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The Potential Role of Exercise-Induced Muscle Damage in Exertional Heat Stroke

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Abstract

Exertional heat stroke (EHS) is a life-threatening condition that affects mainly athletes, military personnel, firefighters, and occupational workers. EHS is frequently observed in non-compensable conditions (where the body is unable to maintain a steady thermal balance) as a result of heavy heat stress and muscle contraction associated with prolonged and strenuous physical and occupational activities, resulting in central nervous system dysfunction followed by multi-organ damage and failure. Since the pathophysiology of EHS is complex and involves multiple organs and systems, any condition that changes the interrelated systems may increase the risk for EHS. It has been suggested that exercise-induced muscle damage (EIMD) can lead to thermoregulatory impairment and systemic inflammation, which could be a potential predisposing factor for EHS. In this review article, we aim to (1) address the evidence of EIMD as a predisposing factor for EHS and (2) propose a possible mechanism of how performing muscle-damaging exercise in the heat may aggravate muscle damage and subsequent risk of EHS and acute kidney injury (AKI). Such an understanding could be meaningful to minimize the risks of EHS and AKI for individuals with muscle damage due to engaging in physical work in hot environments.

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References

  1. Update: heat illness, active component, US armed forces, 2018. MSMR. 2019;26:15–20.

  2. Maron BJ, Haas TS, Ahluwalia A, Murphy CJ, Garberich RF. Demographics and epidemiology of sudden deaths in young competitive athletes: from the United States National Registry. Am J Med. 2016;129:1170–7.

    Article  PubMed  Google Scholar 

  3. Bonauto D, Anderson R, Rauser E, Burke B. Occupational heat illness in Washington State, 1995–2005. Am J Ind Med. 2007;50:940–50.

    Article  PubMed  Google Scholar 

  4. Armstrong LE, Casa DJ, Millard-Stafford M, Moran DS, Pyne SW, Roberts WO. Exertional heat illness during training and competition. Med Sci Sports Exerc. 2007;39:556–72.

    Article  PubMed  Google Scholar 

  5. Muldoon S, Deuster P, Voelkel M, Capacchione J, Bunger R. Exertional heat illness, exertional rhabdomyolysis, and malignant hyperthermia: is there a link? Curr Sports Med Rep. 2008;7:74–80.

    Article  PubMed  Google Scholar 

  6. Fortes MB, Di Felice U, Dolci A, Junglee NA, Crockford MJ, West L, et al. Muscle-damaging exercise increases heat strain during subsequent exercise heat stress. Med Sci Sports Exerc. 2013;45:1915–24.

    Article  CAS  PubMed  Google Scholar 

  7. Montain SJ, Latzka WA, Sawka MN. Impact of muscle injury and accompanying inflammatory response on thermoregulation during exercise in the heat. J Appl Physiol. 2000;89:1123–30.

    Article  CAS  PubMed  Google Scholar 

  8. Junglee NA, Di Felice U, Dolci A, Fortes MB, Jibani MM, Lemmey AB, et al. Exercising in a hot environment with muscle damage: effects on acute kidney injury biomarkers and kidney function. Am J Physiol-Ren Physiol. 2013;305:F813–20.

    Article  CAS  Google Scholar 

  9. Sawka MN, Leon LR, Montain SJ, Sonna LA. Integrated physiological mechanisms of exercise performance, adaptation, and maladaptation to heat stress. Compr Physiol. 2011;1(4):1883–928.

    Article  PubMed  Google Scholar 

  10. Leon LR, Bouchama A. Heat stroke. Compr Physiol. 2015;5:611–47.

    Article  Google Scholar 

  11. Kenny GP, Reardon FD, Thoden JS, Giesbrecht GG, Kenny G. Changes in exercise and post-exercise core temperature under different clothing conditions. Int J Biometeorol. 1999;43:8–13.

    Article  CAS  PubMed  Google Scholar 

  12. Wang L, Yin H, Di Y, Liu Y, Liu J. Human local and total heat losses in different temperature. Physiol Behav. 2016;157:270–6.

    Article  CAS  PubMed  Google Scholar 

  13. Notley SR, Poirier MP, Hardcastle SG, Flouris AD, Boulay P, Sigal RJ, et al. Aging impairs whole-body heat loss in women under both dry and humid heat stress. Med Sci Sports Exerc. 2017;49:2324–32.

    Article  PubMed  Google Scholar 

  14. Epstein Y, Roberts WO. The pathopysiology of heat stroke: an integrative view of the final common pathway. Scand J Med Sci Sports. 2011;21:742–8.

    Article  CAS  PubMed  Google Scholar 

  15. Giercksky T, Boberg KM, Farstad IN, Halvorsen S. Severe liver failure in exertional heat stroke. Scand J Gastroenterol. 1999;34:824–7.

    Article  CAS  PubMed  Google Scholar 

  16. Morrissey MC, Szymanski MR, Grundstein AJ, Casa DJ. New perspectives on risk factors for exertional heat stroke. Kinesiol Rev. 2020;9:64–71.

    Article  Google Scholar 

  17. Piver WT, Ando M, Ye F, Portier CJ. Temperature and air pollution as risk factors for heat stroke in Tokyo, July and August 1980–1995. Environ Health Perspect. 1999;107:911–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Neas LM, Dockery DW, Ware JH, Spengler JD, Speizer FE, Ferris BG. Association of indoor nitrogen dioxide with respiratory symptoms and pulmonary function in children. Am J Epidemiol. 1991;134:204–19.

    Article  CAS  PubMed  Google Scholar 

  19. Shibolet S, Coll R, Gilat T, Sohar E. Heatstroke: its clinical picture and mechanism in 36 cases. Q J Med. 1967;36:525–48.

    CAS  PubMed  Google Scholar 

  20. Laitano O, Leon LR, Roberts WO, Sawka MN. Controversies in exertional heat stroke diagnosis, prevention, and treatment. J Appl Physiol. 2019;127:1338–48.

    Article  CAS  PubMed  Google Scholar 

  21. Carter R, Cheuvront SN, Sawka MN. A case report of idiosyncratic hyperthermia and review of US army heat stroke hospitalizations. J Sport Rehabil. 2007;16:238–43.

    Article  PubMed  Google Scholar 

  22. Westwood CS, Fallowfield JL, Delves SK, Nunns M, Ogden HB, Layden JD. Individual risk factors associated with exertional heat illness: a systematic review. Exp Physiol. 2021;106(1):191–9.

    Article  PubMed  Google Scholar 

  23. Armstrong RB, Warren GL, Warren JA. Mechanisms of exercise-induced muscle fibre injury. Sports Med. 1991;12:184–207.

    Article  CAS  PubMed  Google Scholar 

  24. Enoka RM. Eccentric contractions require unique activation strategies by the nervous system. J Appl Physiol. 1996;81:2339–46.

    Article  CAS  PubMed  Google Scholar 

  25. Fridén J, Sjöström M, Ekblom B. Myofibrillar damage following intense eccentric exercise in man. Int J Sports Med. 1983;04:170–6.

    Article  Google Scholar 

  26. Tiidus PM. Skeletal muscle damage and repair. Chicago: Human Kinetics; 2008.

    Book  Google Scholar 

  27. Eston RG, Finney S, Baker S, Baltzopoulos V. Muscle tenderness and peak torque changes after downhill running following a prior bout of isokinetic eccentric exercise. J Sports Sci. 1996;14:291–9.

    Article  CAS  PubMed  Google Scholar 

  28. Lima LCR, Nosaka K, Chen TC, Pinto RS, Greco CC, Denadai BS. Decreased running economy is not associated with decreased force production capacity following downhill running in untrained, young men. Eur J Sport Sci. 2020;0:1–9.

    Google Scholar 

  29. Gibala MJ, MacDougall JD, Tarnopolsky MA, Stauber WT, Elorriaga A. Changes in human skeletal muscle ultrastructure and force production after acute resistance exercise. J Appl Physiol. 1995;78:702–8.

    Article  CAS  PubMed  Google Scholar 

  30. Nosaka K, Clarkson PM, McGuiggin ME, Byrne JM. Time course of muscle adaptation after high force eccentric exercise. Eur J Appl Physiol. 1991;63:70–6.

    Article  CAS  Google Scholar 

  31. Saxton JM, Clarkson PM, James R, Miles M, Westerfer M, Clark S, et al. Neuromuscular dysfunction following eccentric exercise. Med Sci Sports Exerc. 1995;27:1185–93.

    Article  CAS  PubMed  Google Scholar 

  32. Warren GL, Lowe DA, Armstrong RB. Measurement tools used in the study of eccentric contraction-induced injury. Sports Med Auckl NZ. 1999;27:43–59.

    Article  CAS  Google Scholar 

  33. Peake JM, Suzuki K, Wilson G, Hordern M, Nosaka K, Mackinnon L, et al. Exercise-induced muscle damage, plasma cytokines, and markers of neutrophil activation. Med Sci Sports Exerc. 2005;37:737–45.

    Article  CAS  PubMed  Google Scholar 

  34. Mauro A. Satellite cell of skeletal muscle fibers. J Biophys Biochem Cytol. 1961;9:493–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Sciorati C, Rigamonti E, Manfredi AA, Rovere-Querini P. Cell death, clearance and immunity in the skeletal muscle. Cell Death Differ. 2016;23:927–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Clarkson PM, Hubal MJ. Exercise-induced muscle damage in humans. Am J Phys Med Rehabil. 2002;81:S52-69.

    Article  PubMed  Google Scholar 

  37. Toumi H, Best TM. The inflammatory response: friend or enemy for muscle injury? Br J Sports Med. 2003;37:284–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Fielding RA, Manfredi TJ, Ding W, Fiatarone MA, Evans WJ, Cannon JG. Acute phase response in exercise. III. Neutrophil and IL-1 beta accumulation in skeletal muscle. Am J Physiol-Regul Integr Comp Physiol. 1993;265:R166–72.

    Article  CAS  Google Scholar 

  39. Cannon JG, Fielding RA, Fiatarone MA, Orencole SF, Dinarello CA, Evans WJ. Increased interleukin 1 beta in human skeletal muscle after exercise. Am J Physiol Regul Integr Comp Physiol. 1989;257:R451–5.

    Article  CAS  Google Scholar 

  40. Bruunsgaard H, Galbo H, Halkjaer-Kristensen J, Johansen TL, MacLean DA, Pedersen BK. Exercise-induced increase in serum interleukin-6 in humans is related to muscle damage. J Physiol. 1997;499(Pt 3):833–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Hellsten Y, Frandsen U, Orthenblad N, Sjødin B, Richter EA. Xanthine oxidase in human skeletal muscle following eccentric exercise: a role in inflammation. J Physiol. 1997;498:239–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Toft AD, Jensen LB, Bruunsgaard H, Ibfelt T, Halkjær-Kristensen J, Febbraio M, et al. Cytokine response to eccentric exercise in young and elderly humans. Am J Physiol-Cell Physiol. 2002;283:C289–95.

    Article  CAS  PubMed  Google Scholar 

  43. Ostrowski K, Rohde T, Zacho M, Asp S, Pedersen BK. Evidence that IL-6 is produced in skeletal muscle during intense long-term muscle activity. J Physiol Lond. 1998;508:949–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Camus G, Poortmans J, Nys M, Deby-Dupont G, Duchateau J, Deby C, et al. Mild endotoxaemia and the inflammatory response induced by a marathon race. Clin Sci. 1997;92:415–22.

    Article  CAS  Google Scholar 

  45. Pyne DB. Exercise-induced muscle damage and inflammation: a review. Aust J Sci Med Sport. 1994;26:49–49.

    CAS  PubMed  Google Scholar 

  46. Malm C. Exercise-induced muscle damage and inflammation: fact or fiction? Acta Physiol Scand. 2001;171:233–9.

    Article  CAS  PubMed  Google Scholar 

  47. Child R, Brown S, Day S, Donnelly A, Roper H, Saxton J. Changes in indices of antioxidant status, lipid peroxidation and inflammation in human skeletal muscle after eccentric muscle actions. Clin Sci. 1998;96:105–15.

    Article  Google Scholar 

  48. Bäcker HC, Busko M, Krause FG, Exadaktylos AK, Klukowska-Roetzler J, Deml MC. Exertional rhabdomyolysis and causes of elevation of creatine kinase. Phys Sportsmed. 2020;48(2):179–85.

    Article  PubMed  Google Scholar 

  49. Milne CJ. Rhabdomyolysis, myoglobinuria and exercise. Sports Med. 1988;6:93–106.

    Article  CAS  PubMed  Google Scholar 

  50. Patel DR, Gyamfi R, Torres A. Exertional rhabdomyolysis and acute kidney injury. Phys Sportsmed. 2009;37:71–9.

    Article  PubMed  Google Scholar 

  51. Carter R, Cheuvront SN, Williams JO, Kolka MA, Stephenson LA, Sawka MN, et al. Epidemiology of hospitalizations and deaths from heat illness in soldiers. Med Sci Sports Exerc. 2005;37:1338–44.

    Article  PubMed  Google Scholar 

  52. Kim J, Lee J, Kim S, Ryu HY, Cha KS, Sung DJ. Exercise-induced rhabdomyolysis mechanisms and prevention: a literature review. J Sport Health Sci. 2016;5:324–33.

    Article  PubMed  Google Scholar 

  53. Tietze DC, Borchers J. Exertional rhabdomyolysis in the athlete: a clinical review. Sports Health. 2014;6:336–9.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Ward MM. Factors predictive of acute renal failure in rhabdomyolysis. Arch Intern Med. 1988;148:1553–7.

    Article  CAS  PubMed  Google Scholar 

  55. Abriat A, Brosset C, Brégigeon M, Sagui E. Report of 182 cases of exertional heatstroke in the French Armed Forces. Mil Med. 2014;179:309–14.

    Article  PubMed  Google Scholar 

  56. Premru V, Kovač J, Ponikvar R. Use of myoglobin as a marker and predictor in myoglobinuric acute kidney injury. Ther Apher Dial. 2013;17:391–5.

    Article  CAS  PubMed  Google Scholar 

  57. Molitoris BA, Sandoval R, Sutton TA. Endothelial injury and dysfunction in ischemic acute renal failure. Crit Care Med. 2002;30:S235.

    Article  PubMed  Google Scholar 

  58. Bosch X, Poch E, Grau JM. Rhabdomyolysis and acute kidney injury. N Engl J Med. 2009;361:62–72.

    Article  CAS  PubMed  Google Scholar 

  59. Trujillo MH, Fragachán GC. Rhabdomyolysis and acute kidney injury due to severe heat stroke. Case Rep Crit Care. 2011;e951719.

  60. Holt S, Moore K. Pathogenesis of renal failure in rhabdomyolysis: the role of myoglobin. Nephron Exp Nephrol. 2000;8:72–6.

    Article  CAS  Google Scholar 

  61. Clarkson PM, Kearns AK, Rouzier P, Rubin R, Thompson PD. Serum creatine kinase levels and renal function measures in exertional muscle damage. Med Sci Sports Exerc. 2006;38:623.

    Article  CAS  PubMed  Google Scholar 

  62. Furman J. When exercise causes exertional rhabdomyolysis. J Am Acad PAs. 2015;28:38–43.

    Google Scholar 

  63. Knochel JP. Rhabdomyolysis and myoglobinuria. Annu Rev Med. 1982;33:435–43.

    Article  CAS  PubMed  Google Scholar 

  64. Chapman CL, Johnson BD, Vargas NT, Hostler D, Parker MD, Schlader ZJ. Both hyperthermia and dehydration during physical work in the heat contribute to the risk of acute kidney injury. J Appl Physiol. 2020;128:715–28.

    Article  CAS  PubMed  Google Scholar 

  65. Bischof JC, Padanilam J, Holmes WH, Ezzell RM, Lee RC, Tompkins RG, et al. Dynamics of cell membrane permeability changes at supraphysiological temperatures. Biophys J. 1995;68:2608–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Dinarello CA. Cytokines as endogenous pyrogens. J Infect Dis. 1999;179:S294-304.

    Article  CAS  PubMed  Google Scholar 

  67. Netea MG, Kullberg BJ, Van der Meer JWM. Circulating cytokines as mediators of fever. Clin Infect Dis. 2000;31:S178–84.

    Article  CAS  PubMed  Google Scholar 

  68. Saper CB, Breder CD. The neurologic basis of fever. N Engl J Med. 1994;330:1880–6.

    Article  CAS  PubMed  Google Scholar 

  69. Keuter M, Dharmana E, Kullberg B-J, Schalkwijk C, Gasem MH, Seuren L, et al. Phospholipase A2 is a circulating mediator in typhoid fever. J Infect Dis. 1995;172:305–8.

    Article  CAS  PubMed  Google Scholar 

  70. Lepock JR, Cheng K-H, Al-Qysi H, Kruuv J. Thermotropic lipid and protein transitions in Chinese hamster lung cell membranes: relationship to hyperthermic cell killing. Can J Biochem Cell Biol. 1983;61:421–7.

    Article  CAS  PubMed  Google Scholar 

  71. Lepock JR, Cheng K-H, Al-qysi H, Sim I, Koch CJ, Kruuv J. Hyperthermia-induced inhibition of respiration and mitochondrial protein denaturation in CHL cells. Int J Hyperth. 1987;3:123–32.

    Article  CAS  Google Scholar 

  72. Febbraio MA, Snow RJ, Stathis CG, Hargreaves M, Carey MF. Effect of heat stress on muscle energy metabolism during exercise. J Appl Physiol. 1994;77:2827–31.

    Article  CAS  PubMed  Google Scholar 

  73. Febbraio MA, Snow RJ, Hargreaves M, Stathis CG, Martin IK, Carey MF. Muscle metabolism during exercise and heat stress in trained men: effect of acclimation. J Appl Physiol. 1994;76:589–97.

    Article  CAS  PubMed  Google Scholar 

  74. Castellani JW, Zambraski EJ, Sawka MN, Urso ML. Does high muscle temperature accentuate skeletal muscle injury from eccentric exercise? Physiol Rep. 2016;4:e12777.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Cleary MA, Sweeney LA, Kendrick ZV, Sitler MR. Dehydration and symptoms of delayed-onset muscle soreness in hyperthermic males. J Athl Train. 2005;40:288–97.

    PubMed  PubMed Central  Google Scholar 

  76. Lembke P, Capodice J, Hebert K, Swenson T. Influence of omega-3 (N3) index on performance and wellbeing in young adults after heavy eccentric exercise. J Sports Sci Med. 2014;13:151–6.

    PubMed  PubMed Central  Google Scholar 

  77. Hurley CF, Hatfield DL, Riebe DA. The effect of caffeine ingestion on delayed onset muscle soreness. J Strength Cond Res. 2013;27:3101–9.

    Article  PubMed  Google Scholar 

  78. Ra S-G, Miyazaki T, Ishikura K, Nagayama H, Komine S, Nakata Y, et al. Combined effect of branched-chain amino acids and taurine supplementation on delayed onset muscle soreness and muscle damage in high-intensity eccentric exercise. J Int Soc Sports Nutr. 2013;10:51.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Trombold JR, Barnes JN, Critchley L, Coyle EF. Ellagitannin consumption improves strength recovery 2–3 d after eccentric exercise. Med Sci Sports Exerc. 2010;42:493–8.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Health, Exercise and Sport Sciences, University of New Mexico, Albuquerque, NM, USA

    Zidong Li, Zachary J. McKenna, Christine M. Mermier & Fabiano T. Amorim

  2. Department of Exercise Science, High Point University, High Point, NC, USA

    Matthew R. Kuennen

  3. Department of Physical Education, Universidade Federal dos Vales do Jequitinhonha e Mucuri, Diamantina, Minas Gerais, Brazil

    Flávio de Castro Magalhães

  4. Department of Health and Human Performance, Northwestern State University, Natchitoches, LA, USA

    Zidong Li

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Correspondence to Zidong Li.

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Zidong Li, Zachary McKenna, Matthew Kuennen, Flavio de Castro Magalhaes, Christine Mermier, and Fabiano Amorim declare that they have no conflicts of interest relevant to the content of this review.

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ZL and FA wrote the first draft of the manuscript. ZM and FA made the graphs; ZM, MK, FCM, CM, and FA revised the original manuscript. All authors read and approved the final manuscript.

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Li, Z., McKenna, Z.J., Kuennen, M.R. et al. The Potential Role of Exercise-Induced Muscle Damage in Exertional Heat Stroke. Sports Med 51, 863–872 (2021). https://doi.org/10.1007/s40279-021-01427-8

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