Repeated ischaemic preconditioning: a novel therapeutic intervention and potential underlying mechanisms

What is the topic of this review? This review discusses the effects of repeated exposure of tissue to ischaemic preconditioning on cardiovascular function, the attendant adaptations and their potential clinical relevance. What advances does it highlight? We discuss the effects of episodic exposure to ischaemic preconditioning to prevent and/or attenuate ischaemic injury and summarize evidence pertaining to improvements in cardiovascular function and structure. Discussion is provided regarding the potential mechanisms that contribute to both local and systemic adaptation. Findings suggest that clinical benefits result from both the prevention of ischaemic events and the attenuation of their consequences.

[1]  K. Garratt,et al.  Remote Ischemic Conditioning , 2017, Journal of cardiovascular pharmacology and therapeutics.

[2]  N. Cable,et al.  Heart failure is associated with exaggerated endothelial ischaemia–reperfusion injury and attenuated effect of ischaemic preconditioning , 2016, European journal of preventive cardiology.

[3]  Victoria S. Sprung,et al.  Impact of eight weeks of repeated ischaemic preconditioning on brachial artery and cutaneous microcirculatory function in healthy males , 2015, European journal of preventive cardiology.

[4]  Ischemic Conditioning Is Safe and Effective for Octo- and Nonagenarians in Stroke Prevention and Treatment , 2015, Neurotherapeutics.

[5]  F. He,et al.  Long-term, regular remote ischemic preconditioning improves endothelial function in patients with coronary heart disease , 2015, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[6]  I. Harman-boehm,et al.  Intermittent cycles of remote ischemic preconditioning augment diabetic foot ulcer healing , 2015, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[7]  N. Cable,et al.  Interval exercise, but not endurance exercise, prevents endothelial ischemia-reperfusion injury in healthy subjects. , 2015, American journal of physiology. Heart and circulatory physiology.

[8]  G. Heusch Molecular basis of cardioprotection: signal transduction in ischemic pre-, post-, and remote conditioning. , 2015, Circulation research.

[9]  H. Iwao,et al.  Repeated remote ischemic conditioning attenuates left ventricular remodeling via exosome-mediated intercellular communication on chronic heart failure after myocardial infarction. , 2015, International journal of cardiology.

[10]  D. Hausenloy,et al.  The mitochondrial permeability transition pore and its role in myocardial ischemia reperfusion injury. , 2015, Journal of molecular and cellular cardiology.

[11]  H. Bøtker,et al.  Remote ischemic conditioning: from experimental observation to clinical application: report from the 8th Biennial Hatter Cardiovascular Institute Workshop , 2014, Basic Research in Cardiology.

[12]  Mahavir Singh,et al.  Endoplasmic reticulum stress-dependent activation of ATF3 mediates the late phase of ischemic preconditioning. , 2014, Journal of molecular and cellular cardiology.

[13]  P. Whittaker,et al.  From Ischemic Conditioning to ‘Hyperconditioning’: Clinical Phenomenon and Basic Science Opportunity , 2014, Dose-response : a publication of International Hormesis Society.

[14]  P. Ferdinandy,et al.  Interaction of Risk Factors, Comorbidities, and Comedications with Ischemia/Reperfusion Injury and Cardioprotection by Preconditioning, Postconditioning, and Remote Conditioning , 2014, Pharmacological Reviews.

[15]  M. Hayward,et al.  Effect of remote ischaemic preconditioning on clinical outcomes in patients undergoing cardiac bypass surgery: a randomised controlled clinical trial , 2014, Heart.

[16]  K. Shimada,et al.  Remote ischemic conditioning improves coronary microcirculation in healthy subjects and patients with heart failure , 2014, Drug design, development and therapy.

[17]  R. Gladstone,et al.  MicroRNA-144 is a circulating effector of remote ischemic preconditioning , 2014, Basic Research in Cardiology.

[18]  D. Thijssen,et al.  Seven-day remote ischemic preconditioning improves local and systemic endothelial function and microcirculation in healthy humans. , 2014, American journal of hypertension.

[19]  M. Totzeck,et al.  Circulating Nitrite Contributes to Cardioprotection by Remote Ischemic Preconditioning , 2014, Circulation research.

[20]  H. Bøtker,et al.  Improved long-term clinical outcomes in patients with ST-elevation myocardial infarction undergoing remote ischaemic conditioning as an adjunct to primary percutaneous coronary intervention. , 2014, European heart journal.

[21]  R. Draijer,et al.  Flow-mediated dilation and cardiovascular risk prediction: a systematic review with meta-analysis. , 2013, International journal of cardiology.

[22]  M. Neuhäuser,et al.  Cardioprotective and prognostic effects of remote ischaemic preconditioning in patients undergoing coronary artery bypass surgery: a single-centre randomised, double-blind, controlled trial , 2013, The Lancet.

[23]  J. Vicencio,et al.  Remote ischaemic preconditioning involves signalling through the SDF-1α/CXCR4 signalling axis , 2013, Basic Research in Cardiology.

[24]  G. Borm,et al.  Aging attenuates the protective effect of ischemic preconditioning against endothelial ischemia-reperfusion injury in humans. , 2013, American journal of physiology. Heart and circulatory physiology.

[25]  T. Gori,et al.  Daily Ischemic Preconditioning Provides Sustained Protection From Ischemia–Reperfusion Induced Endothelial Dysfunction: A Human Study , 2013, Journal of the American Heart Association.

[26]  G. Heusch Cardioprotection: chances and challenges of its translation to the clinic , 2013, The Lancet.

[27]  R. Bolli,et al.  Stromal Cell–Derived Factor-1 α Confers Protection Against Myocardial Ischemia/Reperfusion Injury: Role of the Cardiac Stromal Cell–Derived Factor-1 α –CXCR4 Axis , 2013 .

[28]  J. Zweier,et al.  Early ischaemic preconditioning requires Akt- and PKA-mediated activation of eNOS via serine1176 phosphorylation. , 2013, Cardiovascular research.

[29]  E. Lo,et al.  Upper limb ischemic preconditioning prevents recurrent stroke in intracranial arterial stenosis , 2012, Neurology.

[30]  F. Gaita,et al.  Remote ischaemic preconditioning in coronary artery bypass surgery: a meta-analysis , 2012, Heart.

[31]  P. Kranke,et al.  Remote Ischemic Conditioning to Protect against Ischemia-Reperfusion Injury: A Systematic Review and Meta-Analysis , 2012, PloS one.

[32]  C. Zuurbier,et al.  Deletion of the Innate Immune NLRP3 Receptor Abolishes Cardiac Ischemic Preconditioning and Is Associated with Decreased Il-6/STAT3 Signaling , 2012, PloS one.

[33]  L. Becker,et al.  Remote ischemic preconditioning confers late protection against myocardial ischemia–reperfusion injury in mice by upregulating interleukin-10 , 2012, Basic Research in Cardiology.

[34]  H. Bøtker,et al.  Exercise-induced cardioprotection is mediated by a bloodborne, transferable factor , 2012, Basic Research in Cardiology.

[35]  C. Reid,et al.  Usefulness of transient and persistent no reflow to predict adverse clinical outcomes following percutaneous coronary intervention. , 2012, American Journal of Cardiology.

[36]  Heng Zhao,et al.  The Chronic Protective Effects of Limb Remote Preconditioning and the Underlying Mechanisms Involved in Inflammatory Factors in Rat Stroke , 2012, PloS one.

[37]  M. Caria,et al.  Ischemic preconditioning of the muscle improves maximal exercise performance but not maximal oxygen uptake in humans. , 2011, Journal of applied physiology.

[38]  D. Thijssen,et al.  Effects of exercise on endothelium and endothelium/smooth muscle cross talk: role of exercise-induced hemodynamics. , 2011, Journal of applied physiology.

[39]  A. Redington,et al.  Repeated Remote Ischemic Postconditioning Protects Against Adverse Left Ventricular Remodeling and Improves Survival in a Rat Model of Myocardial Infarction , 2011, Circulation research.

[40]  Helen Jones,et al.  Flow-mediated dilation and cardiovascular event prediction: does nitric oxide matter? , 2011, Hypertension.

[41]  Hirofumi Tanaka,et al.  Endothelial ischemia‐reperfusion injury in humans: association with age and habitual exercise , 2011, American journal of physiology. Heart and circulatory physiology.

[42]  B. Gersh 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 , 2011 .

[43]  C. Terkelsen,et al.  Remote Ischemic Conditioning in Patients With Myocardial Infarction Treated With Primary Angioplasty: Impact on Left Ventricular Function Assessed by Comprehensive Echocardiography and Gated Single-Photon Emission CT , 2010, Circulation. Cardiovascular imaging.

[44]  S. Vatner,et al.  Molecular mechanisms mediating preconditioning following chronic ischemia differ from those in classical second window. , 2010, American journal of physiology. Heart and circulatory physiology.

[45]  D. Yellon,et al.  The neural and humoral pathways in remote limb ischemic preconditioning , 2010, Basic Research in Cardiology.

[46]  D. Thijssen,et al.  Obligatory role of hyperaemia and shear stress in microvascular adaptation to repeated heating in humans , 2010, The Journal of physiology.

[47]  P. Abete,et al.  Ischemic preconditioning in the aging heart: From bench to bedside , 2010, Ageing Research Reviews.

[48]  C. Terkelsen,et al.  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 , 2010, The Lancet.

[49]  D. Thijssen,et al.  Shear Stress Mediates Endothelial Adaptations to Exercise Training in Humans , 2010, Hypertension.

[50]  T. Münzel,et al.  Ischemic and non-ischemic preconditioning: Endothelium-focused translation into clinical practice. , 2010, Clinical hemorheology and microcirculation.

[51]  I. Konstantinov,et al.  Remote ischemic preconditioning decreases adhesion and selectively modifies functional responses of human neutrophils. , 2010, The Journal of surgical research.

[52]  Charalampos Kossyvakis,et al.  Cardioprotective role of remote ischemic periconditioning in primary percutaneous coronary intervention: enhancement by opioid action. , 2010, JACC. Cardiovascular interventions.

[53]  Daniel J. Green,et al.  Impact of inactivity and exercise on the vasculature in humans , 2009, European Journal of Applied Physiology.

[54]  M. Hopman,et al.  Ischemic preconditioning improves maximal performance in humans , 2009, European Journal of Applied Physiology.

[55]  G. Fan,et al.  Peripheral Nociception Associated With Surgical Incision Elicits Remote Nonischemic Cardioprotection Via Neurogenic Activation of Protein Kinase C Signaling , 2009, Circulation.

[56]  Elena Kuzmin,et al.  Transient limb ischaemia remotely preconditions through a humoral mechanism acting directly on the myocardium: evidence suggesting cross-species protection. , 2009, Clinical science.

[57]  G. Heusch,et al.  Loss of cardioprotection with ageing. , 2009, Cardiovascular research.

[58]  M. Matsuzaki,et al.  Ischemic pre-conditioning enhances the mobilization and recruitment of bone marrow stem cells to protect against ischemia/reperfusion injury in the late phase. , 2009, Journal of the American College of Cardiology.

[59]  S. Vatner,et al.  Repetitive Ischemia by Coronary Stenosis Induces a Novel Window of Ischemic Preconditioning , 2008, Circulation.

[60]  J. Zweier,et al.  Cardiac Myocyte–Specific Expression of Inducible Nitric Oxide Synthase Protects Against Ischemia/Reperfusion Injury by Preventing Mitochondrial Permeability Transition , 2008, Circulation.

[61]  J. Appl,et al.  Importance of hemodynamic forces as signals for exercise-induced changes in endothelial cell phenotype. , 2008, Journal of applied physiology.

[62]  S. Koch,et al.  Coronary effluent from a preconditioned heart activates the JAK-STAT pathway and induces cardioprotection in a donor heart. , 2008, American journal of physiology. Heart and circulatory physiology.

[63]  P. Ferdinandy,et al.  Interaction of Cardiovascular Risk Factors with Myocardial Ischemia/Reperfusion Injury, Preconditioning, and Postconditioning , 2007, Pharmacological Reviews.

[64]  K. Chayama,et al.  Repetition of Ischemic Preconditioning Augments Endothelium-Dependent Vasodilation in Humans: Role of Endothelium-Derived Nitric Oxide and Endothelial Progenitor Cells , 2007, Arteriosclerosis, thrombosis, and vascular biology.

[65]  R. Bolli,et al.  The late phase of preconditioning and its natural clinical application—gene therapy , 2007, Heart Failure Reviews.

[66]  I. Konstantinov,et al.  Intermittent peripheral tissue ischemia during coronary ischemia reduces myocardial infarction through a KATP-dependent mechanism: first demonstration of remote ischemic perconditioning. , 2007, American journal of physiology. Heart and circulatory physiology.

[67]  David Garcia-Dorado,et al.  Loss of ischemic preconditioning's cardioprotection in aged mouse hearts is associated with reduced gap junctional and mitochondrial levels of connexin 43. , 2007, American journal of physiology. Heart and circulatory physiology.

[68]  F. Ohsuzu,et al.  Close relationship between the vasodilator response to acetylcholine in the brachial and coronary artery in suspected coronary artery disease. , 2005, International journal of cardiology.

[69]  J. Deanfield,et al.  Remote ischemic preconditioning provides early and late protection against endothelial ischemia-reperfusion injury in humans: role of the autonomic nervous system. , 2005, Journal of the American College of Cardiology.

[70]  B. O’Rourke,et al.  Mitochondrial K(ATP) channels in cell survival and death. , 2005, Journal of molecular and cellular cardiology.

[71]  M. Laughlin,et al.  Nonuniform effects of endurance exercise training on vasodilation in rat skeletal muscle. , 2005, Journal of applied physiology.

[72]  A. Boulton,et al.  New and experimental approaches to treatment of diabetic foot ulcers: a comprehensive review of emerging treatment strategies , 2004, Diabetic medicine : a journal of the British Diabetic Association.

[73]  D. Green,et al.  Effect of exercise training on endothelium‐derived nitric oxide function in humans , 2004, The Journal of physiology.

[74]  J. Downey,et al.  Chelerythrine, a highly selective protein kinase C inhibitor, blocks the antiinfarct effect of ischemic preconditioning in rabbit hearts , 1994, Cardiovascular Drugs and Therapy.

[75]  J. Downey,et al.  Bradykinin induces mitochondrial ROS generation via NO, cGMP, PKG, and mitoKATP channel opening and leads to cardioprotection. , 2004, American journal of physiology. Heart and circulatory physiology.

[76]  I. Asiedu-Gyekye,et al.  The "no-reflow" phenomenon in cerebral circulation. , 2003, Medical science monitor : international medical journal of experimental and clinical research.

[77]  C. Harrington,et al.  For Personal Use. Only Reproduce with Permission from the Lancet , 2022 .

[78]  G. Schuler,et al.  Regular Physical Activity Improves Endothelial Function in Patients With Coronary Artery Disease by Increasing Phosphorylation of Endothelial Nitric Oxide Synthase , 2003, Circulation.

[79]  D. Liem,et al.  Transient limb ischemia induces remote ischemic preconditioning in vivo. , 2003, Circulation.

[80]  W. Bao,et al.  Evidence for an essential role of cyclooxygenase-2 as a mediator of the late phase of ischemic preconditioning in mice , 2000, Basic Research in Cardiology.

[81]  R. Bolli The Late Phase of Preconditioning , 2000, Circulation research.

[82]  E. Pehkonen,et al.  Beneficial effects of ischemic preconditioning on right ventricular function after coronary artery bypass grafting. , 2000, The Annals of thoracic surgery.

[83]  A M Zeiher,et al.  Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. , 2000, Circulation.

[84]  E. Dickson,et al.  Rabbit heart can be "preconditioned" via transfer of coronary effluent. , 1999, American journal of physiology. Heart and circulatory physiology.

[85]  Wen Chao Regional ischemic preconditioning protects remote virgin myocardium from subsequent sustained coronary occlusion in rabbits , 1999 .

[86]  F. Ohsuzu,et al.  Endothelium-dependent flow-mediated vasodilation in coronary and brachial arteries in suspected coronary artery disease. , 1998, The American journal of cardiology.

[87]  K. Sugimachi,et al.  Amelioration of liver injury by ischaemic preconditioning , 1998, The British journal of surgery.

[88]  P. Ping,et al.  The nitric oxide hypothesis of late preconditioning , 1998, Basic Research in Cardiology.

[89]  G. Heusch,et al.  Ischemic preconditioning in pigs: a graded phenomenon: its relation to adenosine and bradykinin. , 1998, Circulation.

[90]  R. Bolli,et al.  Nitric oxide synthase is the mediator of late preconditioning against myocardial infarction in conscious rabbits. , 1998, Circulation.

[91]  D. Yellon,et al.  Ischaemic preconditioning reduces troponin T release in patients undergoing coronary artery bypass surgery. , 1997, Heart.

[92]  D. Duncker,et al.  Myocardial protection by brief ischemia in noncardiac tissue. , 1996, Circulation.

[93]  M. Ashraf,et al.  Direct evidence that initial oxidative stress triggered by preconditioning contributes to second window of protection by endogenous antioxidant enzyme in myocytes. , 1996, Circulation.

[94]  C. Forrest,et al.  Acute ischaemic preconditioning protects against skeletal muscle infarction in the pig. , 1995, Cardiovascular research.

[95]  M. Hori,et al.  Effect of angina pectoris on myocardial protection in patients with reperfused anterior wall myocardial infarction: retrospective clinical evidence of "preconditioning". , 1995, Journal of the American College of Cardiology.

[96]  M. Galvani,et al.  Prodromal angina limits infarct size. A role for ischemic preconditioning. , 1995, Circulation.

[97]  C. Cannon,et al.  Previous angina alters in-hospital outcome in TIMI 4. A clinical correlate to preconditioning? , 1995, Circulation.

[98]  D. Latchman,et al.  Cardiac stress protein elevation 24 hours after brief ischemia or heat stress is associated with resistance to myocardial infarction. , 1993, Circulation.

[99]  R. Kloner,et al.  Regional Ischemic 'Preconditioning' Protects Remote Virgin Myocardium From Subsequent Sustained Coronary Occlusion , 1993, Circulation.

[100]  J. Downey,et al.  Protection Against Infarction Afforded by Preconditioning is Mediated by A1 Adenosine Receptors in Rabbit Heart , 1991, Circulation.

[101]  R. Jennings,et al.  Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. , 1986, Circulation.

[102]  M. Matsuzaki,et al.  Effects of the presence or absence of preceding angina pectoris on left ventricular function after acute myocardial infarction. , 1984, American heart journal.