Int J Sports Med
DOI: 10.1055/a-2251-3170
Physiology & Biochemistry

Implications of Heat Stress-induced Metabolic Alterations for Endurance Training

Samuel Bennett
1   Center for Biological Clocks Research, Texas A&M University, College Station, United States
,
Eve Tiollier
2   Laboratory Sport, Expertise and Performance, Research Department, Institut National du Sport de l'Expertise et de la Performance, Paris, France
,
Daniel J. Owens
3   Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, United Kingdom of Great Britain and Northern Ireland
,
Franck Brocherie
2   Laboratory Sport, Expertise and Performance, Research Department, Institut National du Sport de l'Expertise et de la Performance, Paris, France
,
Julien B. Louis
2   Laboratory Sport, Expertise and Performance, Research Department, Institut National du Sport de l'Expertise et de la Performance, Paris, France
3   Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, United Kingdom of Great Britain and Northern Ireland
› Author Affiliations

Abstract

Inducing a heat-acclimated phenotype via repeated heat stress improves exercise capacity and reduces athletes̓ risk of hyperthermia and heat illness. Given the increased number of international sporting events hosted in countries with warmer climates, heat acclimation strategies are increasingly popular among endurance athletes to optimize performance in hot environments. At the tissue level, completing endurance exercise under heat stress may augment endurance training adaptation, including mitochondrial and cardiovascular remodeling due to increased perturbations to cellular homeostasis as a consequence of metabolic and cardiovascular load, and this may improve endurance training adaptation and subsequent performance. This review provides an up-to-date overview of the metabolic impact of heat stress during endurance exercise, including proposed underlying mechanisms of altered substrate utilization. Against this metabolic backdrop, the current literature highlighting the role of heat stress in augmenting training adaptation and subsequent endurance performance will be presented with practical implications and opportunities for future research.



Publication History

Received: 26 August 2023

Accepted: 15 January 2024

Article published online:
24 February 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Nybo L, Nielsen B. Perceived exertion is associated with an altered brain activity during exercise with progressive hyperthermia. J Appl Physiol (1985) 2001; 91: 2017-2023
  • 2 Rowell LB. Human cardiovascular adjustments to exercise and thermal stress. Physiol Rev 1974; 54: 75-159
  • 3 Febbraio MA, Snow RJ, Hargreaves M. et al. Muscle metabolism during exercise and heat stress in trained men: Effect of acclimation. J Appl Physiol (1985) 1994; 76: 589-597
  • 4 Gonzalez-Alonso J, Mora-Rodriguez R, Coyle EF. Stroke volume during exercise: Interaction of environment and hydration. Am J Physiol Heart Circ Physiol 2000; 278: H321-330
  • 5 Febbraio MA. Alterations in energy metabolism during exercise and heat stress. Sports Med 2001; 31: 47-59
  • 6 Nybo L, Rasmussen P, Sawka MN. Performance in the heat-physiological factors of importance for hyperthermia-induced fatigue. Compr Physiol 2014; 4: 657-689
  • 7 Burke LM. Nutritional needs for exercise in the heat. Comp Biochem Physiol A Mol Integr Physiol 2001; 128: 735-748
  • 8 El Helou N, Tafflet M, Berthelot G. et al. Impact of environmental parameters on marathon running performance. PLoS One 2012; 7: e37407
  • 9 Periard JD, Racinais S, Sawka MN. Adaptations and mechanisms of human heat acclimation: Applications for competitive athletes and sports. Scand J Med Sci Sports 2015; 25: 20-38
  • 10 Hawley JA, Lundby C, Cotter JD. et al. Maximizing Cellular Adaptation to Endurance Exercise in Skeletal Muscle. Cell Metab 2018; 27: 962-976
  • 11 Febbraio MA, Snow RJ, Stathis CG. et al. Effect of heat stress on muscle energy metabolism during exercise. J Appl Physiol (1985) 1994; 77: 2827-2831
  • 12 Hargreaves M, Dillo P, Angus D. et al. Effect of fluid ingestion on muscle metabolism during prolonged exercise. J Appl Physiol (1985) 1996; 80: 363-366
  • 13 Parkin JM, Carey MF, Zhao S. et al. Effect of ambient temperature on human skeletal muscle metabolism during fatiguing submaximal exercise. J Appl Physiol (1985) 1999; 86: 902-908
  • 14 Febbraio MA, Carey MF, Snow RJ. et al. Influence of elevated muscle temperature on metabolism during intense, dynamic exercise. Am J Physiol 1996; 271: R1251-1255
  • 15 Young AJ, Sawka MN, Levine L. et al. Metabolic and thermal adaptations from endurance training in hot or cold water. J Appl Physiol (1985) 1995; 78: 793-801
  • 16 Dolny DG, Lemon PW. Effect of ambient temperature on protein breakdown during prolonged exercise. J Appl Physiol (1985) 1988; 64: 550-555
  • 17 Febbraio MA, Murton P, Selig SE. et al. Effect of CHO ingestion on exercise metabolism and performance in different ambient temperatures. Med Sci Sports Exerc 1996; 28: 1380-1387
  • 18 Fernandez-Elias VE, Hamouti N, Ortega JF. et al. Hyperthermia, but not muscle water deficit, increases glycogen use during intense exercise. Scand J Med Sci Sports 2015; 25: 126-134
  • 19 Galloway SD, Maughan RJ. Effects of ambient temperature on the capacity to perform prolonged cycle exercise in man. Med Sci Sports Exerc 1997; 29: 1240-1249
  • 20 Hargreaves M, Angus D, Howlett K. et al. Effect of heat stress on glucose kinetics during exercise. J Appl Physiol (1985) 1996; 81: 1594-1597
  • 21 Yaspelkis BB, Scroop GC, Wilmore KM. et al. Carbohydrate metabolism during exercise in hot and thermoneutral environments. Int J Sports Med 1993; 14: 13-19
  • 22 Young AJ. Energy substrate utilization during exercise in extreme environments. Exerc Sport Sci Rev 1990; 18: 65-117
  • 23 Hettinga FJ, De Koning JJ, de Vrijer A. et al. The effect of ambient temperature on gross-efficiency in cycling. Eur J Appl Physiol 2007; 101: 465-471
  • 24 Jentjens RL, Underwood K, Achten J. et al. Exogenous carbohydrate oxidation rates are elevated after combined ingestion of glucose and fructose during exercise in the heat. J Appl Physiol (1985) 2006; 100: 807-816
  • 25 Jentjens RL, Wagenmakers AJ, Jeukendrup AE. Heat stress increases muscle glycogen use but reduces the oxidation of ingested carbohydrates during exercise. J Appl Physiol (1985) 2002; 92: 1562-1572
  • 26 Marino FE, Mbambo Z, Kortekaas E. et al. Influence of ambient temperature on plasma ammonia and lactate accumulation during prolonged submaximal and self-paced running. Eur J Appl Physiol 2001; 86: 71-78
  • 27 Young AJ, Sawka MN, Levine L. et al. Skeletal muscle metabolism during exercise is influenced by heat acclimation. J Appl Physiol (1985) 1985; 59: 1929-1935
  • 28 Maxwell NS, Gardner F, Nimmo MA. Intermittent running: Muscle metabolism in the heat and effect of hypohydration. Med Sci Sports Exerc 1999; 31: 675-683
  • 29 Nielsen B, Savard G, Richter EA. et al. Muscle blood flow and muscle metabolism during exercise and heat stress. J Appl Physiol (1985) 1990; 69: 1040-1046
  • 30 Boynton JR, Danner F, Menaspa P. et al. Effect of Environmental Temperature on High-Intensity Intervals in Well-Trained Cyclists. Int J Sports Physiol Perform 2019; DOI: 10.1123/ijspp.2018-0689:. 1-7
  • 31 Lorenzo S, Halliwill JR, Sawka MN. et al. Heat acclimation improves exercise performance. J Appl Physiol (1985) 2010; 109: 1140-1147
  • 32 Maunder E, Plews DJ, Merien F. et al. Stability of Heart Rate at Physiological Thresholds Between Temperate and Heat Stress Environments in Endurance-Trained Males. Int J Sports Physiol Perform 2021; 16: 1204-1207
  • 33 Maunder E, Plews DJ, Wallis GA. et al. Temperate performance and metabolic adaptations following endurance training performed under environmental heat stress. Physiol Rep 2021; 9: e14849
  • 34 Charoensap T, Kilding AE, Maunder E. Carbohydrate, but not fat, oxidation is reduced during moderate-intensity exercise performed in 33 vs. 18 degrees C at matched heart rates. Eur J Appl Physiol 2023; 123: 2073-2085
  • 35 Maunder E, Plews DJ, Merien F. et al. Exercise intensity regulates the effect of heat stress on substrate oxidation rates during exercise. Eur J Sport Sci 2020; 20: 935-943
  • 36 Lucia A, Hoyos J, Carvajal A. et al. Heart rate response to professional road cycling: The Tour de France. Int J Sports Med 1999; 20: 167-172
  • 37 Corbett J, Massey HC, Costello JT. et al. The effect of medium-term heat acclimation on endurance performance in a temperate environment. Eur J Sport Sci 2022; 22: 190-199
  • 38 Yamada PM, Amorim FT, Moseley P. et al. Effect of heat acclimation on heat shock protein 72 and interleukin-10 in humans. J Appl Physiol (1985) 2007; 103: 1196-1204
  • 39 Snow RJ, Febbraio MA, Carey MF. et al. Heat stress increases ammonia accumulation during exercise in humans. Exp Physiol 1993; 78: 847-850
  • 40 Graham TE, MacLean DA. Ammonia and amino acid metabolism in human skeletal muscle during exercise. Can J Physiol Pharmacol 1992; 70: 132-141
  • 41 Bennett S, Brocherie F, Phelan MM. et al. Acute heat stress amplifies exercise-induced metabolomic perturbations and reveals variation in circulating amino acids in endurance-trained males. Exp Physiol 2023; 108: 838-851
  • 42 Williams BD, Chinkes DL, Wolfe RR. Alanine and glutamine kinetics at rest and during exercise in humans. Med Sci Sport Exer 1998; 30: 1053-1058
  • 43 Hoffman NJ. Omics and Exercise: Global Approaches for Mapping Exercise Biological Networks. Cold Spring Harb Perspect Med 2017; 7: a029884
  • 44 Burniston JG, Chen YW. Omics Approaches to Understanding Muscle Biology. Berlin, Germany: Springer; 2019
  • 45 Belhaj MR, Lawler NG, Hoffman NJ. Metabolomics and Lipidomics: Expanding the Molecular Landscape of Exercise Biology. Metabolites 2021; 11: 151
  • 46 King DS, Costill DL, Fink WJ. et al. Muscle metabolism during exercise in the heat in unacclimatized and acclimatized humans. J Appl Physiol (1985) 1985; 59: 1350-1354
  • 47 Kozlowski S, Brzezinska Z, Kruk B. et al. Exercise hyperthermia as a factor limiting physical performance: Temperature effect on muscle metabolism. J Appl Physiol (1985) 1985; 59: 766-773
  • 48 Sawka MN, Young AJ, Cadarette BS. et al. Influence of heat stress and acclimation on maximal aerobic power. Eur J Appl Physiol Occup Physiol 1985; 53: 294-298
  • 49 Rowell LB, Brengelmann GL, Blackmon JR. et al. Splanchnic blood flow and metabolism in heat-stressed man. J Appl Physiol 1968; 24: 475-484
  • 50 Galbo H. The hormonal response to exercise. Diabetes Metab Rev 1986; 1: 385-408
  • 51 Febbraio MA, Snow RJ, Stathis CG. et al. Blunting the rise in body temperature reduces muscle glycogenolysis during exercise in humans. Exp Physiol 1996; 81: 685-693
  • 52 Gonzalez-Alonso J, Calbet JA, Nielsen B. Metabolic and thermodynamic responses to dehydration-induced reductions in muscle blood flow in exercising humans. J Physiol 1999; 520 Pt 2: 577-589
  • 53 Galbo H, Houston ME, Christensen NJ. et al. The effect of water temperature on the hormonal response to prolonged swimming. Acta Physiol Scand 1979; 105: 326-337
  • 54 Powers SK, Howley ET, Cox R. Blood lactate concentrations during submaximal work under differing environmental conditions. J Sports Med Phys Fitness 1985; 25: 84-89
  • 55 Richter EA, Ruderman NB, Gavras H. et al. Muscle glycogenolysis during exercise: dual control by epinephrine and contractions. Am J Physiol 1982; 242: E25-32
  • 56 Gonzalez-Alonso J, Mora-Rodriguez R, Below PR. et al. Dehydration markedly impairs cardiovascular function in hyperthermic endurance athletes during exercise. J Appl Physiol (1985) 1997; 82: 1229-1236
  • 57 Febbraio MA, Lambert DL, Starkie RL. et al. Effect of epinephrine on muscle glycogenolysis during exercise in trained men. J Appl Physiol (1985) 1998; 84: 465-470
  • 58 Wendling PS, Peters SJ, Heigenhauser GJ. et al. Epinephrine infusion does not enhance net muscle glycogenolysis during prolonged aerobic exercise. Can J Appl Physiol 1996; 21: 271-284
  • 59 Fink WJ, Costill DL, Van Handel PJ. Leg muscle metabolism during exercise in the heat and cold. Eur J Appl Physiol Occup Physiol 1975; 34: 183-190
  • 60 Howlett K, Febbraio M, Hargreaves M. Glucose production during strenuous exercise in humans: Role of epinephrine. Am J Physiol 1999; 276: E1130-1135
  • 61 Howlett K, Galbo H, Lorentsen J. et al. Effect of adrenaline on glucose kinetics during exercise in adrenalectomised humans. J Physiol 1999; 519 Pt 3: 911-921
  • 62 Jaworski K, Sarkadi-Nagy E, Duncan RE. et al. Regulation of triglyceride metabolism. IV. Hormonal regulation of lipolysis in adipose tissue. Am J Physiol Gastrointest Liver Physiol 2007; 293: G1-4
  • 63 Lafontan M, Langin D. Lipolysis and lipid mobilization in human adipose tissue. Prog Lipid Res 2009; 48: 275-297 DOI: 10.1016/j.plipres.2009.05.001.
  • 64 Martin WH. Effects of acute and chronic exercise on fat metabolism. Exerc Sport Sci Rev 1996; 24: 203-231
  • 65 Gollnick PD, Armstrong RB, Saubert CWt. et al. Glycogen depletion patterns in human skeletal muscle fibers during prolonged work. Pflugers Arch 1973; 344: 1-12
  • 66 Saltin B, Gagge AP, Stolwijk JA. Muscle temperature during submaximal exercise in man. J Appl Physiol 1968; 25: 679-688
  • 67 Saltin B, Hermansen L. Esophageal, rectal, and muscle temperature during exercise. J Appl Physiol 1966; 21: 1757-1762
  • 68 Reyes BA, Pendergast JS, Yamazaki S. Mammalian peripheral circadian oscillators are temperature compensated. J Biol Rhythms 2008; 23: 95-98
  • 69 Edwards RH, Harris RC, Hultman E. et al. Effect of temperature on muscle energy metabolism and endurance during successive isometric contractions, sustained to fatigue, of the quadriceps muscle in man. J Physiol 1972; 220: 335-352
  • 70 Uyeda K. Phosphofructokinase. Adv Enzymol Relat Areas Mol Biol 1979; 48: 193-244
  • 71 Ren JM, Hultman E. Regulation of phosphorylase a activity in human skeletal muscle. J Appl Physiol (1985) 1990; 69: 919-923
  • 72 Starkie RL, Hargreaves M, Lambert DL. et al. Effect of temperature on muscle metabolism during submaximal exercise in humans. Exp Physiol 1999; 84: 775-784
  • 73 Rowell LB, Blackmon JR, Martin RH. et al. Hepatic clearance of indocyanine green in man under thermal and exercise stresses. J Appl Physiol 1965; 20: 384-394
  • 74 Radigan LR, Robinson S. Effects of environmental heat stress and exercise on renal blood flow and filtration rate. J Appl Physiol 1949; 2: 185-191
  • 75 Bell AW, Hales JR, King RB. et al. Influence of heat stress on exercise-induced changes in regional blood flow in sheep. J Appl Physiol Respir Environ Exerc Physiol 1983; 55: 1916-1923
  • 76 Nielsen B, Hales JR, Strange S. et al. Human circulatory and thermoregulatory adaptations with heat acclimation and exercise in a hot, dry environment. J Physiol 1993; 460: 467-485
  • 77 Nielsen B, Strange S, Christensen NJ. et al. Acute and adaptive responses in humans to exercise in a warm, humid environment. Pflugers Arch 1997; 434: 49-56
  • 78 Savard GK, Nielsen B, Laszczynska J. et al. Muscle blood flow is not reduced in humans during moderate exercise and heat stress. J Appl Physiol (1985) 1988; 64: 649-657
  • 79 Smolander J, Louhevaara V. Effect of heat stress on muscle blood flow during dynamic handgrip exercise. Eur J Appl Physiol Occup Physiol 1992; 65: 215-220
  • 80 Pearson J, Low DA, Stohr E. et al. Hemodynamic responses to heat stress in the resting and exercising human leg: Insight into the effect of temperature on skeletal muscle blood flow. Am J Physiol Regul Integr Comp Physiol 2011; 300: R663-673
  • 81 Periard JD, Thompson MW, Caillaud C. et al. Influence of heat stress and exercise intensity on vastus lateralis muscle and prefrontal cortex oxygenation. Eur J Appl Physiol 2013; 113: 211-222
  • 82 Rupp T, Perrey S. Prefrontal cortex oxygenation and neuromuscular responses to exhaustive exercise. Eur J Appl Physiol 2008; 102: 153-163
  • 83 Clark MG, Colquhoun EQ, Rattigan S. et al. Vascular and endocrine control of muscle metabolism. Am J Physiol 1995; 268: E797-812
  • 84 Kim K, Monroe JC, Gavin TP. et al. Skeletal muscle adaptations to heat therapy. J Appl Physiol (1985) 2020; 128: 1635-1642
  • 85 Hyldahl RD, Peake JM. Combining cooling or heating applications with exercise training to enhance performance and muscle adaptations. J Appl Physiol (1985) 2020; 129: 353-365
  • 86 Freeman BC, Michels A, Song J. et al. Analysis of molecular chaperone activities using in vitro and in vivo approaches. Methods Mol Biol 2000; 99: 393-419
  • 87 Kuennen M, Gillum T, Dokladny K. et al. Thermotolerance and heat acclimation may share a common mechanism in humans. Am J Physiol Regul Integr Comp Physiol 2011; 301: R524-533
  • 88 Moseley PL. Heat shock proteins and heat adaptation of the whole organism. J Appl Physiol (1985) 1997; 83: 1413-1417 DOI: 10.1152/jappl.1997.83.5.1413.
  • 89 Horowitz M. Genomics and proteomics of heat acclimation. Front Biosci (Schol Ed) 2010; 2: 1068-1080
  • 90 Horowitz M. Heat acclimation, epigenetics, and cytoprotection memory. Compr Physiol 2014; 4: 199-230
  • 91 Tamura Y, Matsunaga Y, Masuda H. et al. Postexercise whole body heat stress additively enhances endurance training-induced mitochondrial adaptations in mouse skeletal muscle. Am J Physiol Regul Integr Comp Physiol 2014; 307: R931-943
  • 92 Skidmore R, Gutierrez JA, Guerriero V. et al. HSP70 induction during exercise and heat stress in rats: Role of internal temperature. Am J Physiol 1995; 268: R92-97
  • 93 Milne KJ, Noble EG. Exercise-induced elevation of HSP70 is intensity dependent. J Appl Physiol (1985) 2002; 93: 561-568
  • 94 Fehrenbach E, Niess AM, Voelker K. et al. Exercise intensity and duration affect blood soluble HSP72. Int J Sports Med 2005; 26: 552-557
  • 95 Morton JP, MacLaren DP, Cable NT. et al. Time course and differential responses of the major heat shock protein families in human skeletal muscle following acute nondamaging treadmill exercise. J Appl Physiol (1985) 2006; 101: 176-182
  • 96 Khassaf M, Child RB, McArdle A. et al. Time course of responses of human skeletal muscle to oxidative stress induced by nondamaging exercise. J Appl Physiol (1985) 2001; 90: 1031-1035
  • 97 McClung JP, Hasday JD, He JR. et al. Exercise-heat acclimation in humans alters baseline levels and ex vivo heat inducibility of HSP72 and HSP90 in peripheral blood mononuclear cells. Am J Physiol Regul Integr Comp Physiol 2008; 294: R185-191
  • 98 Gibson OR, Turner G, Tuttle JA. et al. Heat acclimation attenuates physiological strain and the HSP72, but not HSP90alpha, mRNA response to acute normobaric hypoxia. J Appl Physiol (1985) 2015; 119: 889-899
  • 99 Gibson OR, Mee JA, Taylor L. et al. Isothermic and fixed-intensity heat acclimation methods elicit equal increases in Hsp72 mRNA. Scand J Med Sci Sports 2015; 25: 259-268
  • 100 Drew BG, Ribas V, Le JA. et al. HSP72 is a mitochondrial stress sensor critical for Parkin action, oxidative metabolism, and insulin sensitivity in skeletal muscle. Diabetes 2014; 63: 1488-1505
  • 101 Liu CT, Brooks GA. Mild heat stress induces mitochondrial biogenesis in C2C12 myotubes. J Appl Physiol (1985) 2012; 112: 354-361
  • 102 Patton MG, Gillum TL, Szymanski MC. et al. Heat acclimation increases mitochondrial respiration capacity of C2C12 myotubes and protects against LPS-mediated energy deficit. Cell Stress Chaperones 2018; 23: 871-883
  • 103 Heesch MW, Shute RJ, Kreiling JL. et al. Transcriptional control, but not subcellular location, of PGC-1alpha is altered following exercise in a hot environment. J Appl Physiol (1985) 2016; 121: 741-749
  • 104 Slivka D, Shute R, Hailes W. et al. Exercise in the heat blunts improvements in aerobic power. Eur J Appl Physiol 2021; 121: 1715-1723
  • 105 Mang ZA, Fennel ZJ, Realzola RA. et al. Heat acclimation during low-intensity exercise increases VO2 max, Hsp72, but not markers of mitochondrial biogenesis and oxidative phosphorylation in skeletal tissue. Exp Physiol 2021; 106: 290-301
  • 106 Di Donato DM, West DW, Churchward-Venne TA. et al. Influence of aerobic exercise intensity on myofibrillar and mitochondrial protein synthesis in young men during early and late postexercise recovery. Am J Physiol Endocrinol Metab 2014; 306: E1025-1032
  • 107 McGlynn ML, Collins C, Hailes W. et al. Heat Acclimation in Females Does Not Limit Aerobic Exercise Training Outcomes. Int J Environ Res Public Health 2022; 19: 5554
  • 108 Gagnon D, Kenny GP. Sex differences in thermoeffector responses during exercise at fixed requirements for heat loss. J Appl Physiol (1985) 2012; 113: 746-757
  • 109 Gagnon D, Kenny GP. Sex modulates whole-body sudomotor thermosensitivity during exercise. J Physiol 2011; 589: 6205-6217
  • 110 Gute D, Fraga C, Laughlin MH. et al. Regional changes in capillary supply in skeletal muscle of high-intensity endurance-trained rats. J Appl Physiol (1985) 1996; 81: 619-626
  • 111 Ross M, Kargl CK, Ferguson R. et al. Exercise-induced skeletal muscle angiogenesis: Impact of age, sex, angiocrines and cellular mediators. Eur J Appl Physiol 2023; 123: 1415-1432
  • 112 Robbins JL, Duscha BD, Bensimhon DR. et al. A sex-specific relationship between capillary density and anaerobic threshold. J Appl Physiol (1985) 2009; 106: 1181-1186
  • 113 Mitchell EA, Martin NRW, Turner MC. et al. The combined effect of sprint interval training and postexercise blood flow restriction on critical power, capillary growth, and mitochondrial proteins in trained cyclists. J Appl Physiol (1985) 2019; 126: 51-59
  • 114 Green DJ, Hopman MT, Padilla J. et al. Vascular Adaptation to Exercise in Humans: Role of Hemodynamic Stimuli. Physiol Rev 2017; 97: 495-528
  • 115 Egginton S, Badr I, Williams J. et al. Physiological angiogenesis is a graded, not threshold, response. J Physiol 2011; 589: 195-206
  • 116 Kuhlenhoelter AM, Kim K, Neff D. et al. Heat therapy promotes the expression of angiogenic regulators in human skeletal muscle. Am J Physiol Regul Integr Comp Physiol 2016; 311: R377-391
  • 117 Chiesa ST, Trangmar SJ, Kalsi KK. et al. Local temperature-sensitive mechanisms are important mediators of limb tissue hyperemia in the heat-stressed human at rest and during small muscle mass exercise. Am J Physiol Heart Circ Physiol 2015; 309: H369-380
  • 118 Olfert IM, Howlett RA, Wagner PD. et al. Myocyte vascular endothelial growth factor is required for exercise-induced skeletal muscle angiogenesis. Am J Physiol Regul Integr Comp Physiol 2010; 299: R1059-1067
  • 119 Porporato PE, Payen VL, De Saedeleer CJ. et al. Lactate stimulates angiogenesis and accelerates the healing of superficial and ischemic wounds in mice. Angiogenesis 2012; 15: 581-592
  • 120 Morland C, Andersson KA, Haugen OP. et al. Exercise induces cerebral VEGF and angiogenesis via the lactate receptor HCAR1. Nat Commun 2017; 8: 15557
  • 121 Li M, Fuchs S, Bose T. et al. Mild heat stress enhances angiogenesis in a co-culture system consisting of primary human osteoblasts and outgrowth endothelial cells. Tissue Eng Part C Methods 2014; 20: 328-339
  • 122 Rattan SI, Sejersen H, Fernandes RA. et al. Stress-mediated hormetic modulation of aging, wound healing, and angiogenesis in human cells. Ann N Y Acad Sci 2007; 1119: 112-121
  • 123 Ives SJ, Andtbacka RH, Kwon SH. et al. Heat and alpha1-adrenergic responsiveness in human skeletal muscle feed arteries: The role of nitric oxide. J Appl Physiol (1985) 2012; 113: 1690-1698
  • 124 Harris MB, Blackstone MA, Ju H. et al. Heat-induced increases in endothelial NO synthase expression and activity and endothelial NO release. Am J Physiol Heart Circ Physiol 2003; 285: H333-340
  • 125 Ikeda Y, Biro S, Kamogawa Y. et al. Repeated thermal therapy upregulates arterial endothelial nitric oxide synthase expression in Syrian golden hamsters. Jpn Circ J 2001; 65: 434-438
  • 126 Sobajima M, Nozawa T, Shida T. et al. Repeated sauna therapy attenuates ventricular remodeling after myocardial infarction in rats by increasing coronary vascularity of noninfarcted myocardium. Am J Physiol Heart Circ Physiol 2011; 301: H548-554
  • 127 Miyauchi T, Miyata M, Ikeda Y. et al. Waon therapy upregulates Hsp90 and leads to angiogenesis through the Akt-endothelial nitric oxide synthase pathway in mouse hindlimb ischemia. Circ J 2012; 76: 1712-1721
  • 128 Huang PH, Chen JW, Lin CP. et al. Far infra-red therapy promotes ischemia-induced angiogenesis in diabetic mice and restores high glucose-suppressed endothelial progenitor cell functions. Cardiovasc Diabetol 2012; 11: 99
  • 129 Akasaki Y, Miyata M, Eto H. et al. Repeated thermal therapy up-regulates endothelial nitric oxide synthase and augments angiogenesis in a mouse model of hindlimb ischemia. Circ J 2006; 70: 463-470
  • 130 Kim K, Reid BA, Casey CA. et al. Effects of repeated local heat therapy on skeletal muscle structure and function in humans. J Appl Physiol (1985) 2020; 128: 483-492
  • 131 Hesketh K, Shepherd SO, Strauss JA. et al. Passive heat therapy in sedentary humans increases skeletal muscle capillarization and eNOS content but not mitochondrial density or GLUT4 content. Am J Physiol Heart Circ Physiol 2019; 317: H114-H123
  • 132 Kaluhiokalani J, Wallace T, Marchant E. et al. A comparison of passive heat treatment-induced vascular adaptations relative to exercise training. Physiology 2023; 38
  • 133 Sawka MN, Coyle EF. Influence of body water and blood volume on thermoregulation and exercise performance in the heat. Exerc Sport Sci Rev 1999; 27: 167-218
  • 134 Sawka MN, Leon LR, Montain SJ. et al. Integrated physiological mechanisms of exercise performance, adaptation, and maladaptation to heat stress. Compr Physiol 2011; 1: 1883-1928
  • 135 Bazett HCS FW, Doupe J, Scott JC. Climatic effects on the volume and composition of blood in man. Physiology 1940; 129: 69-83
  • 136 Montero D, Breenfeldt-Andersen A, Oberholzer L. et al. Erythropoiesis with endurance training: Dynamics and mechanisms. Am J Physiol Regul Integr Comp Physiol 2017; 312: R894-R902
  • 137 Mikkelsen CJ, Junge N, Piil JF. et al. Prolonged Heat Acclimation and Aerobic Performance in Endurance Trained Athletes. Front Physiol 2019; 10: 1372 DOI: 10.3389/fphys.2019.01372.
  • 138 Ronnestad BR, Hamarsland H, Hansen J. et al. Five weeks of heat training increases haemoglobin mass in elite cyclists. Exp Physiol 2021; 106: 316-327
  • 139 Ronnestad BR, Lid OM, Hansen J. et al. Heat suit training increases hemoglobin mass in elite cross-country skiers. Scand J Med Sci Sports 2022; 32: 1089-1098
  • 140 Patterson MJ, Stocks JM, Taylor NA. Sustained and generalized extracellular fluid expansion following heat acclimation. J Physiol 2004; 559: 327-334
  • 141 Keiser S, Fluck D, Huppin F. et al. Heat training increases exercise capacity in hot but not in temperate conditions: A mechanistic counter-balanced cross-over study. Am J Physiol Heart Circ Physiol 2015; 309: H750-761
  • 142 Rendell RA, Prout J, Costello JT. et al. Effects of 10 days of separate heat and hypoxic exposure on heat acclimation and temperate exercise performance. Am J Physiol Regul Integr Comp Physiol 2017; 313: R191-R201
  • 143 Cowley ES, Olenick AA, McNulty KL. et al. “Invisible Sportswomen”: The Sex Data Gap in Sport and Exercise. Women Sport Phys Act J 2021; 29: 146-151
  • 144 Tyler CJ, Reeve T, Hodges GJ. et al. The Effects of Heat Adaptation on Physiology, Perception and Exercise Performance in the Heat: A Meta-Analysis. Sports Med 2016; 46: 1699-1724
  • 145 Kelly MK, Bowe SJ, Jardine WT. et al. Heat Adaptation for Females: A Systematic Review and Meta-Analysis of Physiological Adaptations and Exercise Performance in the Heat. Sports Med 2023; 53: 1395-1421
  • 146 Morton JP, Holloway K, Woods P. et al. Exercise training-induced gender-specific heat shock protein adaptations in human skeletal muscle. Muscle Nerve 2009; 39: 230-233
  • 147 Shinohara T, Takahashi N, Ooie T. et al. Estrogen inhibits hyperthermia-induced expression of heat-shock protein 72 and cardioprotection against ischemia/reperfusion injury in female rat heart. J Mol Cell Cardiol 2004; 37: 1053-1061
  • 148 Bombardier E, Vigna C, Iqbal S. et al. Effects of ovarian sex hormones and downhill running on fiber-type-specific HSP70 expression in rat soleus. J Appl Physiol (1985) 2009; 106: 2009-2015
  • 149 Gillum T, Kuennen M, Gourley C. et al. Sex differences in heat shock protein 72 expression in peripheral blood mononuclear cells to acute exercise in the heat. Int J Endocrinol Metab 2013; 11: e8739
  • 150 Mee JA, Gibson OR, Tuttle JA. et al. Leukocyte Hsp72 mRNA transcription does not differ between males and females during heat acclimation. Temperature (Austin) 2016; 3: 549-556
  • 151 Carter S, Solomon TPJ. In vitro experimental models for examining the skeletal muscle cell biology of exercise: The possibilities, challenges and future developments. Pflugers Arch 2019; 471: 413-429
  • 152 Nikolic N, Aas V. Electrical Pulse Stimulation of Primary Human Skeletal Muscle Cells. Methods Mol Biol 2019; 1889: 17-24
  • 153 Nikolic N, Bakke SS, Kase ET. et al. Electrical pulse stimulation of cultured human skeletal muscle cells as an in vitro model of exercise. PLoS One 2012; 7: e33203
  • 154 Nikolic N, Gorgens SW, Thoresen GH. et al. Electrical pulse stimulation of cultured skeletal muscle cells as a model for in vitro exercise – possibilities and limitations. Acta Physiol (Oxf) 2017; 220: 310-331