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Current Status of Research on the Protective Effects of Remote Ischemic Preconditioning on the Myocardium

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DOI: 10.23977/cardvs.2022.020101 | Downloads: 20 | Views: 1176


Shu Song 1, Jiashuo Li 1, Yibo Wang 1, Tianxiang Chen 1, Lili Gu 1, Mengyuan Tao 1, Shuhui Sun 1, Jinkun Xi 1, Wenji Liang 1, Xiaohan Yu 1, Zhumei Sun 1


1 School of Clinical Medicine, North China University of Science and Technology, Tangshan, Hebei, 063000, China

Corresponding Author

Zhumei Sun


After the blocked blood vessel regains blood supply, a more severe injury than the original injury will occur, called ischemia-reperfusion injury (IRI), and the current classical method to mitigate IRI is remote ischemic preconditioning (RIPC) is when severe ischemia/hypoxia occurs in essential organs of the body (heart, brain, kidneys), Intermittent blocking and re-communication of distal limbs are regulated, thereby inducing the endogenous protective mechanism in the body and exerting the ischemic protection effect of essential organs. RIPC can trigger a range of mechanisms in the body to mitigate IRI, particularly protective impacts on the heart, but the specific mechanisms are unclear. RIPC has gradually moved from basic research to clinical trials with continuous exploration. The primary purpose of this paper is to summarize the research progress of the endogenous protection mechanism of RIPC in recent years, including the study of humoral mechanism and neural mechanism; as well as to organize the clinical applications related to RIPC in recent years, suggesting the potential value of RIPC and providing ideas for future research and application of RIPC.


Remote ischemic preconditioning, Myocardial reperfusion injury, Myocardial protection mechanism, Clinical application


Shu Song, Jiashuo Li, Yibo Wang, Tianxiang Chen, Lili Gu, Mengyuan Tao, Shuhui Sun, Jinkun Xi, Wenji Liang, Xiaohan Yu, Zhumei Sun, Current Status of Research on the Protective Effects of Remote Ischemic Preconditioning on the Myocardium. Cardiology and Vascular System (2022) Vol. 2: 1-10. DOI:


[1] China Cardiovascular Health and Disease Report 2020 Writing Group. Overview of the China Cardiovascular Health and Disease Report 2020. China Cardiovascular Disease Research 2021, Vol. 19, No. 7, July 2021.
[2] Funk F, Kronenbitter A, Isić M, et al. (2022) Diabetes disturbs functional adaptation of the remote myocardium after ischemia/reperfusion. J Mol Cell Cardiol. 
[3] Kerendi F, Kin H, Halkos M E, et al. (2005) Remote postconditioning. Brief renal ischemia and reperfusion applied before coronary artery reperfusion reduces myocardial infarct size via endogenous activation of adenosine receptors. Basic Res Cardiol, 100(5): 404-12.
[4] Choi EK, Jung H, Jeon S, et al. (2020) Role of Remote Ischemic Preconditioning in Hepatic Ischemic Reperfusion Injury. Dose Response. 18(3): 1559325820946923.
[5] Li DY, Liu WT, Wang GY, et al. (2018) Impact of combined ischemic preconditioning and remote ischemic perconditioning on ischemia-reperfusion injury after liver transplantation. Sci Rep. 8 (1):17979. 
[6] Whitaker J, Tschabrunn CM, Jang J, et al. (2018) Cardiac MR Characterization of left ventricular remodeling in a swine model of infarct followed by reperfusion. J Magn Reson Imaging. 
[7] Lieder HR, Skyschally A, Heusch G, et al. (2019) Plasma from remotely conditioned pigs reduces infarct size when given before or after ischemia to isolated perfused rat hearts. Pflugers Arch. 471 (11-12):1371-1379. 
[8] Kundumani-Sridharan V, Subramani J, Owens C, et al. (2021) Nrg1β Released in Remote Ischemic Preconditioning Improves Myocardial Perfusion and Decreases Ischemia/Reperfusion Injury via ErbB2-Mediated Rescue of Endothelial Nitric Oxide Synthase and Abrogation of Trx2 Autophagy. Arterioscler Thromb. Vasc Biol. 41 (8):2293-2314. 
[9] Heike A. Hildebrandt, Vincent K, et al. (2016) Kinetics and signal activation properties of circulating factor(s) from healthy volunteers undergoing remote ischemic pre ⁃ conditioning. J Am Coll Cardiol, 1(1⁃2):3⁃13.
[10] Böning A, Flicker L, Rodriguez-Montesinos J, et al. (2022) Remote ischemic preconditioning in patients undergoing cardiac surgery with six ischemic cycles. Perfusion. 2676591221115260. 
[11] Liu X, Huang Y, Pokreisz P, et al. Nitric oxide inhalation improves microvascular flow and decreases infarction size after myocardial ischemia and reperfusion. J Am Coll Cardiol, 2007, 50(8): 808-17.
[12] Jung H, Choi EK, Baek SI, et al. (2019) The Effect of Nitric Oxide on Remote Ischemic Preconditioning in Renal Ischemia Reperfusion Injury in Rats. Dose Response. 17 (2):1559325819853651. 
[13] Grau M, Kollikowski A, Bloch W. (2016) Remote ischemia preconditioning increases red blood cell deformability through red blood cell-nitric oxide synthase activation. clin Hemorheol Microcirc. 63 (3):185-97. 
[14] Parray A, Ma Y, Alam M, et al. (2020) An increase in AMPK/e-NOS signaling and attenuation of MMP-9 may contribute to remote ischemic perconditioning associated neuroprotection in rat model of focal ischemia. brain Res. 1740:146860. 
[15] Duan YF, An Y, Zhu F, et al. (2017) Remote ischemic preconditioning protects liver ischemia-reperfusion injury by regulating eNOS-NO pathway and liver microRNA expressions in fatty liver rats. Hepatobiliary Pancreat Dis Int. 16 (4):387-394.
[16] Nair A, Khan S, Omar S, et al. (2017) Remote ischaemic preconditioning suppresses endogenous plasma nitrite during ischaemia-reperfusion: a randomized controlled crossover pilot study. br J Clin Pharmacol. 83 (7):1416-1423. 
[17] Wadley GD, Lamon S, Alexander SE, et al. (2019) Noncoding RNAs regulating cardiac muscle mass. j Appl Physiol. 127(2):633-644. 
[18] MA W, ZHOU Y, LIU M, et al. (2021) Long non-coding RNA LINC00470 in serum derived exosome: a critical regulator for proliferation and autophagy in glioma cells. Cancer Cell Int. 21(1):149
[19] NASSER MI, MASOOD M, ADLAT S, et al. (2021) Mesenchymal stem cellderived exosome microRNA as therapy for cardiac ischemic injury. Biomed Pharmacother. 143:112118
[20] Li D, Zhao Y, Zhang C, et al. (2021) Plasma Exosomes at the Late Phase of Remote Ischemic Pre-conditioning Attenuate Myocardial Ischemia-Reperfusion Injury Through Transferring miR-126a-3p. front Cardiovasc Med. 8:736226. 
[21] Li CY, Ma W, Liu KP, et al. (2022) CircRNA and miRNA expression profiles during remote ischemic postconditioning attenuate brain ischemia/reperfusion injury. Brain Res Bull. 185:39-48. 
[22] Zatta A J, Kin H, Yoshishige D, et al. (2008) Evidence that cardioprotection by postconditioning involves preservation of myocardial opioid content and selective opioid receptor activation. American Journal of Physiology-Heart and Circulatory Physiology, 294(3): H1444-H51.
[23] Wang S Y, Cui X L, Xue F S, et al. (2016) Combined morphine and limb remote ischemic perconditioning provides an enhanced protection against myocardial ischemia/ reperfusion injury by antiapoptosis. J Surg Res, 202(1): 13-25.
[24] Aggarwal S, Virdi JK, Singh N, et al. (2019) Exploring the role and inter-relationship among nitric oxide, opioids, and K ATP channels in the signaling pathway underlying remote ischemic preconditioning induced cardioprotection in rats. Iran J Basic Med Sci. 22 (7):820-826. 
[25] Cheng X, Zhang YE, Lu X, et al. (2016) The involvement of central beta-endorphin in the cardioprotective effects of remote preconditioning mediated by the intracerebroventricular administration of morphine. Ir J Med Sci. 185 (2):423-31. 
[26] Contractor H, Lie RH, Cunnington C, et al. (2016) Adenosine Receptor Activation in the "Trigger" Limb of Remote Pre-Conditioning Mediates Human Endothelial Conditioning and Release of Circulating Cardioprotective Factor(s). JACC Basic Transl Sci. 1(6):461-471. 
[27] Leung CH, Wang L, Nielsen JM, et al. (2014) Remote cardioprotection by transfer of coronary effluent from ischemic preconditioned rabbit heart preserves mitochondrial integrity and function via adenosine receptor activation. Cardiovasc Drugs Ther. 28 (1):7-17. 
[28] Singh A, Randhawa PK, Bali A, et al. (2017) Exploring the Role of TRPV and CGRP in Adenosine Preconditioning and Remote Hind Limb Preconditioning-Induced Cardioprotection in Rats. Cardiovasc Drugs Ther. 31 (2):133-143. 
[29] Singh L, Kulshrestha R, Singh N, et al. (2018) Mechanisms involved in adenosine pharmacological preconditioning-induced cardioprotection. Korean J Physiol Pharmacol. 22 (3):225-234.
[30] Paez DT, Garces M, Calabró V, et al. (2019) Adenosine a 1 receptors and mitochondria: targets of remote ischemic preconditioning. Am J Physiol Heart Circ Physiol. 316 (3):H743-H750. 
[31] Jacob Raphael M D, Yaacov Gozal M D, Nachum Navot B S, et al. (2015) Activation of Adenosine Triphosphate-regulated Potassium Channels during Reperfusion Restores Isoflurane Postconditioning-induced Cardiac Protection in Acutely Hyperglycemic Rabbits. Anesthesiology, 1299-311.
[32] Gourine A, Gourine AV, Mastitskaya S, Ackland G. (2010) "Remote preconditioning reflex"-a neural pathway of cardioprotection during myocardial ischaemia and reperfusion induced by remote ischaemic preconditioning. Eur Hear J. 31(Suppl 1):319. 
[33] Kleinbongard P, Amanakis G, Skyschally A, et al. (2018) Reflection of Cardioprotection by Remote Ischemic Perconditioning in Attenuated ST-Segment Elevation During Ongoing Coronary Occlusion in Pigs: Evidence for Cardioprotection from Ischemic Injury. Circ Res. 122 (8):1102-1108. 
[34] Zhou D, Ding J, Ya J, et al. (2018) Remote ischemic conditioning: a promising therapeutic intervention for multi-organ protection. Aging (Albany NY). 10 (8):1825-1855. 
[35] Shingo Seki M, Masayuki Taniguchi M, Hiroshi Takeda M, et al. (2002) Inhibition by KB-R7943 of the Reverse Mode of the Na+/Ca2+ Exchanger Reduces Ca2+ Overload in Ischemic-Reperfused Rat Hearts. Circ J 66: 390-396, 2002
[36] Kiss A, Wu P, Schlederer M, et al. (2022) Sympathetic nerve innervation and metabolism in ischemic myocardium in response to remote ischemic perconditioning. Basic Res Cardiol. 117 (1):42. 
[37] Lambert E A, Thomas C J, Hemmes R, et al. (2016) Sympathetic nervous response to ischemia-reperfusion injury in humans is altered with remote ischemic preconditioning. Am J Physiol Heart Circ Physiol, 311(2): H364-70.
[38] GHo B C, SchoemakeR R G, Van Den Doel M A, et al. (1996) Myocardial protection by brief ischemia in noncardiac tissue. Circulation, 94(9): 2193-200.
[39] UITTErdijk A, Yetgin T, Te Lintel Hekkert M, et al. (2015) Vagal nerve stimulation started just prior to reperfusion limits infarct size and no-reflow. Basic Res Cardiol, 110(5): 508.
[40] Chen M, Li X, Yang H, et al. (2020) Hype or hope: Vagus nerve stimulation against acute myocardial ischemia-reperfusion injury. Trends Cardiovasc Med, 30(8): 481-8.
[41] Buchholz B, Kelly J, Muñoz M, et al. (2018) Vagal stimulation mimics preconditioning and postconditioning of ischemic myocardium in mice by activating different protection mechanisms. Am J Physiol Heart Circ Physiol. 314 (6):H1289-H1297.
[42] Pickard JM, Davidson SM, Hausenloy DJ, et al. (2016) Co-dependence of the neural and humoral pathways in the mechanism of remote ischemic conditioning. Basic Res Cardiol. 111(4):50. 
[43] Mastitskaya S, MARIna N, GourinE A, et al. (2012) Cardioprotection evoked by remote ischaemic preconditioning is critically dependent on the activity of vagal pre-ganglionic neurones. Cardiovasc Res, 95(4): 487-94.
[44] Verouhis D, Saleh N, Settergren M, et al. (2019) Remote ischemic conditioning protects against endothelial ischemia-reperfusion injury via a glucagon-like peptide-1 receptor-mediated mechanism in humans. Int J Cardiol. 274:40-44. 
[45] Redington K L, Disenhouse T, Strantzas S C, et al. (2012) Remote cardioprotection by direct peripheral nerve stimulation and topical capsaicin is mediated by circulating humoral factors. Basic Res Cardiol, 107(2): 241.
[46] Chen Wanlin, Zheng Guangsheng, Ping Yang, et al. (2017) Effect of remote ischemic preadaptation on arterial stiffness and heart rate variability in patients with angina pectoris. Journal of Clinical Cardiovascular Disease.
[47] Wang E-B. (2021) Effect of remote ischemic preadaptation on blood pressure and cytokines in patients with unstable angina. Xinxiang Medical College.
[48] He, Fengfeng. (2017) Myocardial protective effect of remote ischemic preadaptation in patients treated with coronary stenting. Electronic Journal of Modern Medicine and Health Research.
[49] Luo S J, Zhou Y J, Jia D A, et al. (2016) Myocardial protective effect of remote ischemic preadaptation in patients treated with stents for coronary artery disease. Chinese Journal of Evidence-Based Cardiovascular Medicine, Vol. 8, No. 7, July 2016.
[50] Hui Zhang, Sun Sujuan, Bi Yuanxiao, et al. (2022) Myocardial protective effect of remote ischemic preadaptation in patients undergoing percutaneous coronary intervention. Chinese Cardiovascular Disease Research January Vol. 20, No. 1, 2022,
[51] Prasad A, Gossl M, Hoyt J, et al. (2013) Remote ischemic preconditioning immediately before percutaneous coronary intervention does not impact myocardial necrosis, inflammatory response, and circulating endothelial progenitor cell counts: a single center randomized sham controlled trial. Catheter Cardiovasc Interv, 81 (6): 930-6.
[52] Tang R.X., Liu X.C., Liu M.Y., et al. (2020) Remote ischemic preadaptation combined with extracorporeal counterpulsation in patients with angina pectoris after PCI. Chinese Nursing Research.
[53] Leong R, Tang LQ, Chen YX, et al. (, 2017) Differential effects of early and late remote ischemic preadaptation in patients with unstable angina pectoris treated with percutaneous coronary intervention. Chinese Journal of Interventional Cardiology, Vol. 25, No. 10, October 2017.
[54] Chao Ma, Yuan Wenjin, Wu Hongyun, et al. (2018) Effects of different intensities of remote ischemic preadaptation on exercise tolerance, serum nitric oxide and endothelin in patients with stable angina. Journal of Jinggangshan University (Natural Science Edition).
[55] Gorjipour F, Saeedzadeh T, Toloueitabar Y, et al. (2022) Remote ischemic preconditioning effects on inflammatory markers and myocardial protection in coronary artery bypass graft surgery. Perfusion. 37 (1): 56-61. 
[56] Heusch G, Rassaf T. Time to Give Up on Cardioprotection? (2016) A Critical Appraisal of Clinical Studies on Ischemic Pre-, Post-, and Remote Conditioning. circ Res. 119 (5): 676-95. 
[57] Moscarelli M, Fiorentino F, Suleiman MS, et al. (2019) Remote ischaemic preconditioning in isolated aortic valve and coronary artery bypass surgery: a randomized trial†. Eur J Cardiothorac Surg. 55 (5): 905-912. 
[58] Tuter DS, Komarov RN, Glasachev OS, et al. (2019) Remote Ischemic Preconditioning with the Use of Lower Limb Before Coronary Artery Bypass Surgery with Cardiopulmonary Bypass and Anesthesia with Propofol. Kardiologiia. 59 (2): 38-44. 
[59] Cao B, Wang H, Zhang C, et al. (2018) Remote Ischemic Postconditioning (RIPC) of the Upper Arm Results in Protection from Cardiac Ischemia-Reperfusion Injury Following Primary Percutaneous Coronary Intervention (PCI) for Acute ST-Segment Elevation Myocardial Infarction (STEMI). Med Sci Monit. 24: 1017-1026. 
[60] Hausenloy DJ, Kharbanda RK, Møller UK, et al. (2019) Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial. Lancet. 394 (10207): 1415-1424.

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