Biomarkers of peripheral muscle fatigue during exercise

BMC Musculoskeletal Disorders

Josef Finsterer¹ 

[1]Krankenanstalt Rudolfstiftung, Postfach 20, 1180, Vienna, Austria

关键词: Exercise fatigue;    Muscle exercise;    Monitoring;    Muscle fatigue;    Biological marker;    Biomarker;   

Others  :  1135731
DOI  :  10.1186/1471-2474-13-218

 received in 2012-05-23, accepted in 2012-10-10,  发布年份 2012

【 摘 要 】

Background

Biomarkers of peripheral muscle fatigue (BPMFs) are used to offer insights into mechanisms of exhaustion during exercise in order to detect abnormal fatigue or to detect defective metabolic pathways. This review aims at describing recent advances and future perspectives concerning the most important biomarkers of muscle fatigue during exercise.

Results

BPMFs are classified according to the mechanism of fatigue related to adenosine-triphosphate-metabolism, acidosis, or oxidative-metabolism. Muscle fatigue is also related to an immunological response. impaired calcium handling, disturbances in bioenergetic pathways, and genetic responses. The immunological and genetic response may make the muscle susceptible to fatigue but may not directly cause muscle fatigue. Production of BPMFs is predominantly dependent on the type of exercise. BPMFs need to change as a function of the process being monitored, be stable without appreciable diurnal variations, correlate well with exercise intensity, and be present in detectable amounts in easily accessible biological fluids. The most well-known BPMFs are serum lactate and interleukin-6. The most widely applied clinical application is screening for defective oxidative metabolism in mitochondrial disorders by means of the lactate stress test. The clinical relevance of most other BPMFs, however, is under debate, since they often depend on age, gender, physical fitness, the energy supply during exercise, the type of exercise needed to produce the BPMF, and whether healthy or diseased subjects are investigated.

Conclusions

Though the role of BPMFs during fatigue is poorly understood, measuring BPMFs under specific, standardised conditions appears to be helpful for assessing biological states or processes during exercise and fatigue.

【 授权许可】

   
2012 Finsterer; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Rondelli RR, Dal Corso S, Simões A, Malaguti C: Methods for the assessment of peripheral muscle fatigue and its energy and metabolic determinants in COPD. J Bras Pneumol 2009, 35:1125-1135.
• [2]Boyas S, Guével A: Neuromuscular fatigue in healthy muscle: underlying factors and adaptation mechanisms. Ann Phys Rehabil Med 2011, 54:88-108.
• [3]Spruit MA, Thomeer MJ, Gosselink R, Troosters T, Kasran A, Debrock AJ, Demedts MG, Decramer M: Skeletal muscle weakness in patients with sarcoidosis and its relationship with exercise intolerance and reduced health status. Thorax 2005, 60:32-38.
• [4]Gosker HR, Schols AM: Fatigued muscles in COPD but no finishing line in sight. Eur Respir J 2008, 31:693-694.
• [5]Rainoldi A, Gazzoni M, Merletti R, Minetto MA: Mechanical and EMG responses of the vastus lateralis and changes in biochemical variables to isokinetic exercise in endurance and power athletes. J Sports Sci 2008, 26:321-331.
• [6]Pette D: Adaptation of skeletal muscle to increased neuromuscular activity as induced by chronic low frequency stimulation. Scand J Rehabil Med Suppl 1994, 30:7-18.
• [7]McMullen CA, Hayess K, Andrade FH: Fatigue resistance of rat extraocular muscles does not depend on creatine kinase activity. BMC Physiol 2005, 17(5):12.
• [8]Brandt C, Pedersen BK: The role of exercise-induced myokines in muscle homeostasis and the defense against chronic diseases. J Biomed Biotechnol 2010. in press.
• [9]Pedersen BK: IL-6 signaling in exercise and disease. Biochem Soc Trans 2007, 35:1295-7.
• [10]Margonis K, Fatouros IG, Jamurtas AZ, Nikolaidis MG, Douroudos I, Chatzinikolaou A, Mitrakou A, Mastorakos G, Papassotiriou I, Taxildaris K, Kouretas D: Oxidative stress biomarkers responses to physical overtraining: implications for diagnosis. Free Radic Biol Med 2007, 43:901-10.
• [11]Simpson RJ, Florida-James GD, Cosgrove C, Whyte GP, Macrae S, Pircher H, Guy K: High-intensity exercise elicits the mobilization of senescent T lymphocytes into the peripheral blood compartment in human subjects. J Appl Physiol 2007, 103:396-401.
• [12]Stenholm S, Maggio M, Lauretani F, Bandinelli S, Ceda GP, Di Iorio A, Giallauria F, Guralnik JM, Ferrucci L: Anabolic and catabolic biomarkers as predictors of muscle strength decline: the InCHIANTI study. Rejuvenation Res 2010, 13:3-11.
• [13]Burke RE, Levine DN, Tsairis P, Zajac FE 3rd: Physiological types and histochemical profiles in motor units of the cat gastrocnemius. J Physiol 1973, 234:723-48.
• [14]Westerblad H, Bruton JD, Lännergren J: The effect of intracellular pH on contractile function of intact, single fibres of mouse muscle declines with increasing temperature. J Physiol 1997, 500:193-204.
• [15]Fitts RH: Muscle fatigue: the cellular aspects. Am J Sports Med 1996, 24(suppl):S9-13.
• [16]Jones DA, Turner DL, McIntyre DB, Newham DJ: Energy turnover in relation to slowing of contractile properties during fatiguing contractions of the human anterior tibialis muscle. J Physiol 2009, 587:4329-38.
• [17]Hancock CR, Brault JJ, Wiseman RW, Terjung RL, Meyer RA: 31P-NMR observation of free ADP during fatiguing, repetitive contractions of murine skeletal muscle lacking AK1. Am J Physiol Cell Physiol 2005, 288:C1298-304.
• [18]Korzeniewski B: AMP deamination delays muscle acidification during heavy exercise and hypoxia. J Biol Chem 2006, 281:3057-66.
• [19]Glaister M: Multiple-sprint work: methodological, physiological, and experimental issues. Int J Sports Physiol Perform 2008, 3:107-12.
• [20]Bellinger AM, Mongillo M, Marks AR: Stressed out: the skeletal muscle ryanodine receptor as a target of stress. J Clin Invest 2008, 118:445-53.
• [21]van Hall G: Lactate kinetics in human tissues at rest and during exercise. Acta Physiol (Oxf) 2010, 199:499-508.
• [22]Finsterer J, Milvay E: Lactate stress testing in 155 patients with mitochondriopathy. Can J Neurol Sci 2002, 29:49-53.
• [23]Siegel AJ, Januzzi J, Sluss P, Lee-Lewandrowski E, Wood M, Shirey T, Lewandrowski KB: Cardiac biomarkers, electrolytes, and other analytes in collapsed marathon runners: implications for the evaluation of runners following competition. Am J Clin Pathol 2008, 129:948-51.
• [24]Skurvydas A, Streckis V, Mickeviciene D, Kamandulis S, Stanislovaitis A, Mamkus G: Effect of age on metabolic fatigue and on indirect symptoms of skeletal muscle damage after stretch-shortening exercise. J Sports Med Phys Fitness 2006, 46:431-41.
• [25]Schuback K, Essén-Gustavsson B, Persson SG: Incremental treadmill exercise until onset of fatigue and its relationship to metabolic response and locomotion pattern. Equine Vet J Suppl 1999, 30:337-41.
• [26]Maltais F, Simard AA, Simard C, Jobin J, Desgagnés P, LeBlanc P: Oxidative capacity of the skeletal muscle and lactic acid kinetics during exercise in normal subjects and in patients with COPD. Am J Respir Crit Care Med 1996, 153:288-93.
• [27]Hancock CR, Janssen E, Terjung RL: Contraction-mediated phosphorylation of AMPK is lower in skeletal muscle of adenylate kinase-deficient mice. J Appl Physiol 2006, 100:406-13.
• [28]Myburgh KH: Protecting muscle ATP: positive roles for peripheral defense mechanisms-introduction. Med Sci Sports Exerc 2004, 36:16-9.
• [29]Hardie DG: AMP-activated protein kinase: a key system mediating metabolic responses to exercise. Med Sci Sports Exerc 2004, 36:28-34.
• [30]Galal NM, Fouad HM, Saied A, Dabnon M: Hyperammonemia in the pediatric emergency care setting. Pediatr Emerg Care 2010, 26:888-91.
• [31]Esbjörnsson M, Norman B, Suchdev S, Viru M, Lindhgren A, Jansson E: Greater growth hormone and insulin response in women than in men during repeated bouts of sprint exercise. Acta Physiol (Oxf) 2009, 197:107-15.
• [32]Calvert LD, Singh SJ, Greenhaff PL, Morgan MD, Steiner MC: The plasma ammonia response to cycle exercise in COPD. Eur Respir J 2008, 31:751-8.
• [33]Speranza L, Grilli A, Patruno A, Franceschelli S, Felzani G, Pesce M, Vinciguerra I, De Lutiis MA, Felaco M: Plasmatic markers of muscular stress in isokinetic exercise. J Biol Regul Homeost Agents 2007, 21:21-9.
• [34]Møller-Petersen J, Andersen PT, Hjørne N, Ditzel J: Hyperamylasemia, specific pancreatic enzymes, and hypoxanthine during recovery from diabetic ketoacidosis. Clin Chem 1985, 31:2001-4.
• [35]Puig JG, Mateos FA, Miranda ME, Torres RJ, De Miguel E, Pérez De Ayala C, Gil AA: Purine metabolism in women with primary gout. Am J Med 1994, 97:332-8.
• [36]Bianchi GP, Grossi G, Bargossi AM: May peripheral and central fatigue be correlated? Can we monitor them by means of clinical laboratory tools? J Sports Med Phys Fitness 1997, 37:194-9.
• [37]Steinberg JG, Delliaux S, Jammes Y: Reliability of different blood indices to explore the oxidative stress in response to maximal cycling and static exercises. Clin Physiol Funct Imaging 2006, 26:106-12.
• [38]Bloomer RJ, Goldfarb AH, Wideman L, McKenzie MJ, Consitt LA: Effects of acute aerobic and unaerobic exercise on blood markers of oxidative stress. J Strength Cond Res 2005, 19:276-85.
• [39]Uchiyama S, Tsukamoto H, Yoshimura S, Tamaki T: Relationship between oxidative stress in muscle tissue and weight-lifting-induced muscle damage. Pflugers Arch 2006, 452:109-16.
• [40]Hulbert AJ: On the importance of fatty acid composition of membranes for aging. J Theor Biol 2005, 234:277-88.
• [41]Vecchiet J, Cipollone F, Falasca K, Mezzetti A, Pizzigallo E, Bucciarelli T, De Laurentis S, Affaitati G, De Cesare D, Giamberardino MA: Relationship between musculoskeletal symptoms and blood markers of oxidative stress in patients with chronic fatigue syndrome. Neurosci Lett 2003, 335:151-4.
• [42]Deminice R, Sicchieri T, Payao PO, Jordao AA: Blood and salivary oxidative stress biomarkers following an acute session of resistence exercise in humans. Int J Sports Med 2010, 31:599-603.
• [43]Kawamoto EM, Vasconcelos AR, Degaspari S, Böhmer AE, Scavone C, Marcourakis T: Age-related changes in nitric oxide activity, cyclic GMP, and TBARS levels in platelets and erythrocytes reflect the oxidative status in central nervous system. Age (Dordr) 2012. in press.
• [44]Tan TY, Lu CH, Lin TK, Liou CW, Chuang YC, Schminke U: Factors associated with gender difference in the intima-media thickness of the common carotid artery. Clin Radiol 2009, 64:1097-103.
• [45]Groussard C, Rannou-Bekono F, Machefer G, Chevanne M, Vincent S, Sergent O, Cillard J, Gratas-Delamarche A: Changes in blood lipid peroxidation markers and antioxidants after a single sprint unaerobic exercise. Eur J Appl Physiol 2003, 89:14-20.
• [46]LaBella JJ, Daood MJ, Koretsky AP, Roman BB, Sieck GC, Wieringa B, Watchko JF: Absence of myofibrillar creatine kinase and diaphragm isometric function during repetitive activation. J Appl Physiol 1998, 84:1166-73.
• [47]Jammes Y, Steinberg JG, Delliaux S, Brégeon F: Chronic fatigue syndrome combines increased exercise-induced oxidative stress and reduced cytokine and Hsp responses. J Intern Med 2009, 266:196-206.
• [48]Ward WF, Qi W, Van Remmen H, Zackert WE, Roberts LJ 2nd, Richardson A: Effects of age and caloric restriction on lipid peroxidation: measurement of oxidative stress by F2-isoprostane levels. J Gerontol A Biol Sci Med Sci 2005, 60:847-51.
• [49]Basu S, Helmersson J, Jarosinska D, Sällsten G, Mazzolai B, Barregård L: Regulatory factors of basal F(2)-isoprostane formation: population, age, gender and smoking habits in humans. Free Radic Res 2009, 43:85-91.
• [50]Mastaloudis A, Leonard SW, Traber MG: Oxidative stress in athletes during extreme endurance exercise. Free Radic Biol Med 2001, 31:911-22.
• [51]Anderson NL, Anderson NG: The human plasma proteome: history, character, and diagnostic prospects. Mol Cell Proteomics 2002, 1:845-67.
• [52]Rajendiran S, Zachariah B, Hamide A: Increased protein carbonylation and decreased antioxidant status in anemic H. pylori infected patients: Effect of treatment. Saudi J Gastroenterol 2012, 18:252-6.
• [53]Jha R, Rizvi SI: Carbonyl formation in erythrocyte membrane proteins during aging in humans. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2011, 155:39-42.
• [54]Nanda N, Bobby Z, Hamide A: Oxidative stress and protein glycation in primary hypothyroidism. Male/female difference. Clin Exp Med 2008, 8:101-8.
• [55]Li G, Liu L, Hu H, Zhao Q, Xie F, Chen K, Liu S, Chen Y, Shi W, Yin D: Age-related carbonyl stress and erythrocyte membrane protein carbonylation. Clin Hemorheol Microcirc 2010, 46:305-11.
• [56]Radák Z, Ogonovszky H, Dubecz J, Pavlik G, Sasvari M, Pucsok J, Berkes I, Csont T, Ferdinandy P: Super-marathon race increases serum and urinary nitrotyrosine and carbonyl levels. Eur J Clin Invest 2003, 33:726-30.
• [57]Tiidus PM: Radical species in inflammation and overtraining. Can J Physiol Pharmacol 1998, 76:533-8.
• [58]Sen CK, Packer L: Thiol homeostasis and supplements in physical exercise. Am J Clin Nutr 2000, 72(suppl 2):653S-69S.
• [59]Cavalca V, Veglia F, Squellerio I, Marenzi G, Minardi F, De Metrio M, Cighetti G, Boccotti L, Ravagnani P, Tremoli E: Glutathione, vitamin E and oxidative stress in coronary artery disease: relevance of age and gender. Eur J Clin Invest 2009, 39:267-72.
• [60]Reid MB, Stokić DS, Koch SM, Khawli FA, Leis AA: N-acetylcysteine inhibits muscle fatigue in humans. J Clin Invest 1994, 94:2468-74.
• [61]Boya P, de la Peña A, Beloqui O, Larrea E, Conchillo M, Castelruiz Y, Civeira MP, Prieto J: Antioxidant status and glutathione metabolism in peripheral blood mononuclear cells from patients with chronic hepatitis C. J Hepatol 1999, 31:808-14.
• [62]Mendoza-Núñez VM, Ruiz-Ramos M, Sánchez-Rodríguez MA, Retana-Ugalde R, Muñoz-Sánchez JL: Aging-related oxidative stress in healthy humans. Tohoku J Exp Med 2007, 213:261-8.
• [63]Kamper EF, Chatzigeorgiou A, Tsimpoukidi O, Kamper M, Dalla C, Pitychoutis PM, Papadopoulou-Daifoti Z: Sex differences in oxidant/antioxidant balance under a chronic mild stress regime. Physiol Behav 2009, 98:215-22.
• [64]Palasuwan A, Suksom D, Margaritis I, Soogarun S, Rousseau AS: Effects of tai chi training on antioxidant capacity in pre- and postmenopausal women. J Aging Res 2011, 2011:234696.
• [65]Robertson JD, Maughan RJ, Duthie GG, Morrice PC: Increased blood antioxidant systems of runners in response to training load. Clin Sci (Lond) 1991, 80:611-8.
• [66]Sureda A, Tauler P, Aguiló A, Cases N, Fuentespina E, Córdova A, Tur JA, Pons A: Relation between oxidative stress markers and antioxidant endogenous defenses during exhaustive exercise. Free Radic Res 2005, 39:1317-24.
• [67]Vitai M, Góth L: Reference ranges of normal blood catalase activity and levels in familial hypocatalasemia in Hungary. Clin Chim Acta 1997, 261:35-42.
• [68]Pepe H, Balci SS, Revan S, Akalin PP, Kurtoğlu F: Comparison of oxidative stress and antioxidant capacity before and after running exercises in both sexes. Gend Med 2009, 6:587-95.
• [69]Rosety-Rodríguez M, Rosety M, Ordóñez FJ: Influence of regular exercise on erythrocyte catalase activity in adolescents with down syndrome. Med Clin (Barc) 2006, 127:533-4.
• [70]Mancuso M, Orsucci D, Logerfo A, Rocchi A, Petrozzi L, Nesti C, Galetta F, Santoro G, Murri L, Siciliano G: Oxidative stress biomarkers in mitochondrial myopathies, basally and after cysteine donor supplementation. J Neurol 2010, 257:774-81.
• [71]Leelarungrayub D, Khansuwan R, Pothongsunun P, Klaphajone J: N-acetylcysteine supplementation controls total antioxidant capacity, creatine kinase, lactate, nd tumor necrotic factor-alpha against oxidative stress induced by graded exercise in sedentary men. Oxid Med Cell Longev 2011, 2011:329643.
• [72]Pandey KB, Mehdi MM, Maurya PK, Rizvi SI: Plasma protein oxidation and its correlation with antioxidant potential during human aging. Dis Markers 2010, 29:31-6.
• [73]Woo J, Leung SS, Lam CW, Ho SC, Lam TH, Janus ED: Plasma total antioxidant capacity in an adult Hong Kong Chinese population. Clin Biochem 1997, 30:553-7.
• [74]Kanter MM, Nolte LA, Holloszy JO: Effects of an antioxidant vitamin mixture on lipid peroxidation at rest and postexercise. J Appl Physiol 1993, 74:965-9.
• [75]Balakrishnan SD, Anuradha CV: Exercise, depletion of antioxidants and antioxidant manipulation. Cell Biochem Funct 1998, 16:269-75.
• [76]Wood LJ, Nail LM, Winters KA: Does muscle-derived interleukin-6 mediate some of the beneficial effects of exercise on cancer treatment-related fatigue? Oncol Nurs Forum 2009, 36:519-24.
• [77]Simpson RJ, Florida-James GD, Whyte GP, Guy K: The effects of intensive, moderate and downhill treadmill running on human blood lymphocytes expressing the adhesion/activation molecules CD54 (ICAM-1), CD18 (beta2 integrin) and CD53. Eur J Appl Physiol 2006, 97:109-21.
• [78]Stulnig T, Maczek C, Böck G, Majdic O, Wick G: Reference intervals for human peripheral blood lymphocyte subpopulations from 'healthy' young and aged subjects. Int Arch Allergy Immunol 1995, 108:205-10.
• [79]Goetzl EJ, Huang MC, Kon J, Patel K, Schwartz JB, Fast K, Ferrucci L, Madara K, Taub DD, Longo DL: Gender specificity of altered human immune cytokine profiles in aging. FASEB J 2010, 24:3580-9.
• [80]Foster AD, Soloviova K, Puliaeva I, Puliaiev M, Puliaev R, Finkelman F, Via CS: Donor CD8 T cells and IFN-gamma are critical for sex-based differences in donor CD4 T cell engraftment and lupus-like phenotype in short-term chronic graft-versus-host disease mice. J Immunol 2011, 186:6238-54.
• [81]De Fanis U, Wang GC, Fedarko NS, Walston JD, Casolaro V, Leng SX: T-lymphocytes expressing CC chemokine receptor-5 are increased in frail older adults. J Am Geriatr Soc 2008, 56:904-8.
• [82]Pedersen BK, Akerström TC, Nielsen AR, Fischer CP: Role of myokines in exercise and metabolism. J Appl Physiol 2007, 103:1093-8.
• [83]Febbraio MA, Pedersen BK: Contraction-induced myokine production and release: is skeletal muscle an endocrine organ? Exerc Sport Sci Rev 2005, 33:114-9.
• [84]Robson-Ansley P, Barwood M, Eglin C, Ansley L: The effect of carbohydrate ingestion on the interleukin-6 response to a 90-minute run time trial. Int J Sports Physiol Perform 2009, 4:186-94.
• [85]Petersen AM, Pedersen BK: The anti-inflammatory effect of exercise. J Appl Physiol 2005, 98:1154-62.
• [86]Sun A, Wang YP, Chia JS, Liu BY, Chiang CP: Treatment with levamisole and colchicine can result in a significant reduction of IL-6, IL-8 or TNF-alpha level in patients with mucocutaneous type of Behcet's disease. J Oral Pathol Med 2009, 38:401-5.
• [87]Minetto MA, Gazzoni M, Lanfranco F, Baldi M, Saba L, Pedrola R, Komi PV, Rainoldi A: Influence of the sample collection method on salivary interleukin-6 levels in resting and post-exercise conditions. Eur J Appl Physiol 2007, 101:249-56.
• [88]Robson-Ansley PJ, Blannin A, Gleeson M: Elevated plasma interleukin-6 levels in trained male triathletes following an acute period of intense interval training. Eur J Appl Physiol 2007, 99:353-60.
• [89]Bautmans I, Njemini R, Predom H, Lemper JC, Mets T: Muscle endurance in elderly nursing home residents is related to fatigue perception, mobility, and circulating tumor necrosis factor-, interleukin-6, and heat shock protein 70. J Am Geriatr Soc 2008, 56:389-96.
• [90]Bermudez DM, Canning DA, Liechty KW: Age and pro-inflammatory cytokine production: wound-healing implications for scar-formation and the timing of genital surgery in boys. J Pediatr Urol 2011, 7:324-31.
• [91]Vernon SD, Nicholson A, Rajeevan M, Dimulescu I, Cameron B, Whistler T, Lloyd A: Correlation of psycho-neuroendocrine-immune (PNI) gene expression with symptoms of acute infectious mononucleosis. Brain Res 2006, 1068:1-6.
• [92]Light AR, White AT, Hughen RW, Light KC: Moderate exercise increases expression for sensory, adrenergic, and immune genes in chronic fatigue syndrome patients but not in normal subjects. J Pain 2009, 10:1099-112.
• [93]Gusba JE, Wilson RJ, Robinson DL, Graham TE: Interleukin-6 and its mRNA responses in exercise and recovery: relationship to muscle glycogen. Scand J Med Sci Sports 2008, 18:77-85.
• [94]Witko-Sarsat V, Friedlander M, Capeillère-Blandin C, Nguyen-Khoa T, Nguyen AT, Zingraff J, Jungers P, Descamps-Latscha B: Advanced oxidation protein products as a novel marker of oxidative stress in uremia. Kidney Int 1996, 49:1304-13.
• [95]Nijs J, Van Oosterwijck J, Meeus M, Lambrecht L, Metzger K, Frémont M, Paul L: Unravelling the nature of postexertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: the role of elastase, complement C4a and interleukin-1beta. J Intern Med 2010, 267:418-35.
• [96]Finsterer J, Milvay E: Stress lactate in mitochondrial myopathy under constant, unadjusted workload. Eur J Neurol 2004, 11:811-6.
• [97]Jeppesen TD, Olsen D, Vissing J: Cycle ergometry is not a sensitive diagnostic test for mitochondrial myopathy. J Neurol 2003, 250:293-9.