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Aging and disease    2018, Vol. 9 Issue (1) : 165-171     DOI: 10.14336/AD.2017.1015
Perspectives |
Chronic Remote Ischemic Conditioning May Mimic Regular Exercise:Perspective from Clinical Studies
Zhao Wenbo1,2, Li Sijie2,3,4, Ren Changhong2,3, Meng Ran1, Ji Xunming2,4,*
¹Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
2Beijing Key Laboratory of Hypoxic Conditioning Translational Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China
3Beijing Municipal Geriatric Medical Research Center, Beijing, China
4National Clinical Research Center for Geriatric Disorders, Beijing, China
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Chronic remote ischemic conditioning (RIC), particularly long-term repeated RIC, has been applied in clinical trials with the expectation that it could play its protective roles for protracted periods. In sports medicine, chronic RIC has also been demonstrated to improve exercise performance, akin to improvements seen with regular exercise training. Therefore, chronic RIC may mimic regular exercise, and they may have similar underlying mechanisms. In this study, we explored the common underlying mechanisms of chronic RIC and physical exercise in protecting multiple organs and benefiting various populations, the advantages of chronic RIC, and the challenges for its popularization. Intriguingly, several underlying mechanisms of RIC and exercise have been shown to overlap. These include the production of many autacoids, enhanced ability for antioxidant activity, modulating immune and inflammatory responses. Therefore, it appears that chronic RIC, just like regular exercise, has beneficial effects in unhealthy, sub-healthy and healthy individuals. Compared with regular exercise, chronic RIC has several advantages, which may provide novel insights into the area of exercise and health. Chronic RIC may enrich the modes of exercise, and benefit individuals with severe diseases. Also, the disabled, and sub-healthy individuals are likely to benefit from chronic RIC either as an alternative to exercise or an adjunct to pharmacological or non-pharmacological therapy.

Keywords chronic remote ischemic conditioning      regular exercise      organ protection     
Corresponding Authors: Ji Xunming   
About author:

These authors have contributed equally to this work.

Issue Date: 01 February 2018
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Zhao Wenbo
Li Sijie
Ren Changhong
Meng Ran
Ji Xunming
Cite this article:   
Zhao Wenbo,Li Sijie,Ren Changhong, et al. Chronic Remote Ischemic Conditioning May Mimic Regular Exercise:Perspective from Clinical Studies[J]. Aging and disease, 2018, 9(1): 165-171.
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Different mechanismsCommon mechanisms
Increased cyclooxygenase-2
Elevated endoplasmic reticulum stress proteins
Increased HSP
Increased NO
Improve KATP function
Increased antioxidant capacity
Induced autophagy
Involvement of opioid system
Regulation of Immune/inflammatory
Regular exercise
Table 1  Comparison of mechanisms between RIC and exercise.
[1] Kodama S, Saito K, Tanaka S, Maki M, Yachi Y, Asumi M,et al. (2009). Cardiorespiratory fitness as a quantitative predictor of all-cause mortality and cardiovascular events in healthy men and women: a meta-analysis. JAMA, 301(19): 2024-2035.
[2] Kushi LH, Doyle C, McCullough M, Rock CL, Demark-Wahnefried W, Bandera EV,et al. (2012). American Cancer Society Guidelines on nutrition and physical activity for cancer prevention: reducing the risk of cancer with healthy food choices and physical activity. CA Cancer J Clin, 62(1): 30-67.
[3] Kyu HH, Bachman VF, Alexander LT, Mumford JE, Afshin A, Estep K,et al. (2016). Physical activity and risk of breast cancer, colon cancer, diabetes, ischemic heart disease, and ischemic stroke events: systematic review and dose-response meta-analysis for the Global Burden of Disease Study 2013. BMJ, 354: i3857.
[4] Michaud DS, Giovannucci E, Willett WC, Colditz GA, Stampfer MJ, Fuchs CS (2001). Physical activity, obesity, height, and the risk of pancreatic cancer. JAMA, 286(8): 921-929.
[5] Herring MP, O'Connor PJ, Dishman RK (2010). The effect of exercise training on anxiety symptoms among patients: a systematic review. Arch Intern Med, 170(4): 321-331.
[6] Lee IM, Djousse L, Sesso HD, Wang L, Buring JE (2010). Physical activity and weight gain prevention. JAMA, 303(12): 1173-1179.
[7] Harris MB, Starnes JW (2001). Effects of body temperature during exercise training on myocardial adaptations. Am J Physiol Heart Circ Physiol, 280(5): H2271-2280.
[8] Nicholson CK, Lambert JP, Chow CW, Lefer DJ, Calvert JW (2013). Chronic exercise downregulates myocardial myoglobin and attenuates nitrite reductase capacity during ischemia-reperfusion. J Mol Cell Cardiol, 64: 1-10.
[9] Lee Y, Min K, Talbert EE, Kavazis AN, Smuder AJ, Willis WT,et al. (2012). Exercise protects cardiac mitochondria against ischemia-reperfusion injury. Med Sci Sports Exerc, 44(3): 397-405.
[10] Quindry JC, Miller L, McGinnis G, Kliszczewicz B, Irwin JM, Landram M,et al. (2012). Ischemia reperfusion injury, KATP channels, and exercise-induced cardioprotection against apoptosis. J Appl Physiol (1985), 113(3): 498-506.
[11] Galvao TF, Matos KC, Brum PC, Negrao CE, Luz PL, Chagas AC (2011). Cardioprotection conferred by exercise training is blunted by blockade of the opioid system. Clinics (Sao Paulo), 66(1): 151-157.
[12] Lennon SL, Quindry J, Hamilton KL, French J, Staib J, Mehta JL,et al. (2004). Loss of exercise-induced cardioprotection after cessation of exercise. J Appl Physiol (1985), 96(4): 1299-1305.
[13] Falvey EC, Eustace J, Whelan B, Molloy MS, Cusack SP, Shanahan F,et al. (2009). Sport and recreation-related injuries and fracture occurrence among emergency department attendees: implications for exercise prescription and injury prevention. Emerg Med J, 26(8): 590-595.
[14] Dahabreh IJ, Paulus JK (2011). Association of episodic physical and sexual activity with triggering of acute cardiac events: systematic review and meta-analysis. JAMA, 305(12): 1225-1233.
[15] Periard JD, Caillaud C, Thompson MW (2011). Central and peripheral fatigue during passive and exercise-induced hyperthermia. Med Sci Sports Exerc, 43(9): 1657-1665.
[16] Thompson PD, Franklin BA, Balady GJ, Blair SN, Corrado D, Estes NA, 3rd,et al. (2007). Exercise and acute cardiovascular events placing the risks into perspective: a scientific statement from the American Heart Association Council on Nutrition, Physical Activity, and Metabolism and the Council on Clinical Cardiology. Circulation, 115(17): 2358-2368.
[17] Li G, Xie F, Yan S, Hu X, Jin B, Wang J,et al. (2013). Subhealth: definition, criteria for diagnosis and potential prevalence in the central region of China. BMC Public Health, 13: 446.
[18] Murry CE, Jennings RB, Reimer KA (1986). Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation, 74(5): 1124-1136.
[19] Abete P, Testa G, Cacciatore F, Della-Morte D, Galizia G, Langellotto A,et al. (2011). Ischemic preconditioning in the younger and aged heart. Aging Dis, 2(2): 138-148.
[20] Kaur Randhawa P, Bali A, Singh Jaggi A (2014). RIPC for multiorgan salvage in clinical settings: Evolution of concept, evidences and mechanisms. Eur J Pharmacol. 746(5) 317-332.
[21] Li S, Hafeez A, Noorulla F, Geng X, Shao G, Ren C,et al. (2017). Preconditioning in neuroprotection: From hypoxia to ischemia. Prog Neurobiol, 157: 79-91.
[22] Hausenloy DJ, Barrabes JA, Bøtker HE, Davidson SM, Di LF, Downey J,et al. (2016). Ischaemic conditioning and targeting reperfusion injury: a 30 year voyage of discovery. Basic Res Cardiol, 111(6): 70.
[23] Koch S, Katsnelson M, Dong C, Perez-Pinzon M (2011). Remote ischemic limb preconditioning after subarachnoid hemorrhage: a phase Ib study of safety and feasibility. Stroke, 42(5): 1387-1391.
[24] Li S, Ma C, Shao G, Esmail F, Hua Y, Jia L,et al. (2015). Safety and Feasibility of Remote Limb Ischemic Preconditioning in Patients With Unilateral Middle Cerebral Artery Stenosis and Healthy Volunteers. Cell transplant, 24(9): 1901-1911.
[25] Celso Constantino L, Tasca CI, Boeck CR (2014). The Role of NMDA Receptors in the Development of Brain Resistance through Pre- and Postconditioning. Aging Dis, 5(6): 430-441.
[26] Hausenloy DJ, Yellon DM (2016). Ischaemic conditioning and reperfusion injury. Nat Rev Cardiol, 13(4): 193-209.
[27] Kuzuya T, Hoshida S, Yamashita N, Fuji H, Oe H, Hori M,et al. (1993). Delayed effects of sublethal ischemia on the acquisition of tolerance to ischemia. Circ Res 72 (6): 1293-1299.
[28] Marber MS, Latchman DS, Walker JM, Yellon DM (1993). Cardiac stress protein elevation 24 hours after brief ischemia or heat stress is associated with resistance to myocardial infarction. Circulation, 88(3): 1264.
[29] Meng R, Asmaro K, Meng L, Liu Y, Ma C, Xi C,et al. (2012). Upper limb ischemic preconditioning prevents recurrent stroke in intracranial arterial stenosis. Neurology, 79(18): 1853-1861.
[30] Meng R, Ding Y, Asmaro K, Brogan D, Meng L, Sui M,et al. (2015). Ischemic Conditioning Is Safe and Effective for Octo- and Nonagenarians in Stroke Prevention and Treatment. Neurotherapeutics, 12(3): 667-677.
[31] Zhao W, Meng R, Ma C, Hou B, Jiao L, Zhu F,et al. (2017). Safety and Efficacy of Remote Ischemic Preconditioning in Patients With Severe Carotid Artery Stenosis Before Carotid Artery Stenting: A Proof-of-Concept, Randomized Controlled Trial. Circulation, 135(14): 1325-1335.
[32] Ren C, Gao X, Steinberg GK, Zhao H (2008). Limb remote-preconditioning protects against focal ischemia in rats and contradicts the dogma of therapeutic time windows for preconditioning. Neuroscience, 151(4): 1099-1103.
[33] Carroll CM, Carroll SMOvergoor ML, Tobin G, Barker JH (1997). Acute ischemic preconditioning of skeletal muscle prior to flap elevation augments muscle-flap survival. Plast Reconstr Surg, 100(1): 58-65.
[34] Pang CY, Yang RZ, Zhong A, Xu N, Boyd B, Forrest CR (1995). Acute ischaemic preconditioning protects against skeletal muscle infarction in the pig. Cardiovasc Res, 29(6): 782-788.
[35] Noakes TD (2000). Physiological models to understand exercise fatigue and the adaptations that predict or enhance athletic performance. Scand J Med Sci Sports, 10(3): 123-145.
[36] Jean-St-Michel E, Manlhiot C, Li J, Tropak M, Michelsen MM, Schmidt MR,et al. (2011). Remote preconditioning improves maximal performance in highly trained athletes. Med Sci Sports Exerc, 43(7): 1280-1286.
[37] Bailey TG, Jones H, Gregson W, Atkinson G, Cable NT, Thijssen DH (2012). Effect of ischemic preconditioning on lactate accumulation and running performance. Med Sci Sports Exerc, 44(11): 2084-2089.
[38] Costill DL, King DS, Thomas R and Hargreaves M (1985). Effects of Reduced Training on Muscular Power in Swimmers. Phys Sportsmed, 13(2): 94-101.
[39] Zarkadas PC, Carter JB, Banister EW (1995). Modelling the effect of taper on performance, maximal oxygen uptake, and the anaerobic threshold in endurance triathletes. Adv Exp Med Biol, 393: 179-186.
[40] Esposito F, Ronchi R, Milano G, Margonato V, Di Tullio S, Marini M,et al. (2011). Myocardial tolerance to ischemia-reperfusion injury, training intensity and cessation. Eur J Appl Physiol, 111(5): 859-868.
[41] Moran M, Blazquez I, Saborido A, Megias A (2005). Antioxidants and ecto-5'-nucleotidase are not involved in the training-induced cardioprotection against ischaemia-reperfusion injury. Exp Physiol, 90(4): 507-517.
[42] Hausenloy DJ, Yellon DM (2010). The second window of preconditioning (SWOP) where are we now? Cardiovasc Drugs Ther, 24(3): 235-254.
[43] Calvert JW, Lefer DJ (2013). Role of beta-adrenergic receptors and nitric oxide signaling in exercise-mediated cardioprotection. Physiology (Bethesda), 28(4): 216-224.
[44] Li X, Ren C, Li S, Han R, Gao J, Huang Q,et al. (2017). Limb Remote Ischemic Conditioning Promotes Myelination by Upregulating PTEN/Akt/mTOR Signaling Activities after Chronic Cerebral Hypoperfusion. Aging Dis, 8(4): 392-401.
[45] Hambrecht R, Adams V, Erbs S, Linke A, Krankel N, Shu Y,et al. (2003). Regular physical activity improves endothelial function in patients with coronary artery disease by increasing phosphorylation of endothelial nitric oxide synthase. Circulation, 107(25): 3152-3158.
[46] Liang Y, Li YP, He F, Liu XQ, Zhang JY (2015). Long-term, regular remote ischemic preconditioning improves endothelial function in patients with coronary heart disease. Braz J Med Biol Res, 48(6): 568-576.
[47] Brown DA, Chicco AJ, Jew KN, Johnson MS, Lynch JM, Watson PA,et al. (2006). 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): 913-924.
[48] Kraljevic J, Høydal MA, Ljubkovic M, Moreira JB, Jørgensen K, Ness HO,et al. (2015). Role of KATP Channels in Beneficial Effects of Exercise in Ischemic Heart Failure. Med Sci Sports Exerc, 47(12): 2504.
[49] Ong SB, Dongworth RK, Cabrera-Fuentes HA, Hausenloy DJ (2015). Role of the MPTP in conditioning the heart - translatability and mechanism. Br J Pharmacol, 172(8): 2074-2084.
[50] Sun J, Tong L, Luan Q, Deng J, Li Y, Li Z,et al. (2012). Protective effect of delayed remote limb ischemic postconditioning: role of mitochondrial KATP channels in a rat model of focal cerebral ischemic reperfusion injury. J Cereb Blood Flow Metab, 32(5): 851-859.
[51] Golbidi S, Laher I (2011). Molecular mechanisms in exercise-induced cardioprotection. Cardiol Res Pract, 2011: 972807.
[52] Frasier CR, Moukdar F, Patel HD, Sloan RC, Stewart LM, Alleman RJ,et al. (2013). Redox-dependent increases in glutathione reductase and exercise preconditioning: role of NADPH oxidase and mitochondria. Cardiovasc Res, 98(1): 47-55.
[53] Quindry JC, Hamilton KL (2013). Exercise and cardiac preconditioning against ischemia reperfusion injury. Curr Cardiol Rev, 9(3): 220-229.
[54] Dong HL, Zhang Y, Su BX, Zhu ZH, Gu QH, Sang HF,et al. (2010). Limb remote ischemic preconditioning protects the spinal cord from ischemia-reperfusion injury: a newly identified nonneuronal but reactive oxygen species-dependent pathway. Anesthesiology, 112(4): 881-891.
[55] Morihira M, Hasebe N, Baljinnyam E, Sumitomo K, Matsusaka T, Izawa K,et al. (2006). Ischemic preconditioning enhances scavenging activity of reactive oxygen species and diminishes transmural difference of infarct size. Am J Physiol Heart Circ Physiol, 290(2): H577-583.
[56] Park HK, Chu K, Jung KH, Lee ST, Bahn JJ, Kim M,et al. (2009). Autophagy is involved in the ischemic preconditioning. Neurosci Lett, 451(1): 16-19.
[57] Yan W, Dong H, Xiong L (2013). The protective roles of autophagy in ischemic preconditioning. Acta Pharmacol Sin, 34(5): 636-643.
[58] Martin-Rincon M, Morales-Alamo D, Calbet JAL (2017). Exercise-mediated modulation of autophagy in skeletal muscle. Scand J Med Sci Sports.
[59] Mooren FC, Kruger K (2015). Exercise, Autophagy, and Apoptosis. Prog Mol Biol Transl Sci, 135: 407-422.
[60] Halling JF, Pilegaard H (2017). Autophagy-Dependent Beneficial Effects of Exercise. Cold Spring Harb Perspect Med, 7(8): a029777.
[61] Schultz JE, Rose E, Yao Z, Gross GJ (1995). Evidence for involvement of opioid receptors in ischemic preconditioning in rat hearts. Am J Physiol , 268(5 Pt 2): H2157-2161.
[62] Idorn M, Hojman P (2016). Exercise-Dependent Regulation of NK Cells in Cancer Protection. Trends Mol Med, 22(7): 565-577.
[63] Pedersen B, Febbraio M (2012). Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat Rev Endocrinol, 8(8): 457-465.
[64] Lancaster GI, Febbraio MA (2014). The immunomodulating role of exercise in metabolic disease. Trends Immunol, 35(6): 262-269.
[65] Konstantinov IE, Arab S, Kharbanda RK, Li J, Cheung MM, Cherepanov V,et al. (2004). The remote ischemic preconditioning stimulus modifies inflammatory gene expression in humans. Physiol Genomics, 19(1): 143-150.
[66] Liu ZJ, Chen C, Li XR, Ran YY, Xu T, Zhang Y,et al. (2016). Remote Ischemic Preconditioning-Mediated Neuroprotection against Stroke is Associated with Significant Alterations in Peripheral Immune Responses. CNS Neurosci Ther, 22(1): 43-52.
[67] Botker HE, Kharbanda R, Schmidt MR, Bottcher M, Kaltoft AK, Terkelsen CJ,et al. (2010). Remote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: a randomised trial. Lancet, 375(9716): 727-734.
[68] Hougaard KD, Hjort N, Zeidler D, Sorensen L, Norgaard A, Hansen TM,et al. (2014). Remote ischemic perconditioning as an adjunct therapy to thrombolysis in patients with acute ischemic stroke: a randomized trial. Stroke, 45(1): 159-167.
[69] Krag AE, Kiil BJ, Hvas CL, Eschen GT, Hvas AM (2016). PO-62 - Remote ischemic preconditioning in head and neck cancer reconstruction - a randomized controlled trial. Thromb Res, 140 Suppl 1: S199.
[70] Le Page S, Prunier F (2015). Remote ischemic conditioning: Current clinical perspectives. J Cardiol, 66(2): 91-96.
[71] Madias JE (2015). Sustained blood pressure lowering effect of twice daily remote ischemic conditioning sessions in a normotensive/prehypertensive subject. Int J Cardiol, 182: 392-394.
[72] Madias JE, Koulouridis I (2014). Effect of repeat twice daily sessions of remote ischemic conditioning over the course of one week on blood pressure of a normotensive/prehypertensive subject. Int J Cardiol, 176(3): 1076-1077.
[73] Zhao W, Jiang F, Zhang Z, Zhang J, Ding Y, Ji X (2017). Remote Ischemic Conditioning: A Novel Non-Invasive Approach to Prevent Post-Stroke Depression. Front Aging Neurosci, 9 (270).
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