Abstract
In 1991, Hans Berg and colleagues published the first research investigation using unilateral lower limb suspension (ULLS) as a human model to study the influence of unloading on skeletal muscle. ULLS requires a participant to perform all activities with axillary crutches while wearing one thick-soled shoe. The elevated shoe eliminates ground contact with the adjacent foot, thereby unloading the lower limb. Today, ULLS is a well-known ground-based analog for microgravity. The present review will synthesize the physiological findings from investigations using ULLS to study the deleterious effects of unloading. Compromised human performance and the neuromuscular, musculoskeletal and circulatory mechanisms leading to altered function will be a major emphasis of the work. Results from prolonged bed rest will also be included in order for general comparisons to be made between analogs. Finally, the efficacy of exercise to mitigate the negative consequences of unloading is presented.
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Aagaard P, Simonsen EB, Andersen JL, Magnusson P, Dyhre-Poulsen P (2002) Neural adaptation to resistance training: changes in evoked V-wave and H-reflex responses. J Appl Physiol 92:2309–2318
Abe T, Kearns CF, Sato Y (2006) Muscle size and strength are increased following walk training with restricted venous blood flow from the leg muscle, Kaatsu-walk training. J Appl Physiol 100:1460–1466
Adams GR (2002) Human unilateral lower limb suspension as a model for spaceflight effects on skeletal muscle. J Appl Physiol 93:1563–1565 author reply 1565–1566
Adams GR, Duvoisin MR, Dudley GA (1992) Magnetic resonance imaging and electromyography as indexes of muscle function. J Appl Physiol 73:1578–1583
Adams GR, Hather BM, Dudley GA (1994) Effect of short-term unweighting on human skeletal muscle strength and size. Aviat Space Environ Med 65:1116–1121
Adams GR, Caiozzo VJ, Baldwin KM (2003) Skeletal muscle unweighting: spaceflight and ground-based models. J Appl Physiol 95:2185–2201
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, Hotta N, Sato K, Ishida K, Koike T, Katayama K (2009) Cycle ergometer exercise to counteract muscle atrophy during unilateral lower limb suspension. Aviat Space Environ Med 80:652–656
Allen DG, Lamb GD, Westerblad H (2008) Skeletal muscle fatigue: cellular mechanisms. Physiol Rev 88:287–332
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
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, Dudley GA, Hather B, Tesch PA (1993) Work capacity and metabolic and morphologic characteristics of the human quadriceps muscle in response to unloading. Clin Physiol 13:337–347
Berg HE, Larsson L, Tesch PA (1997) Lower limb skeletal muscle function after 6 wk of bed rest. J Appl Physiol 82:182–188
Bleeker MW, Hopman MT, Rongen GA, Smits P (2004) Unilateral lower limb suspension can cause deep venous thrombosis. Am J Physiol Regul Integr Comp Physiol 286:R1176–R1177
Bleeker MW, De Groot PC, Poelkens F, Rongen GA, Smits P, Hopman MT (2005a) Vascular adaptation to 4 wk of deconditioning by unilateral lower limb suspension. Am J Physiol Heart Circ Physiol 288:H1747–H1755
Bleeker MW, Kooijman M, Rongen GA, Hopman MT, Smits P (2005b) Preserved contribution of nitric oxide to baseline vascular tone in deconditioned human skeletal muscle. J Physiol 565:685–694
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
Booth FW (1977) Time course of muscular atrophy during immobilization of hindlimbs in rats. J Appl Physiol 43:656–661
Booth FW, Gollnick PD (1983) Effects of disuse on the structure and function of skeletal muscle. Med Sci Sports Exerc 15:415–420
Byrne B (2001) Deep vein thrombosis prophylaxis: the effectiveness and implications of using below-knee or thigh-length graduated compression stockings. Heart Lung 30:277–284
Carrithers JA, Tesch PA, Trieschmann J, Ekberg A, Trappe TA (2002) Skeletal muscle protein composition following 5 weeks of ULLS and resistance exercise countermeasures. J Gravit Physiol 9:P155–P156
Carson JA, Wei L (2000) Integrin signaling’s potential for mediating gene expression in hypertrophying skeletal muscle. J Appl Physiol 88:337–343
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
Caruso JF, Hamill JL, Yamauchi M, Cook TD, Mercado DR, Wickel EE (2008) Albuterol and exercise effects on ankle extensor strength during 40 days of unloading. Aviat Space Environ Med 79:577–584
Clark BC, Fernhall B, Ploutz-Snyder LL (2006a) Adaptations in human neuromuscular function following prolonged unweighting: I. Skeletal muscle contractile properties and applied ischemia efficacy. J Appl Physiol 101:256–263
Clark BC, Manini TM, Bolanowski SJ, Ploutz-Snyder LL (2006b) Adaptations in human neuromuscular function following prolonged unweighting: II. Neurological properties and motor imagery efficacy. J Appl Physiol 101:264–272
Clark BC, Cook SB, Ploutz-Snyder LL (2007a) Reliability of techniques to assess human neuromuscular function in vivo. J Electromyogr Kinesiol 17:90–101
Clark BC, Pierce JR, Manini TM, Ploutz-Snyder LL (2007b) Effect of prolonged unweighting of human skeletal muscle on neuromotor force control. Eur J Appl Physiol 100:53–62
Convertino VA, Doerr DF, Mathes KL, Stein SL, Buchanan P (1989) Changes in volume, muscle compartment, and compliance of the lower extremities in man following 30 days of exposure to simulated microgravity. Aviat Space Environ Med 60:653–658
Cook SB, Clark BC, Ploutz-Snyder LL (2006) Accelerometry as a measure of subject compliance in unilateral lower limb suspension. Aviat Space Environ Med 77:953–956
Cook SB, Brown KA, Deruisseau KC, Kanaley JA, Ploutz-Snyder LL (2010) Skeletal muscle adaptations following blood flow restricted training during 30 days of muscular unloading. J Appl Physiol 2:341–349
Danielsen CC, Andreassen TT (1988) Mechanical properties of rat tail tendon in relation to proximal-distal sampling position and age. J Biomech 21:207–212
de Boer MD, Maganaris CN, Seynnes OR, Rennie MJ, Narici MV (2007a) Time course of muscular, neural and tendinous adaptations to 23 day unilateral lower-limb suspension in young men. J Physiol 583:1079–1091
de Boer MD, Selby A, Atherton P, Smith K, Seynnes OR, Maganaris CN, Maffulli N, Movin T, Narici MV, Rennie MJ (2007b) The temporal responses of protein synthesis, gene expression and cell signalling in human quadriceps muscle and patellar tendon to disuse. J Physiol 585:241–251
de Boer MD, Seynnes OR, di Prampero PE, Pisot R, Mekjavic IB, Biolo G, Narici MV (2008) Effect of 5 weeks horizontal bed rest on human muscle thickness and architecture of weight bearing and non-weight bearing muscles. Eur J Appl Physiol 104:401–407
Duchateau J (1995) Bed rest induces neural and contractile adaptations in triceps surae. Med Sci Sports Exerc 27:1581–1589
Dudley GA, Duvoisin MR, Adams GR, Meyer RA, Belew AH, Buchanan P (1992a) Adaptations to unilateral lower limb suspension in humans. Aviat Space Environ Med 63:678–683
Dudley GA, Hather BM, Buchanan P (1992b) Skeletal muscle responses to unloading with special reference to man. J Fla Med Assoc 79:525–529
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 270:E627–E633
Gamrin L, Berg HE, Essen P, Tesch PA, Hultman E, Garlick PJ, McNurlan MA, Wernerman J (1998) The effect of unloading on protein synthesis in human skeletal muscle. Acta Physiol Scand 163:369–377
Gibson JN, Halliday D, Morrison WL, Stoward PJ, Hornsby GA, Watt PW, Murdoch G, Rennie MJ (1987) Decrease in human quadriceps muscle protein turnover consequent upon leg immobilization. Clin Sci 72:503–509
Goldspink DF, Morton AJ, Loughna P, Goldspink G (1986) The effect of hypokinesia and hypodynamia on protein turnover and the growth of four skeletal muscles of the rat. Pflugers Arch 407:333–340
Greenleaf JE (1997) Intensive exercise training during bed rest attenuates deconditioning. Med Sci Sports Exerc 29:207–215
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
Grichko VP, Heywood-Cooksey A, Kidd KR, Fitts RH (2000) Substrate profile in rat soleus muscle fibers after hindlimb unloading and fatigue. J Appl Physiol 88:473–478
Gustafsson T, Osterlund T, Flanagan JN, von Waldén F, Trappe TA, Linnehan RM, Tesch PA (2010) Effects of 3 days unloading on molecular regulators of muscle size in humans. J Appl Physiol 109(3):721–727. doi: 10.1152/japplphysiol.00110.2009
Haddad F, Baldwin KM, Tesch PA (2005) Pretranslational markers of contractile protein expression in human skeletal muscle: effect of limb unloading plus resistance exercise. J Appl Physiol 98:46–52
Hather BM, Adams GR, Tesch PA, Dudley GA (1992) Skeletal muscle responses to lower limb suspension in humans. J Appl Physiol 72:1493–1498
Haus JM, Carrithers JA, Carroll CC, Tesch PA, Trappe TA (2007) Contractile and connective tissue protein content of human skeletal muscle: effects of 35 and 90 days of simulated microgravity and exercise countermeasures. Am J Physiol Regul Integr Comp Physiol 293:R1722–R1727
Hepple RT (2000) Skeletal muscle: microcirculatory adaptation to metabolic demand. Med Sci Sports Exerc 32:117–123
Hickson RC (1980) Interference of strength development by simultaneously training for strength and endurance. Eur J Appl Physiol Occup Physiol 45:255–263
Hikida RS, Gollnick PD, Dudley GA, Convertino VA, Buchanan P (1989) Structural and metabolic characteristics of human skeletal muscle following 30 days of simulated microgravity. Aviat Space Environ Med 60:664–670
Hotta N, Sato K, Katayama K, Koga S, Masuda K, Miyachi M, Akima H, Ishida K (2006) Oxygen uptake kinetics following 20 days of unilateral lower limb suspension. J Physiol Sci 56:347–353
Hotta N, Ishida K, Sato K, Koike T, Katayama K, Akima H (2010) The effect of intense interval cycle-training on unloading-induced dysfunction and atrophy in the human calf muscle. J Physiol Anthropol 30:29–35
Ito T, Tagawa Y, Shiba N, Tanaka S, Umezu Y, Yamamoto T, Basford JR (2004) Development of practical and effective hybrid exercise for use in weightless environment. Conf Proc IEEE Eng Med Biol Soc 6:4252–4255
Jenkins M, Malloy P, Salloway S, Cohen R, Rogg J, Tung G, Kohn R, Westlake R, Johnson EG, Richardson E (1998) Memory processes in depressed geriatric patients with and without subcortical hyperintensities on MRI. J Neuroimaging 8:20–26
Jones DA (1996) High-and low-frequency fatigue revisited. Acta Physiol Scand 156:265–270
Jones D, Round J, De Haan A (2004) Skeletal muscle from molecules to movement: a textbook of muscle physiology for sport, exercise, physiotherapy and medicine. Churchill Livingstone, Edinburgh
Kamiya A, Iwase S, Michikami D, Fu Q, Mano T, Kitaichi K, Takagi K (2000) Increased vasomotor sympathetic nerve activity and decreased plasma nitric oxide release after head-down bed rest in humans: disappearance of correlation between vasoconstrictor and vasodilator. Neurosci Lett 281:21–24
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
Keenan KG, Farina D, Merletti R, Enoka RM (2006) Influence of motor unit properties on the size of the simulated evoked surface EMG potential. Exp Brain Res 169:37–49
Kim BJ, Date ES, Park BK, Choi BY, Lee SH (2005) Physiologic changes of compound muscle action potentials related to voluntary contraction and muscle length in carpal tunnel syndrome. J Electromyogr Kinesiol 15:275–281
Kinugasa R, Hodgson JA, Edgerton VR, Shin DD, Sinha S (2010) Reduction in tendon elasticity from unloading is unrelated to its hypertrophy. J Appl Physiol 109(3):870–877
Kubo K, Akima H, Kouzaki M, Ito M, Kawakami Y, Kanehisa H, Fukunaga T (2000) Changes in the elastic properties of tendon structures following 20 days bed-rest in humans. Eur J Appl Physiol 83:463–468
Kubo K, Akima H, Ushiyama J, Tabata I, Fukuoka H, Kanehisa H, Fukunaga T (2004) 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
Lee HD, Finni T, Hodgson JA, Lai AM, Edgerton VR, Sinha S (2006) Soleus aponeurosis strain distribution following chronic unloading in humans: an in vivo MR phase-contrast study. J Appl Physiol 100:2004–2011
Lidegaard O, Edstrom B, Kreiner S (2002) Oral contraceptives and venous thromboembolism: a five year national case-control study. Contraception 65:187–196
Louisy F, Schroiff P, Guell A (1997) Changes in leg vein filling and emptying characteristics and leg volumes during long-term head-down bed rest. J Appl Physiol 82:1726–1733
Manini TM, Clark BC (2009) Blood flow restricted exercise and skeletal muscle health. Exerc Sport Sci Rev 37:78–85
Manini TM, Clark BC, Nalls MA, Goodpaster BH, Ploutz-Snyder LL, Harris TB (2007) Reduced physical activity increases intermuscular adipose tissue in healthy young adults. Am J Clin Nutr 85:377–384
Musacchia XJ, Steffen JM, Fell RD (1988) Disuse atrophy of skeletal muscle: animal models. Exerc Sport Sci Rev 16:61–87
Narici MV, de Boer MD (2011) Disuse of the musculo-skeletal system in space and on earth. Eur J Appl Physiol 111(3):403–420
Nobrega AC, Williamson JW, Mitchell JH (1995) Left ventricular volumes and hemodynamic responses at onset of dynamic exercise with reduced venous return. J Appl Physiol 79:1405–1410
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
Pavy-Le Traon A, Heer M, Narici MV, Rittweger J, Vernikos J (2007) From space to Earth: advances in human physiology from 20 years of bed rest studies (1986–2006). Eur J Appl Physiol 101:143–194
Pierce JR, Clark BC, Ploutz-Snyder LL, Kanaley JA (2006) Growth hormone and muscle function responses to skeletal muscle ischemia. J Appl Physiol 101:1588–1595
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
Ploutz-Snyder LL, Tesch PA, Hather BM, Dudley GA (1996) Vulnerability to dysfunction and muscle injury after unloading. Arch Phys Med Rehabil 77:773–777
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
Proske U, Morgan DL (1987) Tendon stiffness: methods of measurement and significance for the control of movement. A review. J Biomech 20:75–82
Reeves ND, Narici MV, Maganaris CN (2003) Strength training alters the viscoelastic properties of tendons in elderly humans. Muscle Nerve 28:74–81
Rennie MJ, Phillips S, Smith K (2008) Reliability of results and interpretation of measures of 3-methylhistidine in muscle interstitium as marker of muscle proteolysis. J Appl Physiol 105:1380–1381 author reply 1382–1383
Rittweger J, Winwood K, Seynnes O, de Boer M, Wilks D, Lea R, Rennie M, Narici M (2006) Bone loss from the human distal tibia epiphysis during 24 days of unilateral lower limb suspension. J Physiol 577:331–337
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
Sakuma K, Watanabe K, Hotta N, Koike T, Ishida K, Katayama K, Akima H (2009) The adaptive responses in several mediators linked with hypertrophy and atrophy of skeletal muscle after lower limb unloading in humans. Acta Physiol 197:151–159
Sargeant AJ, Davies CT, Edwards RH, Maunder C, Young A (1977) Functional and structural changes after disuse of human muscle. Clin Sci Mol Med 52:337–342
Sato K, Katayama K, Hotta N, Ishida K, Akima H (2010) Aerobic exercise capacity and muscle volume after lower limb suspension with exercise countermeasure. Aviat Space Environ Med 81:1085–1091
Schieppati M (1987) The Hoffmann reflex: a means of assessing spinal reflex excitability and its descending control in man. Prog Neurobiol 28:345–376
Schulze K, Gallagher P, Trappe S (2002) Resistance training preserves skeletal muscle function during unloading in humans. Med Sci Sports Exerc 34:303–313
Seynnes OR, Maffiuletti NA, Maganaris CN, de Boer MD, Pensini M, di Prampero PE, Narici MV (2008a) Soleus T reflex modulation in response to spinal and tendinous adaptations to unilateral lower limb suspension in humans. Acta Physiol 194:239–251
Seynnes OR, Maganaris CN, de Boer MD, di Prampero PE, Narici MV (2008b) Early structural adaptations to unloading in the human calf muscles. Acta Physiol 193:265–274
Seynnes OR, Maffiuletti NA, Horstman AM, Narici MV (2010) Increased H-reflex excitability is not accompanied by changes in neural drive following 24 days of unilateral lower limb suspension. Muscle Nerve 42(5):749–755
Shin D, Finni T, Ahn S, Hodgson JA, Lee HD, Edgerton VR, Sinha S (2008) Effect of chronic unloading and rehabilitation on human Achilles tendon properties: a velocity-encoded phase-contrast MRI study. J Appl Physiol 105:1179–1186
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
Spiering BA, Kraemer WJ, Anderson JM, Armstrong LE, Nindl BC, Volek JS, Maresh CM (2008) Resistance exercise biology: manipulation of resistance exercise programme variables determines the responses of cellular and molecular signalling pathways. Sports Med 38:527–540
Sreter FA (1963) Distribution of water, sodium, and potassium in resting and stimulated mammalian muscle. Can J Biochem Physiol 41:1035–1045
Takarada Y, Nakamura Y, Aruga S, Onda T, Miyazaki S, Ishii N (2000) Rapid increase in plasma growth hormone after low-intensity resistance exercise with vascular occlusion. J Appl Physiol 88:61–65
Takarada Y, Sato Y, Ishii N (2002) Effects of resistance exercise combined with vascular occlusion on muscle function in athletes. Eur J Appl Physiol 86:308–314
Tesch PA, Ploutz LL, Dudley GA (1994) Effects of 5 weeks of lower limb suspension on muscle size and strength. J Gravit Physiol 1:P59–P60
Tesch PA, Trieschmann JT, Ekberg A (2004) Hypertrophy of chronically unloaded muscle subjected to resistance exercise. J Appl Physiol 96:1451–1458
Tesch PA, von Walden F, Gustafsson T, Linnehan RM, Trappe TA (2008) Skeletal muscle proteolysis in response to short-term unloading in humans. J Appl Physiol 105:902–906
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
Widrick JJ, Romatowski JG, Bain JL, Trappe SW, Trappe TA, Thompson JL, Costill DL, Riley DA, Fitts RH (1997) Effect of 17 days of bed rest on peak isometric force and unloaded shortening velocity of human soleus fibers. Am J Physiol 273:C1690–C1699
Widrick JJ, Trappe SW, Romatowski JG, Riley DA, Costill DL, Fitts RH (2002) Unilateral lower limb suspension does not mimic bed rest or spaceflight effects on human muscle fiber function. J Appl Physiol 93:354–360
Zhu X, Topouzis S, Liang LF, Stotish RL (2004) Myostatin signaling through Smad2, Smad3 and Smad4 is regulated by the inhibitory Smad7 by a negative feedback mechanism. Cytokine 26:262–272
Acknowledgments
We would like to thank Dr. Gregory Adams, University of California Irvine for reviewing the manuscript. We thank both the dedicated researchers and ULLS study participants for their commitment to scientific discovery. This work was partially supported by the National Aeronautics and Space Administration Graduate Student Research Program Training Grant (NNX08AW71H).
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Communicated by Nigel A. S. Taylor.
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Hackney, K.J., Ploutz-Snyder, L.L. Unilateral lower limb suspension: integrative physiological knowledge from the past 20 years (1991–2011). Eur J Appl Physiol 112, 9–22 (2012). https://doi.org/10.1007/s00421-011-1971-7
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DOI: https://doi.org/10.1007/s00421-011-1971-7