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  • Review Article
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The therapeutic potential of ischemic conditioning: an update

Nature Reviews Cardiology volume 8, pages 619–629 (2011)Cite this article

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Abstract

Novel approaches are required to improve clinical outcomes in patients with coronary heart disease (CHD). Ischemic conditioning—the practice of applying brief episodes of nonlethal ischemia and reperfusion to confer protection against a sustained episode of lethal ischemia and reperfusion injury—is one potential therapeutic strategy. Importantly, the protective stimulus can be applied before (ischemic preconditioning) or after (ischemic perconditioning) onset of the sustained episode of lethal ischemia, or even at the onset of myocardial reperfusion (ischemic postconditioning). Furthermore, the protective stimulus can be applied noninvasively by placing a blood-pressure cuff on an upper or lower limb to induce brief episodes of nonlethal ischemia and reperfusion (remote ischemic conditioning), a finding that has greatly facilitated the translation of ischemic conditioning to various clinical settings. In addition to mechanical approaches, elucidation of the signal-transduction pathways underlying ischemic conditioning has identified several novel targets for pharmacological conditioning. This Review highlights findings from proof-of-concept clinical studies conducted in the past 5–6 years, in which the therapeutic potential of ischemic and pharmacological conditioning has been realized. Large, randomized, controlled trials are now required to determine whether pharmacological and ischemic conditioning improve clinical end points and outcomes in patients with CHD.

Key Points

  • Ischemic conditioning describes an endogenous phenomenon, in which one or more brief episodes of nonlethal ischemia and reperfusion confer protection against a sustained lethal episode of ischemia and reperfusion

  • The conditioning stimulus can be applied before (ischemic preconditioning) or after the onset of (ischemic perconditioning) ischemia, or at the transition from sustained ischemia to reperfusion (ischemic postconditioning)

  • The conditioning stimulus can, moreover, be applied either directly to the heart or to a distant organ or tissue, such as a limb (remote ischemic conditioning)

  • Elucidation of the mechanistic pathways underlying ischemic conditioning has identified potential pharmacological cardioprotective strategies (pharmacological conditioning), which have been largely unsuccessful in the clinical setting

  • Proof-of-concept studies reported benefits with ischemic perconditioning, postconditioning, and remote ischemic conditioning in patients with acute myocardial infarction, and those undergoing cardiac surgery or percutaneous coronary intervention

  • Large, multicenter, randomized, placebo-controlled, clinical trials are now required to determine whether ischemic conditioning can improve clinical outcomes in patients with coronary heart disease

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Figure 1: Timeline showing the slow translation of the results of animal studies of ischemic conditioning to the clinic.
Figure 2: The timing of ischemic conditioning in relation to ischemia–reperfusion injury.

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References

  1. Braunwald, E. & Kloner, R. A. Myocardial reperfusion: a double-edged sword? J. Clin. Invest 76, 1713–1719 (1985).

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Yellon, D. M. & Hausenloy, D. J. Myocardial reperfusion injury. N. Engl. J Med. 357, 1121–1135 (2007).

    CAS  PubMed  Google Scholar 

  3. Murry, C. E., Jennings, R. B. & Reimer, K. A. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 74, 1124–1136 (1986).

    CAS  PubMed  Google Scholar 

  4. Schulz, R., Cohen, M. V., Behrends, M., Downey, J. M. & Heusch, G. Signal transduction of ischemic preconditioning. Cardiovasc. Res. 52, 181–198 (2001).

    CAS  PubMed  Google Scholar 

  5. Yellon, D. M. & Downey, J. M. Preconditioning the myocardium: from cellular physiology to clinical cardiology. Physiol. Rev. 83, 1113–1151 (2003).

    CAS  PubMed  Google Scholar 

  6. Downey, J. M., Davis, A. M. & Cohen, M. V. Signaling pathways in ischemic preconditioning. Heart Fail. Rev. 12, 181–188 (2007).

    CAS  PubMed  Google Scholar 

  7. Ovize, M. et al. Postconditioning and protection from reperfusion injury: where do we stand? Position paper from the Working Group of Cellular Biology of the Heart of the European Society of Cardiology. Cardiovasc. Res. 87, 406–423 (2010).

    CAS  PubMed  Google Scholar 

  8. Heusch, G. Postconditioning: old wine in a new bottle? J. Am. Coll. Cardiol. 44, 1111–1112 (2004).

    PubMed  Google Scholar 

  9. Heusch, G., Boengler, K. & Schulz, R. Cardioprotection: nitric oxide, protein kinases, and mitochondria. Circulation 118, 1915–1919 (2008).

    PubMed  Google Scholar 

  10. Hausenloy, D. J. Signalling pathways in ischaemic postconditioning. Thromb. Haemost. 101, 626–634 (2009).

    CAS  PubMed  Google Scholar 

  11. Hausenloy, D. J. & Yellon, D. M. Remote ischaemic preconditioning: underlying mechanisms and clinical application. Cardiovasc Res. 79, 377–386 (2008).

    CAS  PubMed  Google Scholar 

  12. Hausenloy, D. J. & Yellon, D. M. The second window of preconditioning (SWOP) where are we now? Cardiovasc. Drugs Ther. 24, 235–254 (2010).

    PubMed  Google Scholar 

  13. Gülker, H., Krämer, B., Stephan, K. & Meesmann, W. Changes in ventricular fibrillation threshold during repeated short-term coronary occlusion and release. Basic Res. Cardiol. 72, 547–562 (1977).

    PubMed  Google Scholar 

  14. Marber, M. S., Latchman, D. S., Walker, J. M. & Yellon, D. M. Cardiac stress protein elevation 24 hours after brief ischemia or heat stress is associated with resistance to myocardial infarction. Circulation 88, 1264–1272 (1993).

    CAS  PubMed  Google Scholar 

  15. Kuzuya, T. et al. Delayed effects of sublethal ischemia on the acquisition of tolerance to ischemia. Circ. Res. 72, 1293–1299 (1993).

    CAS  PubMed  Google Scholar 

  16. Przyklenk, K., Bauer, B., Ovize, M., Kloner, R. A. & Whittaker, P. Regional ischemic 'preconditioning' protects remote virgin myocardium from subsequent sustained coronary occlusion. Circulation 87, 893–899 (1993).

    CAS  PubMed  Google Scholar 

  17. Gho, B. C., Schoemaker, R. G., van den Doel, M. A., Duncker, D. J. & Verdouw, P. D. Myocardial protection by brief ischemia in noncardiac tissue. Circulation 94, 2193–2200 (1996).

    CAS  PubMed  Google Scholar 

  18. Birnbaum, Y., Hale, S. L. & Kloner, R. A. Ischemic preconditioning at a distance: reduction of myocardial infarct size by partial reduction of blood supply combined with rapid stimulation of the gastrocnemius muscle in the rabbit. Circulation 96, 1641–1646 (1997).

    CAS  PubMed  Google Scholar 

  19. Kharbanda, R. K. et al. Transient limb ischemia induces remote ischemic preconditioning in vivo. Circulation 106, 2881–2883 (2002).

    CAS  PubMed  Google Scholar 

  20. Schmidt, M. R. et al. Intermittent peripheral tissue ischemia during coronary ischemia reduces myocardial infarction through a KATP-dependent mechanism: first demonstration of remote ischemic perconditioning. Am. J. Physiol. Heart Circ. Physiol. 292, H1883–H1890 (2007).

    CAS  PubMed  Google Scholar 

  21. Andreka, G. et al. Remote ischaemic postconditioning protects the heart during acute myocardial infarction in pigs. Heart 93, 749–752 (2007).

    PubMed  PubMed Central  Google Scholar 

  22. Heusch, G. & Schulz, R. Remote preconditioning. J. Mol. Cell Cardiol. 34, 1279–1281 (2002).

    CAS  PubMed  Google Scholar 

  23. Lim, S. Y., Yellon, D. M. & Hausenloy, D. J. The neural and humoral pathways in remote limb ischemic preconditioning. Basic Res. Cardiol. 105, 651–655 (2010).

    PubMed  Google Scholar 

  24. Na, H. S. et al. Ventricular premature beat-driven intermittent restoration of coronary blood flow reduces the incidence of reperfusion-induced ventricular fibrillation in a cat model of regional ischemia. Am. Heart J. 132 (Pt 1), 78–83 (1996).

    CAS  PubMed  Google Scholar 

  25. Zhao, Z. Q. et al. Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning. Am. J. Physiol. Heart Circ. Physiol. 285, H579–H588 (2003).

    CAS  PubMed  Google Scholar 

  26. Yellon, D. M. & Opie, L. H. Postconditioning for protection of the infarcting heart. Lancet 367, 456–458 (2006).

    PubMed  Google Scholar 

  27. Staat, P. et al. Postconditioning the human heart. Circulation 112, 2143–2148 (2005).

    PubMed  Google Scholar 

  28. Botker, H. E. 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. Lancet 375, 727–734 (2010).

    PubMed  Google Scholar 

  29. Sörensson, P. et al. Effect of postconditioning on infarct size in patients with ST elevation myocardial infarction. Heart 96, 1710–1715 (2010).

    PubMed  Google Scholar 

  30. Hausenloy, D. J. et al. Translating novel strategies for cardioprotection: the Hatter Workshop Recommendations. Basic Res. Cardiol. 105, 677–686 (2010).

    PubMed  PubMed Central  Google Scholar 

  31. Thibault, H. et al. Long-term benefit of postconditioning. Circulation 117, 1037–1044 (2008).

    CAS  PubMed  Google Scholar 

  32. Limalanathan, S. et al. Rationale and design of the POSTEMI (postconditioning in ST-elevation myocardial infarction) study. Cardiology 116, 103–109 (2010).

    PubMed  Google Scholar 

  33. Tarantini, G. et al. Design and methodologies of the POSTconditioning during coronary angioplasty in acute myocardial infarction (POST-AMI) trial. Cardiology 116, 110–116 (2010).

    PubMed  Google Scholar 

  34. Rentoukas, I. et al. Cardioprotective role of remote ischemic periconditioning in primary percutaneous coronary intervention: enhancement by opioid action. JACC Cardiovasc. Interv. 3, 49–55 (2010).

    PubMed  Google Scholar 

  35. Selvanayagam, J. B., Searle, N., Neubauer, S. & Taggart, D. P. Correlation of coronary artery bypass surgery-related myonecrosis with grafted vessel calibre: insights from cardiovascular magnetic resonance imaging. Heart 92, 1329–1330 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Brener, S. J., Lytle, B. W., Schneider, J. P., Ellis, S. G. & Topol, E. J. Association between CK-MB elevation after percutaneous or surgical revascularization and three-year mortality. J. Am. Coll. Cardiol. 40, 1961–1967 (2002).

    CAS  PubMed  Google Scholar 

  37. Fellahi, J. L. et al. Short- and long-term prognostic value of postoperative cardiac troponin I concentration in patients undergoing coronary artery bypass grafting. Anesthesiology 99, 270–274 (2003).

    CAS  PubMed  Google Scholar 

  38. Lehrke, S. et al. Cardiac troponin T for prediction of short- and long-term morbidity and mortality after elective open heart surgery. Clin. Chem. 50, 1560–1567 (2004).

    CAS  PubMed  Google Scholar 

  39. Croal, B. L. et al. Relationship between postoperative cardiac troponin I levels and outcome of cardiac surgery. Circulation 114, 1468–1475 (2006).

    CAS  PubMed  Google Scholar 

  40. Venugopal, V., Ludman, A., Yellon, D. M. & Hausenloy, D. J. 'Conditioning' the heart during surgery. Eur. J. Cardiothorac. Surg. 35, 977–987 (2009).

    PubMed  Google Scholar 

  41. Heusch, G. et al. Coronary microembolization: from bedside to bench and back to bedside. Circulation 120, 1822–1836 (2009).

    PubMed  Google Scholar 

  42. Yellon, D. M., Alkhulaifi, A. M. & Pugsley, W. B. Preconditioning the human myocardium. Lancet 342, 276–277 (1993).

    CAS  PubMed  Google Scholar 

  43. Jenkins, D. P. et al. Ischaemic preconditioning reduces troponin T release in patients undergoing coronary artery bypass surgery. Heart 77, 314–318 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Walsh, S. R. et al. Ischaemic preconditioning during cardiac surgery: systematic review and meta-analysis of perioperative outcomes in randomised clinical trials. Eur. J. Cardiothorac. Surg. 34, 985–994 (2008).

    PubMed  Google Scholar 

  45. Cheung, M. M. et al. Randomized controlled trial of the effects of remote ischemic preconditioning on children undergoing cardiac surgery: first clinical application in humans. J. Am. Coll. Cardiol. 47, 2277–2282 (2006).

    PubMed  Google Scholar 

  46. Günaydin, B. et al. Does remote organ ischaemia trigger cardiac preconditioning during coronary artery surgery? Pharmacol. Res. 41, 493–496 (2000).

    PubMed  Google Scholar 

  47. Hausenloy, D. J. et al. Effect of remote ischaemic preconditioning on myocardial injury in patients undergoing coronary artery bypass graft surgery: a randomised controlled trial. Lancet 370, 575–579 (2007).

    PubMed  Google Scholar 

  48. Rahman, I. A. et al. Remote ischemic preconditioning in human coronary artery bypass surgery: from promise to disappointment? Circulation 122 (Suppl.), S53–S59 (2010).

    PubMed  Google Scholar 

  49. US National Library of Medicine. ClinicalTrials.gov. Effect of Remote Ischaemic Preconditioning on Clinical Outcomes in CABG Surgery (ERICCA), [online]. (2010).

  50. US National Library of Medicine. ClinicalTrials.gov. Remote Ischaemic Preconditioning for Heart Surgery (RIPHeart-Study), [online]. (2010).

  51. Luo, W., Li, B., Lin, G. & Huang, R. Postconditioning in cardiac surgery for tetralogy of Fallot. J. Thorac. Cardiovasc. Surg. 133, 1373–1374 (2007).

    PubMed  Google Scholar 

  52. Li, B., Chen, R., Huang, R. & Luo, W. Clinical benefit of cardiac ischemic postconditioning in corrections of tetralogy of Fallot. Interact. Cardiovasc. Thorac. Surg. 8, 17–21 (2009).

    PubMed  Google Scholar 

  53. Luo, W., Li, B., Chen, R., Huang, R. & Lin, G. Effect of ischemic postconditioning in adult valve replacement. Eur. J. Cardiothorac. Surg. 33, 203–208 (2008).

    PubMed  Google Scholar 

  54. Cavallini, C. et al. Impact of the elevation of biochemical markers of myocardial damage on long-term mortality after percutaneous coronary intervention: results of the CK-MB and PCI study. Eur. Heart J. 26, 1494–1498 (2005).

    PubMed  Google Scholar 

  55. Selvanayagam, J. B. et al. Troponin elevation after percutaneous coronary intervention directly represents the extent of irreversible myocardial injury: insights from cardiovascular magnetic resonance imaging. Circulation 111, 1027–1032 (2005).

    CAS  PubMed  Google Scholar 

  56. Babu, G. G., Walker, J. M., Yellon, D. M. & Hausenloy, D. J. Peri-procedural myocardial injury during percutaneous coronary intervention: an important target for cardioprotection. Eur. Heart J. 32, 23–31 (2011).

    CAS  PubMed  Google Scholar 

  57. Shimizu, M., Konstantinov, E. G., Kharbanda, R. K., Cheung, M. H. & Redington, A. N. Effects of intermittent lower limb ischaemia on coronary blood flow and coronary resistance in pigs. Acta Physiol. (Oxf.) 190, 103–109 (2007).

    CAS  Google Scholar 

  58. Zhou, K. et al. Effects of remote ischemic preconditioning on the flow pattern of the left anterior descending coronary artery in normal subjects. Int. J. Cardiol. 122, 250–251 (2007).

    PubMed  Google Scholar 

  59. Hoole, S. P. et al. Remote ischemic preconditioning stimulus does not reduce microvascular resistance or improve myocardial blood flow in patients undergoing elective percutaneous coronary intervention. Angiology 60, 403–411 (2009).

    PubMed  Google Scholar 

  60. Iliodromitis, E. K. et al. Increased C reactive protein and cardiac enzyme levels after coronary stent implantation. Is there protection by remote ischaemic preconditioning? Heart 92, 1821–1826 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Hoole, S. P. et al. Cardiac Remote Ischemic Preconditioning in Coronary Stenting (CRISP Stent) Study: a prospective, randomized control trial. Circulation 119, 820–827 (2009).

    PubMed  Google Scholar 

  62. Piot, C. et al. Effect of cyclosporine on reperfusion injury in acute myocardial infarction. N. Engl. J. Med. 359, 473–481 (2008).

    CAS  PubMed  Google Scholar 

  63. Mewton, N. et al. Effect of cyclosporine on left ventricular remodeling after reperfused myocardial infarction. J. Am. Coll. Cardiol. 55, 1200–1205 (2010).

    CAS  PubMed  Google Scholar 

  64. Bolli, R. et al. Myocardial protection at a crossroads: the need for translation into clinical therapy. Circ. Res. 95, 125–134 (2004).

    CAS  PubMed  Google Scholar 

  65. Kloner, R. A. & Rezkalla, S. H. Cardiac protection during acute myocardial infarction: where do we stand in 2004? J. Am. Coll. Cardiol. 44, 276–286 (2004).

    PubMed  Google Scholar 

  66. Downey, J. M. & Cohen, M. V. Why do we still not have cardioprotective drugs? Circ. J. 73, 1171–1177 (2009).

    PubMed  Google Scholar 

  67. Ludman, A. J., Yellon, D. M. & Hausenloy, D. J. Cardiac preconditioning for ischaemia: lost in translation. Dis. Model. Mech. 3, 35–38 (2010).

    PubMed  Google Scholar 

  68. Ferdinandy, P., Schulz, R. & Baxter, G. F. Interaction of cardiovascular risk factors with myocardial ischemia/reperfusion injury, preconditioning, and postconditioning. Pharmacol. Rev. 59, 418–458 (2007).

    CAS  PubMed  Google Scholar 

  69. Ali, Z. A. et al. Remote ischemic preconditioning reduces myocardial and renal injury after elective abdominal aortic aneurysm repair: a randomized controlled trial. Circulation 116 (Suppl.), I98–I105 (2007).

    PubMed  Google Scholar 

  70. Venugopal, V. et al. Remote ischaemic preconditioning reduces myocardial injury in patients undergoing cardiac surgery with cold-blood cardioplegia: a randomised controlled trial. Heart 95, 1567–1571 (2009).

    CAS  PubMed  Google Scholar 

  71. Hu, S. et al. Effects of remote ischemic preconditioning on biochemical markers and neurologic outcomes in patients undergoing elective cervical decompression surgery: a prospective randomized controlled trial. J. Neurosurg. Anesthesiol. 22, 46–52 (2010).

    PubMed  Google Scholar 

  72. Jean-St-Michel, E. et al. Remote preconditioning improves maximal performance in highly-trained athletes. Med. Sci. Sports Exerc. doi:10.1249/MSS.0b013e318206845d.

    Google Scholar 

  73. Zhou, W. et al. Limb ischemic preconditioning reduces heart and lung injury after an open heart operation in infants. Pediatr. Cardiol. 31, 22–29 (2010).

    CAS  PubMed  Google Scholar 

  74. Thielmann, M. et al. Remote ischemic preconditioning reduces myocardial injury after coronary artery bypass surgery with crystalloid cardioplegic arrest. Basic Res. Cardiol. 105, 657–664 (2010).

    CAS  PubMed  Google Scholar 

  75. Wagner, R. et al. Myocardial injury is decreased by late remote ischaemic preconditioning and aggravated by tramadol in patients undergoing cardiac surgery: a randomised controlled trial. Interact. Cardiovasc. Thorac. Surg. 11, 758–762 (2010).

    PubMed  Google Scholar 

  76. Hong, D. M. et al. The effect of remote ischaemic preconditioning on myocardial injury in patients undergoing off-pump coronary artery bypass graft surgery. Anaesth. Intensive Care 38, 924–929 (2010).

    CAS  PubMed  Google Scholar 

  77. Ali, N., Rizwi, F., Iqbal, A. & Rashid, A. Induced remote ischemic pre-conditioning on ischemia–reperfusion injury in patients undergoing coronary artery bypass. J. Coll. Physicians Surg. Pak. 20, 427–431 (2010).

    PubMed  Google Scholar 

  78. Laskey, W. K. Brief repetitive balloon occlusions enhance reperfusion during percutaneous coronary intervention for acute myocardial infarction: a pilot study. Catheter. Cardiovasc. Interv. 65, 361–367 (2005).

    PubMed  Google Scholar 

  79. Ma, X., Zhang, X., Li, C. & Luo, M. Effect of postconditioning on coronary blood flow velocity and endothelial function and LV recovery after myocardial infarction. J. Interv. Cardiol. 19, 367–375 (2006).

    PubMed  Google Scholar 

  80. Yang, X. C. et al. Reduction in myocardial infarct size by postconditioning in patients after percutaneous coronary intervention. J. Invasive Cardiol. 19, 424–430 (2007).

    PubMed  Google Scholar 

  81. Laskey, W. K., Yoon, S., Calzada, N. & Ricciardi, M. J. Concordant improvements in coronary flow reserve and ST-segment resolution during percutaneous coronary intervention for acute myocardial infarction: a benefit of postconditioning. Catheter. Cardiovasc. Interv. 72, 212–220 (2008).

    PubMed  Google Scholar 

  82. Zhao, W. S. et al. A 60-s postconditioning protocol by percutaneous coronary intervention inhibits myocardial apoptosis in patients with acute myocardial infarction. Apoptosis 14, 1204–1211 (2009).

    PubMed  Google Scholar 

  83. Xue, F. et al. Postconditioning the human heart in percutaneous coronary intervention. Clin. Cardiol. 33, 439–444 (2010).

    PubMed  PubMed Central  Google Scholar 

  84. Lin, X. M. et al. Attenuation of tumor necrosis factor-α elevation and improved heart function by postconditioning for 60 seconds in patients with acute myocardial infarction. Chin. Med. J. (Engl.) 123, 1833–1839 (2010).

    CAS  Google Scholar 

  85. Lønborg, J. et al. Cardioprotective effects of ischemic postconditioning in patients treated with primary percutaneous coronary intervention, evaluated by magnetic resonance. Circ. Cardiovasc. Interv. 3, 34–41 (2010).

    PubMed  Google Scholar 

  86. Garcia, S. et al. Long-term follow-up of patients undergoing postconditioning during ST-elevation myocardial infarction. J. Cardiovasc. Transl. Res. 4, 92–98 (2011).

    PubMed  Google Scholar 

  87. Fan, Q. et al. Postconditioning attenuates myocardial injury by reducing nitro-oxidative stress in vivo in rats and in humans. Clin. Sci. (Lond.) 120, 251–261 (2010).

    Google Scholar 

  88. Voors, A. A. et al. A single dose of erythropoietin in ST-elevation myocardial infarction. Eur. Heart J. 31, 2593–2600 (2010).

    CAS  PubMed  Google Scholar 

  89. Lipsic, E. et al. A single bolus of a long-acting erythropoietin analogue darbepoetin alfa in patients with acute myocardial infarction: a randomized feasibility and safety study. Cardiovasc. Drugs Ther. 20, 135–141 (2006).

    CAS  PubMed  Google Scholar 

  90. Ozawa, T. et al. Single-dose intravenous administration of recombinant human erythropoietin is a promising treatment for patients with acute myocardial infarction —randomized controlled pilot trial of EPO/AMI-1 study. Circ. J. 74, 1415–1423 (2010).

    CAS  PubMed  Google Scholar 

  91. Taniguchi, N. et al. Erythropoietin prevention trial of coronary restenosis and cardiac remodeling after ST-elevated acute myocardial infarction (EPOC-AMI): a pilot, randomized, placebo-controlled study. Circ. J. 74, 2365–2371 (2010).

    PubMed  Google Scholar 

  92. Ott, I. et al. Erythropoietin in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: a randomized, double-blind trial. Circ. Cardiovasc. Interv. 3, 408–413 (2010).

    CAS  PubMed  Google Scholar 

  93. Najjar, S. S. et al. Intravenous erythropoietin in patients with ST-segment elevation myocardial infarction: REVEAL: a randomized clinical trial. JAMA 305, 1863–1872 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Nikolaidis, L. A. et al. Effects of glucagon-like peptide-1 in patients with acute myocardial infarction and left ventricular dysfunction after successful reperfusion. Circulation 109, 962–965 (2004).

    CAS  PubMed  Google Scholar 

  95. Kitakaze, M. et al. Human atrial natriuretic peptide and nicorandil as adjuncts to reperfusion treatment for acute myocardial infarction (J-WIND): two randomised trials. Lancet 370, 1483–1493 (2007).

    CAS  PubMed  Google Scholar 

  96. Direct Inhibition of δ-Protein Kinase C Enzyme to Limit Total Infarct Size in Acute Myocardial Infarction (DELTA MI) Investigators et al. Intracoronary KAI-9803 as an adjunct to primary percutaneous coronary intervention for acute ST-segment elevation myocardial infarction. Circulation 117, 886–896 (2008).

  97. Kim, J. S. et al. Efficacy of high-dose atorvastatin loading before primary percutaneous coronary intervention in ST-segment elevation myocardial infarction: the STATIN STEMI trial. JACC Cardiovasc. Interv. 3, 332–339 (2010).

    PubMed  Google Scholar 

  98. Ferrario, M. et al. High-dose erythropoietin in patients with acute myocardial infarction: a pilot, randomised, placebo-controlled study. Int. J. Cardiol. 147, 124–131 (2011).

    PubMed  Google Scholar 

  99. Suh, J. W. et al. The effect of intravenous administration of erythropoietin on the infarct size in primary percutaneous coronary intervention. Int. J. Cardiol. 149, 216–220 (2011).

    PubMed  Google Scholar 

  100. US National Library of Medicine. ClinicalTrials.gov. Safety and Efficacy Study of KAI-9803 to Treat Subjects With ST Elevation Myocardial Infarction [Heart Attack] (PROTECTION AMI), [online]. (2011).

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Acknowledgements

D. J. Hausenloy's research is funded by the British Heart Foundation (FS/10/039/28270). His work was undertaken at University College London Hospital/University College London, which received a portion of funding from the UK Department of Health's NIH Research Biomedical Research Center's funding scheme.

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  1. The Hatter Cardiovascular Institute, University College London Hospital, 67 Chenies Mews, WC1E 6HX, London, UK

    Derek J. Hausenloy & Derek M. Yellon

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Hausenloy, D., Yellon, D. The therapeutic potential of ischemic conditioning: an update. Nat Rev Cardiol 8, 619–629 (2011). https://doi.org/10.1038/nrcardio.2011.85

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