother 57:35–38
Shoemaker JK, Hughson RL, Sinoway LI (2002) Gender affects sympathetic neurovascular control during postural stress. J Gravit Physiol 9:83–84
Shulzhenko EB, Vil-Viliams IF (1992) Short radius centrifuge as a method in long-term space flights. Physiologist 35:122–125
Sides MB, Vernikos J, Convertino VA, Stepanek J, Tripp LD, Draeger J, Hargens AR, Kourtidou-Papadeli C, Pavy-LeTraon A, Russomano T, Wong JY, Buccello RR, Lee PH, Nangalia V, Saary MJ (2005) The Bellagio report: cardiovascular risks of spaceflight: implications for the future of space travel. Aviat Space Environ Med 76:877–895
Sievanen H, Kannus P, Heinonen A, Oja P, Vuori I (1994a) Bone mineral density and muscle strength of lower extremities after long-term strength training, subsequent knee ligament injury and rehabilitation: a unique 2-year follow-up of a 26-year-old female student. Bone 15:85–90
Sievanen H, Kannus P, Oja P, Vuori I (1994b) Dual energy X-ray absorptiometry is also an accurate and precise method to measure the dimensions of human long bones. Calcif Tissue Int 54:101–105
Sievanen H, Koskue V, Rauhio A, Kannus P, Heinonen A, Vuori I (1998) Peripheral quantitative computed tomography in human long bones: evaluation of in vitro and in vivo precision. J Bone Miner Res 13:871–882
Sigaudo D, Fortrat JO, Maillet A, Allevard AM, Pavy-Le Traon A, Hughson RL, Guell A, Gharib C, Gauquelin G (1996) Comparison of a 4-day confinement and head-down tilt on endocrine response and cardiovascular variability in humans. Eur J Appl Physiol Occup Physiol 73:28–37
Sigaudo D, Fortrat JO, Allevard AM, Maillet A, Cottet-Emard JM, Vouillarmet A, Hughson RL, Gauquelin-Koch G, Gharib C (1998) Changes in the sympathetic nervous system induced by 42 days of head-down bed rest. Am J Physiol 274:1875–1884
Smith SM, Nillen JL, LeBlanc A, Lipton A, Demers LM, Lane HW, Leach CS (1998) Collagen cross-link excretion during space flight and bed rest. J Clin Endocrinol Metab 83:3584–3591
Smith SM, Wastney ME, Morukov BV, Larina IM, Nyquist LE, Abrams SA, Taran EN, Shih CY, Nillen JL, Davis-Street JE, Rice BL, Lane HW (1999) Calcium metabolism before, during, and after a 3-mo spaceflight: kinetic and biochemical changes. Am J Physiol 277:R1–R10
Smith SM, Davis-Street JE, Rice BL, Nillen JL, Gillman PL, Block G (2001) Nutritional status assessment in semiclosed environments: ground-based and space flight studies in humans. J Nutr 131:2053–2061
Smith SM, Davis-Street JE, Fesperman JV, Calkins DS, Bawa M, Macias BR, Meyer RS, Hargens AR (2003) Evaluation of treadmill exercise in a lower body negative pressure chamber as a countermeasure for weightlessness-induced bone loss: a bed rest study with identical twins. J Bone Miner Res 18:2223–2230
Smith SM, Dillon EL, DeKerlegand DE, Davis-Street JE (2004) Variability of collagen crosslinks: impact of sample collection period. Calcif Tissue Int 74:336–341
Smith SM, Zwart SR, Block G, Rice BL, Davis-Street JE (2005) The nutritional status of astronauts is altered after long-term space flight aboard the International Space Station. J Nutr 135:437–443
Smorawinski J, Kubala P, Kaciuba-Uociako H, Nazar K, Titow-Stupnicka E, Greenleaf JE (1996) Effects of three day bed-rest on circulatory, metabolic and hormonal responses to oral glucose load in endurance trained athletes and untrained subjects. J Gravit Physiol 3:44–45
Smorawinski J, Kaciuba-Uscilko H, Nazar K, Kubala P, Kaminska E, Ziemba AW, Adrian J, Greenleaf JE (2000) Effects of three-day bed rest on metabolic, hormonal and circulatory responses to an oral glucose load in endurance or strength trained athletes and untrained subjects. J Physiol Pharmacol 51:279–289
Spaak J, Sundblad P, Linnarsson D (2001) Impaired pressor response after spaceflight and bed rest: evidence for cardiovascular dysfunction. Eur J Appl Physiol 85:49–55
Stefanis N, Mackintosh C, Abraha HD, Treasure J, Moniz C (1998) Dissociation of bone turnover in anorexia nervosa. Ann Clin Biochem 35:709–716
Stein TP, Schluter MD, Leskiw MJ, Boden G (1999) Attenuation of the protein wasting associated with bed rest by branched-chain amino acids. Nutrition 15:656–660
Stein TP, Donaldson MR, Leskiw MJ, Schluter MD, Baggett DW, Boden G (2003) Branched-chain amino acid supplementation during bed rest: effect on recovery. J Appl Physiol 94:1345–1352
Strollo F, Riondino G, Harris B, Strollo G, Casarosa E, Mangrossa N, Ferretti C, Luisi M (1998) The effect of microgravity on testicular androgen secretion. Aviat Space Environ Med 69:133–136
Stuart CA, Shangraw RE, Prince MJ, Peters EJ, Wolfe RR (1988) Bed-rest-induced insulin resistance occurs primarily in muscle. Metabolism 37:802–806
Stuart CA, Shangraw RE, Peters EJ, Wolfe RR (1990) Effect of dietary protein on bed-rest-related changes in whole-body-protein synthesis. Am J Clin Nutr 52:509–514
Sun XQ, Yao YJ, Yang CB, Jiang SZ, Jiang CI, Liong WB (2005) Effect of lower-body negative pressure on cerebral blood flow velocity during 21 days head-down tilt bed rest. Med Sci Monit 11:1–5
Suzuki Y, Akima H, Igawa S, Fukunaga T, Kawakub K, Goto S, Makita Y, Gunji A (1996) Decrease of bone mineral density and muscle and/or strength in the leg during 20 days horizontal bed rest. J Gravit Physiol 3:42–43
Tabata I, Suzuki Y, Fukunaga T, Yokozeki T, Akima H, Funato K (1999) Resistance training affects GLUT-4 content in skeletal muscle of humans after 19 days of head-down bed rest. J Appl Physiol 86:909–914
Takenaka K, Suzuki Y, Kawakubo K, Haruna Y, Kuriyama K, Iwamoto S, Igarashi T, Watanabe F, Omata M, Bonde-Petersen F, Sekiguchi C, Murai T, Miyamoto A, Sudoh M, Akimura A, Gunji A, Miyamotoi A, Watanbe F (1997) Beta-blockade does not improve orthostatic intolerance induced by 20 days bed rest. J Gravit Physiol 4:69–71
Talbot HL, Fisher KD (1986) Influence of space flight on red blood cells. Federation Proc 45:2285–2290
Talbott SM, Shapses SA (1998) Fasting and energy intake influence bone turnover in lightweight male rowers. Int J Sport Nutr 8:377–387
Tessari P, Nosadini R, Trevisan R, De Kreutzenberg SV, Inchiostro S, Duner E, Biolo G, Marescotti MC, Tiengo A, Crepaldi G (1986) Defective suppression by insulin of leucine-carbon appearance and oxidation in type 1, insulin-dependent diabetes mellitus. Evidence for insulin resistance involving glucose and amino acid metabolism. J Clin Invest 77:1797–1804
Thompson JL (1998) Energy balance in young athletes. Int J Sport Nutr 8:160–174
Thornton W, Moore TP, Pool SL (1987) Fluid shifts in weightlessness. Aviat Space Environ Med 58:86–90
Trappe SW, Trappe TA, Lee GA, Widrick JJ, Costill DL, Fitts RH (2001) Comparison of a space shuttle flight (STS-78) and bed rest on human muscle function. J Appl Physiol 91:57–64
Trappe S, Trappe T, Gallagher P, Harber M, Alkner B, Tesch P (2004) Human single muscle fibre function with 84 day bed-rest and resistance exercise. J Physiol 557:501–513
Uebelhart D, Bernard J, Hartmann DJ, Moro L, Roth M, Uebelhart B, Rehailia M, Mauco G, Schmitt DA, Alexandre C, Vico L (2000) Modifications of bone and connective tissue after orthostatic bedrest. Osteoporos Int 11:59–67
Van der Wiel HE, Lips P, Nauta J, Netelenbos JC, Hazenberg GJ (1991) Biochemical parameters of bone turnover during ten days of bed rest and subsequent mobilization. Bone Miner 13:123–129
Van’t Hof RJ, Ralston SH (2001) Nitric oxide and bone. Immunology 103:255–261
Vaziri ND, Ding Y, Sangha DS, Purdy RE (2000) Upregulation of NOS by simulated microgravity, potential cause of orthostatic intolerance. J Appl Physiol 89:338–344
Vermeer C, Jie KS, Knapen MH (1995) Role of vitamin K in bone metabolism. Annu Rev Nutr 15:1–22
Vermeer C, Wolf J, Craciun AM, Knapen MH (1998) Bone markers during a 6-month space flight: Effects of vitamin K supplementation. J Gravit Physiol 5:66–69
Vernikos J (1997) Artificial gravity intermittent centrifugation as a space flight countermeasure. J Gravit Physiol 4:13–16
Vernikos J, Convertino VA (1994) Advantages and disadvantages of fludrocortisone or saline load in preventing post-spaceflight orthostatic hypotension. Acta Astronaut 33:259–266
Vernikos J, Dallman MF, Van Loon G, Keil LC (1991) Drug effects on orthostatic intolerance induced by bedrest. J Clin Pharmacol 31:974–984
Vernikos J, Dallman MF, Keil LC, O’Hara D, Convertino VA (1993) Gender differences in endocrine responses to posture and 7 days of -6 degrees head-down bed rest. Am J Physiol 265:153–161
Vernikos J, Ludwig DA, Ertl AC, Wade CE, Keil L, O’Hara D (1996) Effect of standing or walking on physiological changes induced by head down bed rest: implications for spaceflight. Aviat Space Environ Med 67:1069–1079
Vico L, Chappard D, Alexandre C, Palle S, Minaire P, Riffat G, Morukov B, Rakhmanov S (1987) Effects of a 120 day period of bed-rest on bone mass and bone cell activities in man: attempts at countermeasure. Bone Miner 2:383–394
Vico L, Bourrin S, Genty C, Palle S, Alexandre C (1993) Histomorphometric analyses of cancellous bone from COSMOS 2044 rats. J Appl Physiol 75:2203–2208
Vico L, Lafage-Proust MH, Alexandre C (1998) Effects of gravitational changes on the bone system in vitro and in vivo. Bone 22:95–100
Vico L, Collet P, Guignandon A, Lafage-Proust MH, Thomas T, Rehaillia M, Alexandre C (2000) Effects of long-term microgravity exposure on cancellous and cortical weight-bearing bones of cosmonauts. Lancet 355:1607–1611
Vijayan K, Thompson JL, Norenberg KM, Fitts RH, Riley DA (2001) Fiber-type susceptibility to eccentric contraction-induced damage of hindlimb-unloaded rat AL muscles. J Appl Physiol 90:770–776
Vil-Viliams IF (1994) Principle approaches to selection of the short-arm centrifuge regimens for extended space flight. Acta Astronaut 33:221–229
Vil-Viliams IF, Kotovskaya AR (1994) Changes of pulmonary function in humans during exposure to +Gx acceleration after simulated and real microgravity. J Gravit Physiol 1:129–132
Vil-Viliams IF, Shulzhenko EB (1980) Functional state of the cardiovascular system during combined exposure to 28-day immersion, rotation in a short-radius centrifuge, and physical loading on a bicycle ergometer. Kosm Biol Aviakosm Med 14:42–45
Vil-Viliams IF, Kotovskaya AR, Nikolashin GF, Lukjanuk VJ (2001) Modern view on the short arm centrifuge as a potential generator of artificial gravity in piloted missions. J Gravit Physiol 8:145–146
Vogel JM, Whittle MW (1976) Bone mineral changes: the second manned Skylab mission. Aviation Space Environ Med 47:396–400
Vukovich MD, Arciero PJ, Kohrt WM, Racette SB, Hansen PA, Holloszy JO (1996) Changes in insulin action and GLUT-4 with 6 days of inactivity in endurance runners. J Appl Physiol 80:240–244
Wang D, Xiang Q, Shen X, Yan H, Dong Q (1998a) Changes in cerebral circulation function during head down bed rest for 7 days. Space Med Med Eng 11:273–276
Wang D, Xiang Q, Shen X, Meng J, Dong Q (1998b) Effect of 7 d head down bed rest on cardiopulmonary circulation in human. Space Med Med Eng 1:177–180
Wang D, Xiang Q, Shen X, Meng J, Dong Q (1999) Effect of 7 d head down bed rest on cardiopulmonary circulation during orthostasis. Space Med Med Eng 12:125–129
Watenpaugh DE, Ballard RE, Schneider SM, Lee SM, Ertl AC, William JM, Boda WL, Hutchinson KJ, Hargens AR (2000) Supine lower body negative pressure exercise during bed rest maintains upright exercise capacity. J Appl Physiol 89:218–227
Watanabe Y, Ohshima H, Mizuno K, Sekiguchi C, Fukunaga M, Kohri K, Rittweger J, Felsenberg D, Matsumoto T, Nakamura T (2004) Intravenous pamidronate prevents femoral bone loss and renal stone formation during 90-day bed rest. J Bone Miner Res 19:1771–1778
Waters WW, Ziegler MG, Meck JV (2002) Postspaceflight orthostatic hypotension occurs mostly in women and is predicted by low vascular resistance. J Appl Physiol 92:586–594
Waters WW, Platts SH, Mitchell BM, Whitson PA, Meck JV (2005) Plasma volume restoration with salt tablets and water after bed rest prevents orthostatic hypotension and changes in supine hemodynamic and endocrine variables. Am J Physiol Heart Circ Physiol 288:839–847
Wegmann HM, Baisch F, Schaefer G (1984) Effect of 7 days antiorthostatic bedrest (6° HDT) on insulin responses to oral glucose load. Aviat Space Environ Med 55:443
Wei SQ, Su SN, Lu LL, Li YZ, Zhong CF, Ren HR (2003) Effects of 21 d -6 degrees head down bed-rest on pulmonary gas distribution and little airway function. Space Med Med Eng 16:93–95
Weinstein RS, Parfitt AM, Marcus R, Greenwald M, Crans G, Muchmore DB (2003) Effects of raloxifene, hormone replacement therapy, and placebo on bone turnover in postmenopausal women. Osteoporos Int 14:814–822
White WJ et al (1965) Biomedical potential of a centrifuge in an orbiting laboratory SSS-TDR-64–209, Suppl (Abstract)
White PD, Nyberg JW, Finney LM, White WJ (1966) Influence of periodic centrifugation on cardiovascular function of man during bed rest; Report n DAC–59286 (Abstract)
Widrick JJ, Knuth ST, Norenberg KM, Romatowski JG, Bain JL, Riley DA, Karhanek M, Trappe SW, Trappe TA, Costill DL, Fitts RH (1999) Effect of a 17 day spaceflight on contractile properties of human soleus muscle fibres. J Physiol 516:915–930
Widrick JJ, Romatowski JG, Norenberg KM, Knuth ST, Bain JL, Riley DA, Trappe SW, Trappe TA, Costill DL, Fitts RH (2001) Functional properties of slow and fast gastrocnemius muscle fibers after a 17-day spaceflight. J Appl Physiol 90:2203–2211
Wilhelm G, Felsenberg D, Bogusch G, Willnecker J, Thaten J, Gummert P (1999) Biomechanical examinations for validation of the bone strength strain index SSi, calculated by peripheral quantitative computer tomography. In: Lyritis G (ed) Musculoskeletal interactions. Hylonome Editions, Athens, pp 105–108
Wilkerson MK, Muller-Delp J, Colleran PN, Delp MD (1999) Effects of hindlimb unloading on rat cerebral, plenic and mesentreric resistance artery morphology. J Appl Physiol 87:2115–2121
Wilkerson MK, Lesniewski LA, Golding EM, Bryan RM Jr, Amin A, Wilson E, Delp MD (2005) Simulated microgravity enhances cerebral artery vasoconstruction and vascular resistance through endothelial nitric oxide mechanism. Am J Physiol Heart Circ Physiol 288:1652–1661
Williams WJ, Schneider SM, Gretebeck RJ, Lane HW, Stuart CA, Whitson PA (2003) Effect of dietary sodium on fluid/electrolyte regulation during bed rest. Aviat Space Environ Med 74:37–46
Wimalawansa SJ (2000) Nitroglycerin therapy is as efficacious as standard estrogen replacement therapy (Premarin) in prevention of oophorectomy-induced bone loss: a human pilot clinical study. J Bone Miner Res 15:2240–2244
Wimalawansa SM, Chapa MT, Wei JN, Westlund KN, Quast MJ, Wimalawansa SJ (1999) Reversal of weightlessness-induced musculoskeletal losses with androgens: quantification by MRI. J Appl Physiol 86:1841–1846
Wolff J (1899) Die Lehre von der functionellen Knochengestalt. Archiv Pathol Anat Physiol 155:256–315
Xiao X, Mukkamala R, Sheynberg N, Williams GH, Cohen RJ (2002) Effects of prolonged bed rest on the total peripheral resistance baroreflex. Comput Cardiol 29:53–56
Yajima K, Iwasaki K et al (2000) Can daily centrifugation prevent the haematocrit increase elicited by 6-degree head-down tilt? P flugers Archiv 441:95–97
Yajima K, Miyamoto A, Ito M, Maru R, Maeda T, Sanada E, Nakazato T, Saiki C, Yamaguchi Y, Igarashi M, Matsumoto S (1994) Human cardiovascular and vestibular responses in long minutes and low +Gz loading by a short arm centrifuge. Acta Astronaut 33:239–252
Yamamoto Y, Hughson RL (1991) Coarse-graining spectral analysis: new method for studying heart rate variability. J Appl Physiol 71:1143–1450
Yamamoto T, Sekiya N, Miyashita S, Asada H, Yano Y, Morishima K, Okamoto Y, Goto S, Suzuki Y, Gunji A (1997) Gender differences in effects of 20 days horizontal bed rest on muscle strength in young subjects. J Gravit Physiol 4:31–36
Yamanaka K, Yamamoto S, Nakazawa K, Yano H, Suzuki Y, Fukunaga T (1999) The effects of long-term bed rest on H-reflex and motor evoked potential in the human soleus muscle during standing. J Gravit Physiol 6:157–158
Yamashita-Goto K, Okuyama R, Honda M, Kawasaki K, Fujita K, Yamada T, Nonaka I, Ohira Y, Yoshioka T (2001) Maximal and submaximal forces of slow fibers in human soleus after bed rest. J Appl Physiol 91:417–424
Yanagibori R, Suzuki Y, Kawakubo K, Makita Y, Gunji A (1994) Carbohydrate and lipid metabolism after 20 days of bed rest. Acta Physiol Scand 616(Suppl):51–57
Yanagibori R, Suzuki Y, Kawakubo K, Kondo K, Iwamoto T, Itakura H, Makita Y, Sekiguchi C, Gunji A, Kondou K (1997) The effects of 20 days bed rest on serum lipids and lipoprotein concentrations in healthy young subjects. J Gravit Physiol 4:82–90
Yates BJ, Kerman IA (1998) Post-spaceflight orthostatic intolerance: possible relationship to microgravity-induced plasticity in the vestibular system. Brain Res Rev 28:73–82
Zachwieja JJ, Smith SR, Lovejoy JC, Rood JC, Windhauser MM, Bray GA (1999) Testosterone administration preserves protein balance but not muscle strength during 28 days of bed rest. J Clin Endocrinol Metab 84:207–212
Zange J, Muller K, Schuber M, Wackerhage H, Hoffmann U, Gunther RW, Adam G, Neuerburg JM, Sinitsyn VE, Bacharev AO, Belichenko OI (1997) Changes in calf muscle performance, energy metabolism, and muscle volume caused by long-term stay on space station MIR. Int J Sports Med 18:308–309
Zerwekh JE, Ruml LA, Gottschalk F, Pak CY (1998) The effects of twelve weeks of bed rest on bone histology, biochemical markers of bone turnover, and calcium homeostasis in eleven normal subjects. J Bone Miner Res 13:1594–1601
Zezerov AE, Ivanova SM, Morukov BV, Ushakov AS (1989) Lipid peroxidation in the human blood during a 120-day period of anti-orthostatic hypokinesia. Biol Aviakosm Med 23:28–33
Zezerov AE, Ivanova SM, Morukov BV, Ushakov AS (1996) Lipid peroxidation in the human blood during a 120-day period of anti-orthostatic hypokinesia. J Gravit Physiol 3:1–4
Zhang LF (2001) Vascular adaptation to microgravity: what have we learned? J Appl Physiol 91:2415–2430
Zhang R, Zuckerman JH, Pawelczyk JA, Levine BD (1997) Effects of head-down-tilt bed rest on cerebral hemodynamics during orthostatic stress. J Appl Physiol 83:2139–2145
Zittermann A (2003) Vitamin D in preventive medicine: are we ignoring the evidence? Br J Nutr 89:552–572
Zittermann A, Heer M, Caillot-Augusso A, Rettberg P, Scheld K, Drummer C, Alexandre C, Horneck G, Vorobiev D, Stehle P (2000) Microgravity inhibits intestinal calcium absorption as shown by a stable strontium test. Eur J Clin Invest 30:1036–1043
Zittermann A, Dembinski J, Stehle P (2004) Low vitamin D status is associated with low cord blood levels of the immunosuppressive cytokine interleukin-10. Pediatr Allergy Immunol 15:242–246
Zittermann A, Schleithoff SS, Koerfer R (2005) Putting cardiovascular disease and vitamin D insufficiency into perspective. Br J Nutr 94:483–492
Zwart SR, Hargens AR, Smith SM (2004) The ratio of animal protein intake to potassium intake is a predictor of bone resorption in space flight analogues and in ambulatory subjects. Am J Clin Nutr 80:1058–1065
Acknowledgements
This review is based on many excellent research studies carried out over the last 20 years. Scientists who performed them and the supporting Space Agencies and organisations are greatly acknowledged. We also thank all the volunteers who participated to these experiments. We express our gratitude to Mrs V. Rayjal for her help in the preparation of this manuscript.
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Pavy-Le Traon, A., Heer, M., Narici, M.V. et al. 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). https://doi.org/10.1007/s00421-007-0474-z
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DOI: https://doi.org/10.1007/s00421-007-0474-z