Cardiac Ischemia/Reperfusion Injury: The Beneficial Effects of Exercise

Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 999)


Cardiac ischemia reperfusion injury (IRI) occurs when the myocardium is revascularized after an episode of limited or absent blood supply. Many changes, including free radical production, calcium overload, protease activation, altered membrane lipids and leukocyte activation, contribute to IRI-induced myocardium damage. Aerobic exercise is the only countermeasure against IRI that can be sustained on a regular basis in clinical practice. Interestingly, both short-term (3–5 days) and long-term (several weeks) exercise increase myocardial tolerance, reduce infarct size area and arrhythmias induced by IRI. Exercise protects the heart against IRI in a biphasic manner. The early phase of cardioprotection occurs between 30 min and 3 h following an acute exercise bout, whilst the late phase is achieved within 24 h after the exercise bout and persists for several days. As for the exercise intensity, although controversial data exists, it is feasible that the amount of cardioprotection is proportional to exercise intensity and only achieved above a critical threshold. It is known that aerobic exercise produces a cardioprotective phenotype, however the mechanisms responsible for this phenomenon remain unclear. Apparently, aerobic exercise-induced preconditioning is dependent on several factors that work together to protect the heart. Altered nitric oxide (NO) signaling, increased levels of heat shock proteins (HSPs), enhanced function of ATP-sensitive potassium channels, increased activation of opioids system, and enhanced antioxidant capacity may contribute to exercise-induced cardioprotection. Much has been discovered from animal models involving exercise-induced cardioprotection against cardiac IRI, however translating these findings to clinical practice still represents the major challenge in this field.


Heart Ischemia/Reperfusion injury Signaling Myocardial 

Supplementary material

Video 10.1

(MP4 29483 kb)


  1. 1.
    Writing Group M, Mozaffarian D, Benjamin EJ et al (2016) Executive summary: heart disease and stroke statistics–2016 update: a report from the American Heart Association. Circulation 133(4):447–454CrossRefGoogle Scholar
  2. 2.
    Hausenloy DJ, Erik Botker H, Condorelli G et al (2013) Translating cardioprotection for patient benefit: position paper from the working Group of Cellular Biology of the heart of the European Society of Cardiology. Cardiovasc Res 98(1):7–27PubMedCrossRefGoogle Scholar
  3. 3.
    Kalogeris T, Baines CP, Krenz M et al (2012) Cell biology of ischemia/reperfusion injury. Int Rev Cell Mol Biol 298:229–317PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Hausenloy DJ, Yellon DM (2013) Myocardial ischemia-reperfusion injury: a neglected therapeutic target. J Clin Invest 123(1):92–100PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Brown DA, Jew KN, Sparagna GC et al (2003) Exercise training preserves coronary flow and reduces infarct size after ischemia-reperfusion in rat heart. J Appl Physiol (1985) 95(6):2510–2518CrossRefGoogle Scholar
  6. 6.
    Powers SK, Demirel HA, Vincent HK et al (1998) Exercise training improves myocardial tolerance to in vivo ischemia-reperfusion in the rat. Am J Phys 275(5 Pt 2):R1468–R1477Google Scholar
  7. 7.
    Demirel HA, Powers SK, Zergeroglu MA et al (2001) Short-term exercise improves myocardial tolerance to in vivo ischemia-reperfusion in the rat. J Appl Physiol (1985) 91(5):2205–2212Google Scholar
  8. 8.
    Taylor RP, Harris MB, Starnes JW (1999) Acute exercise can improve cardioprotection without increasing heat shock protein content. Am J Phys 276(3 Pt 2):H1098–H1102Google Scholar
  9. 9.
    Miller LE, Hosick PA, Wrieden J et al (2012) Evaluation of arrhythmia scoring systems and exercise-induced cardioprotection. Med Sci Sports Exerc 44(3):435–441PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Borges JP, Verdoorn KS, Daliry A et al (2014) Delta opioid receptors: the link between exercise and cardioprotection. PLoS One 9(11):e113541PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Dickson EW, Hogrefe CP, Ludwig PS et al (2008) Exercise enhances myocardial ischemic tolerance via an opioid receptor-dependent mechanism. Am J Physiol Heart Circ Physiol 294(1):H402–H408PubMedCrossRefGoogle Scholar
  12. 12.
    Yamashita N, Hoshida S, Otsu K et al (1999) Exercise provides direct biphasic cardioprotection via manganese superoxide dismutase activation. J Exp Med 189(11):1699–1706PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Laughlin MH, Bowles DK, Duncker DJ (2012) The coronary circulation in exercise training. Am J Physiol Heart Circ Physiol 302(1):H10–H23PubMedCrossRefGoogle Scholar
  14. 14.
    Laughlin MH (1985) McAllister RM (1992) exercise training-induced coronary vascular adaptation. J Appl Physiol 73(6):2209–2225Google Scholar
  15. 15.
    Hajnal A, Nagy O, Litvai A et al (2005) Nitric oxide involvement in the delayed antiarrhythmic effect of treadmill exercise in dogs. Life Sci 77(16):1960–1971PubMedCrossRefGoogle Scholar
  16. 16.
    Babai L, Szigeti Z, Parratt JR et al (2002) Delayed cardioprotective effects of exercise in dogs are aminoguanidine sensitive: possible involvement of nitric oxide. Clin Sci (Lond) 102(4):435–445CrossRefGoogle Scholar
  17. 17.
    Akita Y, Otani H, Matsuhisa S et al (2007) Exercise-induced activation of cardiac sympathetic nerve triggers cardioprotection via redox-sensitive activation of eNOS and upregulation of iNOS. Am J Physiol Heart Circ Physiol 292(5):H2051–H2059PubMedCrossRefGoogle Scholar
  18. 18.
    Nicholson CK, Lambert JP, Chow CW et al (2013) Chronic exercise downregulates myocardial myoglobin and attenuates nitrite reductase capacity during ischemia-reperfusion. J Mol Cell Cardiol 64(5):1–10PubMedCrossRefGoogle Scholar
  19. 19.
    Moran M, Blazquez I, Saborido A et al (2005) Antioxidants and ecto-5′-nucleotidase are not involved in the training-induced cardioprotection against ischaemia-reperfusion injury. Exp Physiol 90(4):507–517PubMedCrossRefGoogle Scholar
  20. 20.
    Lennon SL, Quindry J, Hamilton KL et al (2004) Loss of exercise-induced cardioprotection after cessation of exercise. J Appl Physiol (1985) 96(4):1299–1305CrossRefGoogle Scholar
  21. 21.
    Harris MB, Starnes JW (2001) Effects of body temperature during exercise training on myocardial adaptations. Am J Physiol Heart Circ Physiol 280(5):H2271–H2280PubMedGoogle Scholar
  22. 22.
    Marini M, Lapalombella R, Margonato V et al (2007) Mild exercise training, cardioprotection and stress genes profile. Eur J Appl Physiol 99(5):503–510PubMedCrossRefGoogle Scholar
  23. 23.
    Golbidi S, Laher I (2011) Molecular mechanisms in exercise-induced cardioprotection. Cardiol Res Pract 2011:972807PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Powers SK, Smuder AJ, Kavazis AN et al (2014) Mechanisms of exercise-induced cardioprotection. Physiology (Bethesda) 29(1):27–38Google Scholar
  25. 25.
    Brown DA, Chicco AJ, Jew KN et al (2005) Cardioprotection afforded by chronic exercise is mediated by the sarcolemmal, and not the mitochondrial, isoform of the KATP channel in the rat. J Physiol 569(Pt 3):913–924PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Zingman LV, Zhu Z, Sierra A et al (2011) Exercise-induced expression of cardiac ATP-sensitive potassium channels promotes action potential shortening and energy conservation. J Mol Cell Cardiol 51(1):72–81PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    French JP, Hamilton KL, Quindry JC et al (2008) Exercise-induced protection against myocardial apoptosis and necrosis: MnSOD, calcium-handling proteins, and calpain. FASEB J 22(8):2862–2871PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Hamilton KL, Staib JL, Phillips T et al (2003) Exercise, antioxidants, and HSP72: protection against myocardial ischemia/reperfusion. Free Radic Biol Med 34(7):800–809PubMedCrossRefGoogle Scholar
  29. 29.
    Powers SK, Murlasits Z, Wu M et al (2007) Ischemia-reperfusion-induced cardiac injury: a brief review. Med Sci Sports Exerc 39(9):1529–1536PubMedCrossRefGoogle Scholar
  30. 30.
    Solaini G, Harris DA (2005) Biochemical dysfunction in heart mitochondria exposed to ischaemia and reperfusion. Biochem J 390(Pt 2):377–394PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Rauch U, Schulze K, Witzenbichler B et al (1994) Alteration of the cytosolic-mitochondrial distribution of high-energy phosphates during global myocardial ischemia may contribute to early contractile failure. Circ Res 75(4):760–769PubMedCrossRefGoogle Scholar
  32. 32.
    Aldakkak M, Stowe DF, Chen Q et al (2008) Inhibited mitochondrial respiration by amobarbital during cardiac ischaemia improves redox state and reduces matrix Ca2+ overload and ROS release. Cardiovasc Res 77(2):406–415PubMedGoogle Scholar
  33. 33.
    Lesnefsky EJ, Chen Q, Tandler B et al (2017) Mitochondrial dysfunction and myocardial ischemia-reperfusion: implications for novel therapies. Annu Rev Pharmacol Toxicol 57:535–565PubMedCrossRefGoogle Scholar
  34. 34.
    Yellon DM, Hausenloy DJ (2007) Myocardial reperfusion injury. N Engl J Med 357(11):1121–1135PubMedCrossRefGoogle Scholar
  35. 35.
    Kim JS, Jin Y, Lemasters JJ (2006) Reactive oxygen species, but not Ca2+ overloading, trigger pH- and mitochondrial permeability transition-dependent death of adult rat myocytes after ischemia-reperfusion. Am J Physiol Heart Circ Physiol 290(5):H2024–H2034PubMedCrossRefGoogle Scholar
  36. 36.
    Honda HM, Korge P, Weiss JN (2005) Mitochondria and ischemia/reperfusion injury. Ann N Y Acad Sci 1047(1):248–258PubMedCrossRefGoogle Scholar
  37. 37.
    Vilahur G, Badimon L (2014) Ischemia/reperfusion activates myocardial innate immune response: the key role of the toll-like receptor. Front Physiol 5(5):496PubMedPubMedCentralGoogle Scholar
  38. 38.
    Kvietys PR, Granger DN (2012) Role of reactive oxygen and nitrogen species in the vascular responses to inflammation. Free Radic Biol Med 52(3):556–592PubMedCrossRefGoogle Scholar
  39. 39.
    Maes A, Van de Werf F, Nuyts J et al (1995) Impaired myocardial tissue perfusion early after successful thrombolysis. Impact on myocardial flow, metabolism, and function at late follow-up. Circulation 92(8):2072–2078PubMedCrossRefGoogle Scholar
  40. 40.
    Rezkalla SH, Kloner RA (2002) No-reflow phenomenon. Circulation 105(5):656–662PubMedCrossRefGoogle Scholar
  41. 41.
    Linkermann A, Green DR (2014) Necroptosis. N Engl J Med 370(5):455–465PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Nishida K, Yamaguchi O, Otsu K (2008) Crosstalk between autophagy and apoptosis in heart disease. Circ Res 103(4):343–351PubMedCrossRefGoogle Scholar
  43. 43.
    Xie M, Kong Y, Tan W et al (2014) Histone deacetylase inhibition blunts ischemia/reperfusion injury by inducing cardiomyocyte autophagy. Circulation 129(10):1139–1151PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Kostin S, Pool L, Elsasser A et al (2003) Myocytes die by multiple mechanisms in failing human hearts. Circ Res 92(7):715–724PubMedCrossRefGoogle Scholar
  45. 45.
    Zhao ZQ, Nakamura M, Wang NP et al (2000) Reperfusion induces myocardial apoptotic cell death. Cardiovasc Res 45(3):651–660PubMedCrossRefGoogle Scholar
  46. 46.
    Baines CP (2011) How and when do myocytes die during ischemia and reperfusion: the late phase. J Cardiovasc Pharmacol Ther 16(3–4):239–243PubMedCrossRefGoogle Scholar
  47. 47.
    Meissner A, Morgan JP (1995) Contractile dysfunction and abnormal Ca2+ modulation during postischemic reperfusion in rat heart. Am J Phys 268(1 Pt 2):H100–H111Google Scholar
  48. 48.
    Kohajda Z, Farkas-Morvay N, Jost N et al (2016) The effect of a novel highly selective inhibitor of the sodium/calcium exchanger (NCX) on cardiac arrhythmias in in vitro and in vivo experiments. PLoS One 11(11):e0166041PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Heyndrickx GR, Millard RW, McRitchie RJ et al (1975) Regional myocardial functional and electrophysiological alterations after brief coronary artery occlusion in conscious dogs. J Clin Invest 56(4):978–985PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Kloner RA, Jennings RB (2001) Consequences of brief ischemia: stunning, preconditioning, and their clinical implications: part 2. Circulation 104(25):3158–3167PubMedCrossRefGoogle Scholar
  51. 51.
    Bolli R, Marban E (1999) Molecular and cellular mechanisms of myocardial stunning. Physiol Rev 79(2):609–634PubMedGoogle Scholar
  52. 52.
    De Pauw M, Mubagwa K, Hodeige D et al (2015) Response to exercise and mechanical efficiency in non ischaemic stunning, induced by short term rapid pacing in dogs: a role for calcium ? Acta physiol(Oxf) 219(4):768–780CrossRefGoogle Scholar
  53. 53.
    Shah BN, Khattar RS, Senior R (2013) The hibernating myocardium: current concepts, diagnostic dilemmas, and clinical challenges in the post-STICH era. Eur Heart J 34(18):1323–1336PubMedCrossRefGoogle Scholar
  54. 54.
    Borges JP, Lessa MA (2015) Mechanisms involved in exercise-induced Cardioprotection: a systematic review. Arq Bras Cardiol 105(1):71–81PubMedPubMedCentralGoogle Scholar
  55. 55.
    Murry CE, Jennings RB, Reimer KA (1986) Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 74(5):1124–1136PubMedCrossRefGoogle Scholar
  56. 56.
    Riess ML, Stowe DF, Warltier DC (2004) Cardiac pharmacological preconditioning with volatile anesthetics: from bench to bedside? Am J Physiol Heart Circ Physiol 286(5):H1603–H1607PubMedCrossRefGoogle Scholar
  57. 57.
    Lambiase PD, Edwards RJ, Cusack MR et al (2003) Exercise-induced ischemia initiates the second window of protection in humans independent of collateral recruitment. J Am Coll Cardiol 41(7):1174–1182PubMedCrossRefGoogle Scholar
  58. 58.
    Galagudza M, Kurapeev D, Minasian S et al (2004) Ischemic postconditioning: brief ischemia during reperfusion converts persistent ventricular fibrillation into regular rhythm. Eur J Cardiothorac Surg 25(6):1006–1010PubMedCrossRefGoogle Scholar
  59. 59.
    Ferdinandy P, Schulz R, Baxter GF (2007) Interaction of cardiovascular risk factors with myocardial ischemia/reperfusion injury, preconditioning, and postconditioning. Pharmacol Rev 59(4):418–458PubMedCrossRefGoogle Scholar
  60. 60.
    Przyklenk K, Bauer B, Ovize M et al (1993) Regional ischemic ‘preconditioning’ protects remote virgin myocardium from subsequent sustained coronary occlusion. Circulation 87(3):893–899PubMedCrossRefGoogle Scholar
  61. 61.
    Hausenloy DJ, Yellon DM (2010) The second window of preconditioning (SWOP) where are we now? Cardiovasc Drugs Ther 24(3):235–254PubMedCrossRefGoogle Scholar
  62. 62.
    Kavazis AN (2009) Exercise preconditioning of the myocardium. Sports Med 39(11):923–935PubMedCrossRefGoogle Scholar
  63. 63.
    Sommerschild HT, Kirkeboen KA (2002) Preconditioning - endogenous defence mechanisms of the heart. Acta Anaesthesiol Scand 46(2):123–137PubMedCrossRefGoogle Scholar
  64. 64.
    Miller LE (2012) Endogenous opioids and exercise induced Cardioprotection. Auburn University, Alabama, Doctoral DissertationGoogle Scholar
  65. 65.
    Frasier CR, Moukdar F, Patel HD et al (2013) Redox-dependent increases in glutathione reductase and exercise preconditioning: role of NADPH oxidase and mitochondria. Cardiovasc Res 98(1):47–55PubMedCrossRefGoogle Scholar
  66. 66.
    Hamilton KL, Quindry JC, French JP et al (2004) MnSOD antisense treatment and exercise-induced protection against arrhythmias. Free Radic Biol Med 37(9):1360–1368PubMedCrossRefGoogle Scholar
  67. 67.
    Libonati JR, Gaughan JP, Hefner CA et al (1997) Reduced ischemia and reperfusion injury following exercise training. Med Sci Sports Exerc 29(4):509–516PubMedCrossRefGoogle Scholar
  68. 68.
    Demirel HA, Powers SK, Caillaud C et al (1998) Exercise training reduces myocardial lipid peroxidation following short-term ischemia-reperfusion. Med Sci Sports Exerc 30(8):1211–1216PubMedCrossRefGoogle Scholar
  69. 69.
    French JP, Quindry JC, Falk DJ et al (2006) Ischemia-reperfusion-induced calpain activation and SERCA2a degradation are attenuated by exercise training and calpain inhibition. Am J Physiol Heart Circ Physiol 290(1):H128–H136PubMedCrossRefGoogle Scholar
  70. 70.
    Quindry JC, Hamilton KL, French JP et al (2007) Exercise-induced HSP-72 elevation and cardioprotection against infarct and apoptosis. J Appl Physiol (1985) 103(3):1056–1062CrossRefGoogle Scholar
  71. 71.
    Powers SK, Lennon SL, Quindry J et al (2002) Exercise and cardioprotection. Curr Opin Cardiol 17(5):495–502PubMedCrossRefGoogle Scholar
  72. 72.
    Powers SK, Quindry JC, Kavazis AN (2008) Exercise-induced cardioprotection against myocardial ischemia-reperfusion injury. Free Radic Biol Med 44(2):193–201PubMedCrossRefGoogle Scholar
  73. 73.
    Berlin JA, Colditz GA (1990) A meta-analysis of physical activity in the prevention of coronary heart disease. Am J Epidemiol 132(4):612–628PubMedCrossRefGoogle Scholar
  74. 74.
    Sattelmair J, Pertman J, Ding EL et al (2011) Dose response between physical activity and risk of coronary heart disease: a meta-analysis. Circulation 124(7):789–795PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Paffenbarger RS Jr, Hyde RT, Wing AL et al (1986) Physical activity, all-cause mortality, and longevity of college alumni. N Engl J Med 314(10):605–613PubMedCrossRefGoogle Scholar
  76. 76.
    McElroy CL, Gissen SA, Fishbein MC (1978) Exercise-induced reduction in myocardial infarct size after coronary artery occlusion in the rat. Circulation 57(5):958–962PubMedCrossRefGoogle Scholar
  77. 77.
    Miller LE, McGinnis GR, Peters BA et al (2015) Involvement of the delta-opioid receptor in exercise-induced cardioprotection. Exp Physiol 100(4):410–421PubMedCrossRefGoogle Scholar
  78. 78.
    Libonati JR, Kendrick ZV (1985) Houser SR (2005) Sprint training improves postischemic, left ventricular diastolic performance. J Appl Physiol 99(6):2121–2127CrossRefGoogle Scholar
  79. 79.
    Frasier CR, Moore RL (1985) Brown DA (2011) exercise-induced cardiac preconditioning: how exercise protects your achy-breaky heart. J Appl Physiol 111(3):905–915CrossRefGoogle Scholar
  80. 80.
    Galvao TF, Matos KC, Brum PC et al (2011) Cardioprotection conferred by exercise training is blunted by blockade of the opioid system. Clinics (Sao Paulo) 66(1):151–157CrossRefGoogle Scholar
  81. 81.
    Starnes JW, Taylor RP, Ciccolo JT (2005) Habitual low-intensity exercise does not protect against myocardial dysfunction after ischemia in rats. Eur J Cardiovasc Prev Rehabil 12(2):169–174PubMedCrossRefGoogle Scholar
  82. 82.
    Locke M, Tanguay RM, Klabunde RE et al (1995) Enhanced postischemic myocardial recovery following exercise induction of HSP 72. Am J Phys 269(1 Pt 2):H320–H325Google Scholar
  83. 83.
    Lee Y, Min K, Talbert EE et al (2012) Exercise protects cardiac mitochondria against ischemia-reperfusion injury. Med Sci Sports Exerc 44(3):397–405PubMedCrossRefGoogle Scholar
  84. 84.
    Masson GS, Borges JP, da Silva PP et al (2016) Effect of continuous and interval aerobic exercise training on baroreflex sensitivity in heart failure. Auton Neurosci 197:9–13PubMedCrossRefGoogle Scholar
  85. 85.
    Bowles DK, Farrar RP, Starnes JW (1992) Exercise training improves cardiac function after ischemia in the isolated, working rat heart. Am J Phys 263(3 Pt 2):H804–H809Google Scholar
  86. 86.
    Esposito F, Ronchi R, Milano G et al (2011) Myocardial tolerance to ischemia-reperfusion injury, training intensity and cessation. Eur J Appl Physiol 111(5):859–868PubMedCrossRefGoogle Scholar
  87. 87.
    Lennon SL, Quindry JC, French JP et al (2004) Exercise and myocardial tolerance to ischaemia-reperfusion. Acta Physiol Scand 182(2):161–169PubMedCrossRefGoogle Scholar
  88. 88.
    Tjonna AE, Lee SJ, Rognmo O et al (2008) Aerobic interval training versus continuous moderate exercise as a treatment for the metabolic syndrome: a pilot study. Circulation 118(4):346–354PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Daussin FN, Zoll J, Dufour SP et al (2008) Effect of interval versus continuous training on cardiorespiratory and mitochondrial functions: relationship to aerobic performance improvements in sedentary subjects. Am J Physiol Regul Integr Comp Physiol 295(1):R264–R272PubMedCrossRefGoogle Scholar
  90. 90.
    Paes LS, Borges JP, Cunha FA et al (2016) Oxygen uptake, respiratory exchange ratio, or total distance: a comparison of methods to equalize exercise volume in Wistar rats. Braz J Med Biol Res 49(8)Google Scholar
  91. 91.
    Doustar Y, Soufi FG, Jafary A et al (2012) Role of four-week resistance exercise in preserving the heart against ischaemia-reperfusion-induced injury. Cardiovasc J Afr 23(8):451–455PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Spence AL, Naylor LH, Carter HH et al (2011) A prospective randomised longitudinal MRI study of left ventricular adaptation to endurance and resistance exercise training in humans. J Physiol 589(Pt 22):5443–5452PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Venckunas T, Simonavicius J, Marcinkeviciene JE (2016) Cardiac size of high-volume resistance trained female athletes: shaping the body but not the heart. Acta Physiol Hung 103(1):105–111CrossRefGoogle Scholar
  94. 94.
    Hambrecht R, Gielen S, Linke A et al (2000) Effects of exercise training on left ventricular function and peripheral resistance in patients with chronic heart failure: a randomized trial. JAMA 283(23):3095–3101PubMedCrossRefGoogle Scholar
  95. 95.
    Soufi FG, Saber MM, Ghiassie R et al (2011) Role of 12-week resistance training in preserving the heart against ischemia-reperfusion-induced injury. Cardiol J 18(2):140–145PubMedGoogle Scholar
  96. 96.
    Powers SK, Locke DHA (2001) Exercise, heat shock proteins, and myocardial protection from I-R injury. Med Sci Sports Exerc 33(3):386–392PubMedCrossRefGoogle Scholar
  97. 97.
    Locke M, Noble EG, Tanguay RM et al (1995) Activation of heat-shock transcription factor in rat heart after heat shock and exercise. Am J Phys 268(6 Pt 1):C1387–C1394Google Scholar
  98. 98.
    Yuan Y, Pan SS, Shen YJ (2016) Cardioprotection of exercise preconditioning involving heat shock protein 70 and concurrent autophagy: a potential chaperone-assisted selective macroautophagy effect. J Physiol Sci:1–13Google Scholar
  99. 99.
    Hamilton KL, Powers SK, Sugiura T et al (2001) Short-term exercise training can improve myocardial tolerance to I/R without elevation in heat shock proteins. Am J Physiol Heart Circ Physiol 281(3):H1346–H1352PubMedGoogle Scholar
  100. 100.
    Calvert JW, Lefer DJ (2013) Role of beta-adrenergic receptors and nitric oxide signaling in exercise-mediated cardioprotection. Physiology (Bethesda) 28(4):216–224Google Scholar
  101. 101.
    Calvert JW, Condit ME, Aragon JP et al (2011) Exercise protects against myocardial ischemia-reperfusion injury via stimulation of beta(3)-adrenergic receptors and increased nitric oxide signaling: role of nitrite and nitrosothiols. Circ Res 108(12):1448–1458PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Davis ME, Grumbach IM, Fukai T et al (2004) Shear stress regulates endothelial nitric-oxide synthase promoter activity through nuclear factor kappaB binding. J Biol Chem 279(1):163–168PubMedCrossRefGoogle Scholar
  103. 103.
    Farah C, Kleindienst A, Bolea G et al (2013) Exercise-induced cardioprotection: a role for eNOS uncoupling and NO metabolites. Basic Res Cardiol 108(6):389PubMedCrossRefGoogle Scholar
  104. 104.
    Taylor RP, Olsen ME, Starnes JW (2007) Improved postischemic function following acute exercise is not mediated by nitric oxide synthase in the rat heart. Am J Physiol Heart Circ Physiol 292(1):H601–H607PubMedCrossRefGoogle Scholar
  105. 105.
    Go YM, Park H, Koval M et al (2010) A key role for mitochondria in endothelial signaling by plasma cysteine/cystine redox potential. Free Radic Biol Med 48(2):275–283PubMedCrossRefGoogle Scholar
  106. 106.
    Lima B, Forrester MT, Hess DT et al (2010) S-nitrosylation in cardiovascular signaling. Circ Res 106(4):633–646PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Lawler JM, Rodriguez DA, Hord JM (2016) Mitochondria in the middle: exercise preconditioning protection of striated muscle. J Physiol 594(18):5161–5183PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Kavazis AN, McClung JM, Hood DA et al (2008) Exercise induces a cardiac mitochondrial phenotype that resists apoptotic stimuli. Am J Physiol Heart Circ Physiol 294(2):H928–H935PubMedCrossRefGoogle Scholar
  109. 109.
    Noma A (1983) ATP-regulated K+ channels in cardiac muscle. Nature 305(5930):147–148PubMedCrossRefGoogle Scholar
  110. 110.
    Li Y, Cai M, Cao L et al (2014) Endurance exercise accelerates myocardial tissue oxygenation recovery and reduces ischemia reperfusion injury in mice. PLoS One 9(12):e114205PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    Peng FL, Guo YJ, Mo WB et al (2014) Cardioprotective effects mitochondrial ATP-sensitive potassium channel in exercise conditioning. Genet Mol Res 13(3):7503–7512PubMedCrossRefGoogle Scholar
  112. 112.
    Quindry JC, Miller L, McGinnis G et al (2012) Ischemia reperfusion injury, KATP channels, and exercise-induced cardioprotection against apoptosis. J Appl Physiol (1985) 113(3):498–506CrossRefGoogle Scholar
  113. 113.
    Domenech R, Macho P, Schwarze H et al (2002) Exercise induces early and late myocardial preconditioning in dogs. Cardiovasc Res 55(3):561–566PubMedCrossRefGoogle Scholar
  114. 114.
    Quindry JC, Schreiber L, Hosick P et al (2010) Mitochondrial KATP channel inhibition blunts arrhythmia protection in ischemic exercised hearts. Am J Physiol Heart Circ Physiol 299(1):H175–H183PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Chicco AJ, Johnson MS, Armstrong CJ et al (2007) Sex-specific and exercise-acquired cardioprotection is abolished by sarcolemmal KATP channel blockade in the rat heart. Am J Physiol Heart Circ Physiol 292(5):H2432–H2437PubMedCrossRefGoogle Scholar
  116. 116.
    Schultz JE, Gross GJ (2001) Opioids and cardioprotection. Pharmacol Ther 89(2):123–137PubMedCrossRefGoogle Scholar
  117. 117.
    Aziz Q, Thomas AM, Khambra T et al (2012) Regulation of the ATP-sensitive potassium channel subunit, Kir6.2, by a Ca2+−dependent protein kinase C. J Biol Chem 287(9):6196–6207PubMedCrossRefGoogle Scholar
  118. 118.
    Akil H, Watson SJ, Young E et al (1984) Endogenous opioids: biology and function. Annu Rev Neurosci 7:223–255PubMedCrossRefGoogle Scholar
  119. 119.
    Oldroyd KG, Harvey K, Gray CE et al (1992) Beta endorphin release in patients after spontaneous and provoked acute myocardial ischaemia. Br Heart J 67(3):230–235PubMedPubMedCentralCrossRefGoogle Scholar
  120. 120.
    Falcone C, Guasti L, Ochan M et al (1993) Beta-endorphins during coronary angioplasty in patients with silent or symptomatic myocardial ischemia. J Am Coll Cardiol 22(6):1614–1620PubMedCrossRefGoogle Scholar
  121. 121.
    Thoren P, Floras JS, Hoffmann P et al (1990) Endorphins and exercise: physiological mechanisms and clinical implications. Med Sci Sports Exerc 22(4):417–428PubMedGoogle Scholar
  122. 122.
    Howlett TA, Tomlin S, Ngahfoong L et al (1984) Release of beta endorphin and met-enkephalin during exercise in normal women: response to training. Br Med J (Clin Res Ed) 288(6435):1950–1952CrossRefGoogle Scholar
  123. 123.
    Ferdinandy P, Hausenloy DJ, Heusch G et al (2014) Interaction of risk factors, comorbidities, and comedications with ischemia/reperfusion injury and cardioprotection by preconditioning, postconditioning, and remote conditioning. Pharmacol Rev 66(4):1142–1174PubMedCrossRefGoogle Scholar
  124. 124.
    Szilvassy Z, Ferdinandy P, Szilvassy J et al (1995) The loss of pacing-induced preconditioning in atherosclerotic rabbits: role of hypercholesterolaemia. J Mol Cell Cardiol 27(12):2559–2569PubMedCrossRefGoogle Scholar
  125. 125.
    McDonald MW, Hall KE, Jiang M et al (2014) Ischemia-reperfusion injury and hypoglycemia risk in insulin-treated T1DM rats following different modalities of regular exercise. Physiol Rep 2(11)Google Scholar
  126. 126.
    Zdrenghea D, Ilea M, Predescu D et al (1998) Ischemic preconditioning during successive exercise testing. Rom J Intern Med 36(3–4):161–165PubMedGoogle Scholar
  127. 127.
    Lalonde F, Poirier P, Arvisais D et al (2015) Exercise-induced ischemic preconditioning and the potential application to cardiac rehabilitation. J Cardiopulm Rehabil Prev 35:93–102PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2017

Authors and Affiliations

  1. 1.Institute of Physical Education and SportsState University of Rio de JaneiroRio de JaneiroBrazil
  2. 2.Federal University of Rio de JaneiroMacaéBrazil

Personalised recommendations